COVID-19 quarantine affects HDP patients.

Since the extreme acute breathing syndrome coronavirus 2 (SARS-CoV-2, COVID-19) changed into first suggested in Wuhan, China, in December 2019, it has hastily swept the global and brought tremendous morbidity and mortality to all humanity. Worse still, the continual generation of new versions has led to wider transmissibility, in particular model B.1.617.2 (Delta), most appropriate to the current wave of irritation ravaging the Indian and turning into the dominant lineage in the United Kingdom.1 The exponential growth of COVID-19 situations has forced many governments to impose a strict home quarantine.2 This without difficulty slows down the common of the contagion, fighting the collapse of fitness care systems. Whereas the home quarantine measures have affected the commonplace health of the population, including intellectual fitness, sleep, weight, dietary habits, and even a few chronic diseases.3–7
However, limited guidance is reachable about how domestic quarantine affects the fitness and consequences of pregnant ladies, in certain for patients with pregnancy complications.

Hypertensive disorders of pregnancy (HDP), including chronic hypertension, gestational hypertension (GH), preeclampsia (PE)/eclampsia (E), and PE/E editions superimposed on chronic top blood pressure, constitute one of the most appropriate reasons of maternal and perinatal mortality worldwide. Moreover, a history of HDP will lead to an elevated chance of clinical cardiovascular disease (CVD) or other chronic stipulations in the destiny.8 The population-based mostly cohort studies found out that obesity and extreme weight benefit all through pregnancy were big contributors to the higher hazards of HDP, specifically for PE/E, and are associated with plenty of bad maternal and neonatal outcomes.9,10 Other risk factors were also said to be associated with the increased prevalence of PE/E, such as pregnant with older maternal age, multifetal pregnancy, and primiparity.11 Cohort studies showed that both GH and PE might be more universal in gravidas with greater insulin resistance, and the arrangement of gestational glucose intolerance with GH appears to be in element explained through insulin resistance and vascular dysplasia. Thus, nondiabetic girls who have PE are more likely to develop gestational diabetes (GDM) right through pregnancy.12 In addition, women with GDM have an greater possibility of PE, particularly in the early stages, as indicated in the latest ISSHP.thirteen20,21 HDP complicated with GDM will bring more necessary unfavorable pregnancy results, so paying attention to this form of top-possibility population and studying its risk elements deserve to be one of the focuses of future analysis.14 Meanwhile, some of these chance elements rose significantly throughout the COVID-19 quarantine. Home quarantine made people more inclined to overeating and intake of high-calorie food.15 Adopting usual physical sport all through pregnancy will advantage either mother and fetus, including attenuation of HDP, superior cardiovascular function, and limited pregnancy weight gain;16 conversely, a sedentary lifestyle can also lead to the deterioration of HDP.17 Home quarantine limits physical sport, making sedentary day-to-day life.18 In addition, pregnant girls with tension also can contribute to the greater occurrence of HDP.19 Current experiences confirmed that the standard population suffers from expanding intellectual stress and anxiety all over the COVID-19 quarantine.20,21
This look at aimed to ascertain whether domestic quarantine affects pregnant women with HDP and HDP patients complex with GDM. We investigated the clinical signals and pregnancy consequences of HDP patients who had experienced a strict home quarantine for at least one month throughout the three-month from 24 January 2020 to 20 April 2020 in Chongqing, China, and also covered advice on patients without home quarantine during the same duration of 2019 and 2018.

Therefore, the existing research attempts to supply evidence so that governments and hospitals can plan constructive approach to life regulate and prenatal care.
Materials and Methods
Ethics Approval
This examine changed into authorized by way of the ethics committee of the First Affiliated Hospital of Chongqing Medical University (ID: 20200501).

To give coverage to the privacy of patients, the non-public identification advice of all cases become deleted, and all data received turned into kept anonymized.
Study Design and Participants
The latest study was a single-center retrospective cohort diagnosis of archives collected in the First Affiliated Hospital of Chongqing Medical University, a large finished coaching clinic with 10,000 births in keeping with year. Our fundamental objective become to exhibit the outcomes of home quarantine exposure on pregnancy consequences in patients with HDP, including gestational hypertension (GH) and preeclampsia/eclampsia (PE/E).

Therefore, the cohort protected the GH patients and PE/E patients who experienced at least one month of home quarantine all through the outbreak of COVID-19 in 2020, as neatly as the patients in the comparable duration of 2019 and 2018 who were without home quarantine. Given the strict home quarantine in Chongqing, China, which levels from 24 January 2020 to 20 April 2020, we inferred that the patients who bring among 24 February 2020 to 24 November 2020 have a history of domestic quarantine for at least one month, according to their gestational weeks. Exclusion criteria were without prime blood force, chronic hypertension, and other chronic Medical stipulations apart from for GDM or the patients with incomplete clinical tips.

Additionally, the patients in 2020 diagnosed with COVID-19 by RT-PCR and clinical signs were excluded.
All participants strictly followed the diagnostic criterion, “the HDP: ISSHP category, diagnosis, and management strategies for overseas practice”, that GH become explained as systolic blood pressure (BP) ≥ 140 and/or diastolic BP ≥ 90 mm Hg arising de novo at ≥ 20 weeks’ gestation in the absence of proteinuria or other findings suggestive of PE.22 PE (de novo) is gestational hypertension followed by way of one or more of the following new-onset stipulations at ≥ 20 weeks’ gestation according to the existing ISSHP (2021): 1) proteinuria, 2) other maternal end-organ dysfunction, including neurological headaches, pulmonary edema, hematological complications or liver involvement, 3) uteroplacental dysfunction.
Additionally, patients with GH or PE/E complicated with gestational diabetes (GDM) were also blanketed in our study.

All participants were introduced a 75 g oral glucose tolerance examine (OGTT) after 8–10 h of overnight fasting all over the antenatal examination in early pregnancy and the time is in the past 24 weeks. With GDM diagnosed from venous samples according to the clinical guideline, IADPSG/WHO 2010 criteria (fasting plasma glucose ≥ 5.1 mmol/L, 1 h plasma glucose ≥ 10.0 mmol/L or 2 h plasma glucose ≥ 8.5 mmol/L), and at least one glucose threshold cost must be equaled or exceeded to outline the patient as having gestational diabetes.23 Pregnant effects were divided into maternal effects and neonatal consequences.

Maternal consequences contain delivery mode, Diastolic Pressure (DP), Systolic Pressure (SP), blood platelet, and uric acid. Fetal outcomes included neonatal weight, abdominal circumference, head circumference, body duration, placental weight, thickness, duration, width, one-minute Apgar rankings, and the associated obstetrical complications such as placental elements, umbilical elements, Fetal growth restrict (FGR), and premature beginning.

Data Collection
All documents were amassed from the health facility electronic scientific information (EMR) database, adding classic maternal information, pregnancy effects, and neonatal consequences.

Statistical Analyses
During records diagnosis, Chi-square or Fisher’s accurate examine was used for specific variables, adding the occurrence of GH and PE/E.

The population characteristics were conducted to examine for adjustments between the home quarantine neighborhood and both control group.

Continuous variables with ordinary distribution were provided as mean ± SD, including age, gestational age, and gestational weight gain.

The median plus 25–75 interquartile variety (IQR) become used to reveal non-normally distributed variables, such as parity, gravidity, and fetal number. Additionally, specific variables were presented as percentages and counts, including pre-pregnancy BMI and BMI after pregnancy. The P-values were acquired by means of one-way analysis variance that turned into used to compare continuous variables in the traditional characteristics of the pregnant lady in alternative corporations, while the Mann–Whitney verify for categorical variables. The L-S-D correction outcomes were used to post hoc analysis of pairwise comparisons and indicated the huge alterations between the two agencies in Tables 1 and 2.

Table 1 Sociodemographic and Obstetric Histories of Patients with HDP
Table 2 Sociodemographic and Obstetric Histories of Patients with HDP-GDM
We conducted extra diagnosis on the effects of pregnant ladies and neonates. The obstetrical headaches were analyzed by means of Logistic regression and offered as odds ratios (OR).

In the look at of HDP patients, distinctive logistic regression become used to eliminate confounding elements, adding parity and gestational weight advantage, and adjusted odds ratios (AOR) were used as the results.

The regression models for HDP complicated with GDM patients were adjusted according to the expertise confounding outcomes of age, parity, and gestational weight gain, and offered as adjusted odds ratios (AOR).

Significant analysis become performed on pregnant women-related signals, adding delivery pattern, OGTT biochemical criterion, HP, DP, blood platelet, and uric acid criterion.
In addition, huge analysis changed into conducted on the neonatal index, adding neonatal weight, frame length, placental weight, length, weight, thickness, and length.

Furthermore, obstetric headaches of neonatal consequences in various companies were also used logistic regression, such as placental implantation, umbilical cord wrap, fetal boom limit, and untimely birth.

No more than 5% of values overlooked in the variables used in the statistical analyses. Therefore, none of the imputations were performed for the lacking files.

All analyses were conducted using Statistical Package for the Social Sciences 22.0 (SPSS 22.0, IBM Corporation, Chicago, IL, USA) software.
Clinical Characteristics of HDP Patients in 2018, 2019, and 2020
The whole number of women added in the research middle changed into 6166 in 2020, 7268 in 2019, and 7153 in 2018.

After screening the electronic medical data according to the above inclusion and exclusion criteria, 6024 girls were excluded in 2020, 7194 in 2019, and 7093 in 2018.

Finally, a whole of 276 women with HDP were used for next analysis, adding 142 women with HDP with COVID-19 quarantine history in 2020, 74 in 2019, and 60 in 2018.

The prognosis of HDP incidence in three years showed that the HDP incidence expense in 2020 transformed into as high as 2.30%, considerably larger than that in 2018 (0.84%) and 2019 (0.51%) (P < 0.001, Figure 1).

Additionally, the incidence of either GH (1.62%) and PE/E (0.68%) in 2020 were higher than that in 2018 (0.45%/0.39%) and 2019 (0.47%/0.55%) (P < 0.001/P = 0.016); the incidence of HDP complex with GDM become also significantly higher in 2020 (P = 0.002).

A further look at of the baseline clinical characteristics of 276 HDP patients showed that gestational weight advantage of patients with HDP in 2020 turned into more than in 2018 and 2019 (2020: 17.16 ± 6.37 kilograms; 2018: 1335 ± 3.51 kilograms; 2019: 14.03 ± 5.87 kilograms; P = 0.031, Table 1).

Body mass index (BMI) became divided into four categories based on the Chinese BMI classification standard, < 18.5 (underweight), 18.5–23.9 (general weight), 24–27.9 (obese), and ≥ 28 (obesity).

The data showed that there was no difference in patients with HDP of four pre-pregnancy BMI categories (P = 0.373); nevertheless, the obesity ratio of patients with HDP higher considerably in 2020 (64.8%) than that in 2018 (40.0%) and 2019 (48.7%) (P = 0.033).

Additionally, the parity of patients with HDP in 2020 become significantly more than patients with HDP in 2018 and 2019 (P < 0.001).

Nevertheless, there is no difference in the number of fetuses among three years.
Figure 1 Total incidence and subsets occurrence of HDP. The complete number of girls added in the research middle turned into 6166 in 2020, 7268 in 2019, and 7153 in 2018.

After screening the electronic medical facts according to the above inclusion and exclusion criteria, 6024 girls were excluded in 2020, 7194 in 2019, and 7093 in 2018.

Finally, a complete of 276 HDP patients were used for next diagnosis, including 142 HDP patients in 2020, 74 in 2019, and 60 in 2018.

Additionally, a whole of 197 women with HDP-GDM were blanketed in our cohort, adding 105 women in 2020, 52 women in 2019, and 40 in 2018.

As for women with GH, there was a hundred women in 2020, 32 girls in 2018 and 34 women in 2019.

Lastly, 42 girls with PE/E in 2020 were enrolled in our cohort, 28 girls in 2018 and 40 women in 2019.

Maternal Outcomes of HDP Patients in 2018, 2019, and 2020
Although the delivery sample of pregnant ladies at all times connected obstetrical cognizance, dissimilar logistic regression showed no difference among the three years (P = 0.406).

Consistent with the above consequences, dissimilar logistic regression also showed that gestational weight advantage of HDP patients in 2018 (AOR: 0.86, 95% CI, 0.76–0.98, P = 0.021) and 2019 (0.89, 95% CI, 0.77–0.98, P = 0.026) became less than 2020.

The biochemistry indexes of HDP patients showed that DP in 2018 (AOR: 4.41, 95% CI, 1.13–17.23, P = 0.033) and SP in 2019 (AOR: 2.80, 95% CI, 1.01–7.71, P = 0.047) were minimize than that in 2020.

Moreover, the uric acid level of patients in 2019 (AOR: 3.50, 95% CI, 1.03–11.87, P = 0.045, Table 3) was minimize than in 2020.

Table 3 Pregnant Outcomes of HDP Patients
Neonatal Outcomes of HDP Patients in 2018, 2019, and 2020
We next studied the effects of domestic quarantine on neonatal consequences, logistic regression prognosis showed that neonatal weight in 2020 changed into cut than that in both 2018 (AOR: 1.11, 95% CI, 1.02–1.32, P = 0.004) and 2019 (AOR: 1.21, 95% CI, 1.10–1.42, P = 0.007).

Furthermore, neonatal abdominal circumference in 2018 was longer (AOR: 1.03, 95% CI, 1.01–1.06, P = 0.004) than 2020; head circumference in both 2018 and 2019 were longer (2018: AOR: 1.05, 95% CI, 1.01–1.10, P = 0.024; 2019: AOR: 1.06, 95% CI, 1.01–1.10, P = 0.010) than 2020; as neatly as longer body duration of 2018 and 2019 (2018: AOR: 1.42, 95% CI, 1.06–1.89, P = 0.017; 2019: AOR: 1.34, 95% CI, 1.04–1.73, P = 0.022, Table 3).

Additionally, the neonatal placenta in 2018 and 2019 become heavier (2018: AOR:1.02, 95% CI,1.01–1.03, P = 0.013; 2019: 1.04,95% CI, 1.02–1.05, P = 0.033) and larger (2018: AOR: 1.92, 95% CI, 1.08–3.42, P = 0.027; 2019: AOR: 1.61, 95% CI, 1.05–2.49, P = 0.031) than that in 2020.

Newborns in 2020 had minimize one-minute Apgar ratings than 2018 (AOR: 0.17, 95% CI, 0.04–0.70, P = 0.015, Table 3).

The exertions issues were additional analyzed to compare the outcomes of home quarantine on fetal effects.

Multivariate logistic regression turned into used to keep watch over for the parity and gestational week. The advice showed that a higher chance of FGR in 2020 than in 2018 and 2019 (2018: AOR: 3.57, 95% CI, 1.16–5.81, P = 0.037; 2019: AOR: 7.88, 95% CI, 1.46–11.93, P = 0.024, Table 3) whether in univariate analysis or after adjusting for covariates.
Clinical Characteristics of HDP Complicated with GDM Patients in 2018, 2019, and 2020
Notably, the information showed that the incidence of HDP complicated with GDM is expanding year by means of year from 2018 to 2020, and more than 70% of the entire 276 HDP patients were complex with GDM, thus making additional diagnosis of maternal and neonatal outcomes of the ones patients. The mean age of HDP complicated with GDM (HDP-GDM) patients in 2020 converted into 30.68 ± 4.13, and they were more youthful as compared to 2018 (2018: 34.90 ± 4.36; 2019: 29.81 ± 5.22; P = 0.015).

Although the gestational weight advantage of HDP-GDM patients in 2020 was more than 2018 and 2019 (2020: 17.13 ± 5.43 kilogram; 2018: 12.75 ± 4.34 kilogram; 2019: 14.21 ± 4.57 kilogram; P = 0.031, Table 2), there turned into no difference among the pre-pregnancy BMI, particularly for the overweight patients (2020: 15.2%; 2018: 10.0%; 2019: 11.5%; P = 0.200).

In contrast, BMI files after pregnancy tested that home quarantine patients have a higher obesity fee than in 2018 and 2019 (2020: 70.4%; 2018: 30.0%; 2019: 50.0%; P = 0.042).

The parity of patients with HDP-GDM in 2020 transformed into significantly more than in 2018 and 2019 (P = 0.001).

However, the number of fetuses within three years is not statistically huge.

Effects of Home Quarantine on Pregnancy Outcomes in HDP Complicated with GDM Patients
While analyzing the maternal results of HDP complicated with GDM patients, only DP and gestational weight advantage had massive adjustments among 2018 and 2020, whereas other indexes, including start mode, blood platelet, uric acid, and OGTT, had no difference among the three years. Logistic regression showed that HDP-GDM patients had lower DP (AOR: 14.64, 95% CI, 1.22–17.64, P = 0.034), SP (AOR: 2.86, 95% CI, 1.10–9.06, P = 0.045) and less gestational weight advantage (AOR: 0.85, 95% CI, O.72–1.00, P = 0.044, Table 4) than 2020.

Table 4 Pregnant Outcomes of HDP with GDM Patients
Logistic regression prognosis showed that neonatal weight of HDP-GDM patients in 2020 was minimize than that in either 2018 (AOR: 1.11, 95% CI, 1.01–1.21, P = 0.048) and 2019 (AOR: 1.12, 95% CI, 1.11–1.13, P = 0.006).

Besides, neonate of HDP-GDM patients in 2019 had longer abdominal circumference (AOR: 1.14, 95% CI, 1.11–1.17, P = 0.032), head circumference (AOR: 1.07, 95% CI, 1.01–1.12, P = 0.015), and body length (AOR: 1.91, 95% CI, 1.21–3.01, P = 0.006) than 2020.

Neonate of HDP-GDM patients in 2020 also had lower one-minute Apgar scores than 2018 and 2019 (2018: AOR: 0.19, 95% CI, 0.10–0.73, P = 0.025; 2019: AOR: 0.20, 95% CI, 0.04–0.94, P = 0.042).

The neonatal placenta in 2018 and 2019 turned into heavier (2018: AOR:1.13, 95% CI,1.11–1.15, P = 0.006; 2019: 1.thirteen95% CI, 1.11–1.15, P = 0.010) than 2020, and greater in size than 2020 (AOR: 2.07, 95% CI, 1.04–4.12, P = 0.039, Table 4).

Similarly, the hard work complications were also blanketed in the analysis to validate the effects of domestic quarantine on HDP-GDM patients. After multivariate logistic regression diagnosis was used to regulate the age, parity, and gestational week, the effects showed that there was a better chance of FGR in 2020 than in 2018 and 2019, whether in multivariate prognosis or after adjusting for covariates (AOR: 4.29, 95% CI, 1.01–10.49, P = 0.049, Table 4), even as the occurrence of other labor problems has not observed any difference.
Lockdown can without problems regulate swift infectious diseases through cutting off the direction of transmission and protecting inclined people, and miraculous effects have been accomplished during the outbreak of cholera or plague.24,25 During the outbreak of COVID-19 and the fresh onslaught of Delta, a more infectious mutant, local governments have been forced to adopt varying tiers and paperwork of home quarantine, which with no trouble curbing the widespread spread of the virus. As a susceptible population to COVID-19, pregnant girls are providers to develop slight or extreme disease once infected, and domestic quarantine has given better protection to those vulnerable groups.26,27 However, home quarantine is a double-edged sword, leading to an increased risk of depression and tension in pregnant women.28 In addition, in give a boost to of conducting the existing examine, we have learned that a variety of risk factors for HDP increased significantly all through domestic quarantine, adding BMI, activity, intellectual health, etc. Therefore, this examine aimed to examine the affects of domestic quarantine on pregnant girls and their pregnancy outcomes throughout the COVID-19 outbreak. Primarily, our results showed a tremendous increase in the prevalence of HDP with a history of home quarantine, including GH, PE/E, and complicated with GDM. This is consistent with the lately stated tremendous increase in the occurrence of a whole lot of pregnancy complications, adding HDP, all over the blockade of the COVID-19 epidemic in Israel.29 Although confirmation from a larger population cohort is still necessary, we speculate that the increased incidence of gestational hypertension led to by means of domestic quarantine may also be common, which deserve to capture the cognizance of the govt, clinical institutions, and pregnant women.

Studies have validated that gestational weight gain and BMI after pregnancy are self sustaining possibility factors for HDP and GDM, and the possibility of early-onset and overdue-onset HDP is progressively increased among women with the increase of the point of obesity.30 More importantly, anxiety and reduced exercise may also also be concerned in the occurrence of HDP as self sustaining possibility elements.

Pregnant ladies can also be more likely to have tension and depression due to concerns approximately working, finance, relationship, or housing problems and other complications during domestic quarantine. These terrible feelings immediate them to overeating and devour more top-fat, top-carbohydrate, and top-energy foods.31,32 Furthermore, overweight and obese patients tended to have top-calorie intake and gained weight frequently. The better BMI changed into also associated to less frequent consumption of vegetables, fruit, and legumes right through home quarantine having said that better adherence to meat, dairy, and quick foods.33 Exercise behavior changed during domestic quarantine additional led to an increase in gestational weight advantage and BMI after pregnancy, which transformed into mainly characterized through reduced activity time, a reduce in undertaking intensity (PA) obviously, and a “sedentary pandemic”.34 Comparatively, inactive americans become less active and spent less time exercising, specially ladies throughout pregnancy.35 Our results discovered that the occurrence of obesity (BMI > 28) and gestational weight advantage in pregnant ladies with HDP in 2020 turned into significantly higher than that in 2018 and 2019, which may also be explained by means of the changes in living habits all over home quarantine. Therefore, we speculated that the worse pregnancy outcomes of HDP patients with a history of domestic quarantine in 2020 than in 2018 and 2019 can even be brought approximately by way of the increased possibility elements.

However, more evidence is obligatory to aid this inference.
Our findings established that the DP of HDP patients in 2020 was considerably greater than that in 2018, and SP turned into significantly higher than that in 2019.

We speculated that 1) “sedentary pandemic” and reduced pastime worsened cardiovascular function, most desirable to the advancement of HDP;16 2) Stress is one of the crucial reasons of cardiovascular disease, in certain hypertension, and the susceptibility of pregnant ladies to force and the greater anxiety and depression considerably greater the possibility and progression of HDP.36 We also discovered higher uric acid levels in HDP patients in 2020.

Studies indicated that uric acid is a chance aspect for prime blood pressure, and increased serum uric acid levels will accelerate prime blood pressure.37 In addition, uric acid is a dependable predictor of PE; prime serum uric acid level may also indicate an greater chance of PE and adverse fetal outcomes, such as fetal distress, FGR, and preterm or perinatal death.38,39
The weight, length, abdominal circumference, head circumference, and APGER ranking of newborns in 2020 were reduce than in 2018 and 2019; meanwhile, the occurrence of FGR higher considerably in 2020.

These implied that the newborns in 2020 had worse development than in 2018 and 2019.

First, GH is associated with an greater possibility of damaging maternal and fetal results, adding preterm birth, FGR, perinatal death, acute renal or liver failure, etc.40 Moreover, extreme gestational weight advantage, Obesity, and PE/E diseases will also lead to damaging maternal and fetal consequences.10,41
In summary, our findings showed that home quarantine would increase the incidence of HDP and lead to destructive maternal and fetal outcomes in HDP patients, including worse biochemical signals in pregnant girls and worse physical condition of the fetus. These also can be explained through the increase of HDP-associated risk elements caused by the changes of approach to life and mental health impairment all over domestic quarantine. Thus, the govt and the hospital need to enhance mental counseling, endeavor guidance, and nutritional management for pregnant ladies and speed up the development of home quarantine guides.
Although the research clarified the impact of home quarantine on HDP patients, it has some limitations. Firstly, the pattern simplest came from a single-center, and the sample length changed into relatively small. Secondly, obtaining quantitative documents on vitamin, recreation, and mental state of HDP patients from the electronic scientific data is hard.
Ethics Approval and Consent to Participate
This study turned into authorized by way of the ethics committee of the First Affiliated Hospital of Chongqing Medical University (ID: 20200501).

All participants offered verbal informed consent, which modified into documented in an Excel file and kept with a safety code. At that particular time in 2020, all sanatorium personnel were busy doing clinical work and had no time to achieve written knowledgeable consent from all participants. In addition, the pregnant ladies in 2018 and 2019 blanketed in our cohort were contacted by telephone and obtained their verbal informed consent. The Ethics Committee also approved the system for verbal informed consent of our look at.

The Ethics Society of Clinical Scientific Research authorized the vacationing and use of the clinical records described in our examine.

All the strategies were conducted following the moral standards of the institutional analysis committee and the 1964 Helsinki declaration and its later amendments.
The authors also thank all involved laboratory technicians for their help with archives selection and analysis.

Author Contributions
All authors made a big contribution to the paintings stated, whether that is in the conception, study design, execution, acquisition of files, diagnosis and interpretation, or in all these areas; took part in drafting, revising or severely reviewing the article; gave final approval of the edition to be published; have agreed on the magazine to which the article has been submitted; and agree to be accountable for all aspects of the paintings.

This work was funded by way of the National Natural Science Foundation of China (grant numbers 81801458 and 81771614).

The authors claim that they have no conflicts of interest in this paintings.


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