Abelmoschi Corolla is extensively applied in managing diabetic nephropathy (DN) and other renal conditions due to its diuretic and detoxifying properties. The primary bioactive constituents of Abelmoschi Corolla are flavonoids, including notably rutin, hyperoside, isoquercitrin, hibifolin, myricetin, quercetin 3-O-β-D-glucuronide, and quercetin. These flavonoid components can influence the pathological progression of DN via a multi-target synergistic mechanism, effectively reducing proteinuria levels. This review examines the roles of Abelmoschi Corolla and its flavonoid components in modulating the key pathological aspects of DN and their underlying mechanisms, and briefly discusses the metabolic patterns of its bioactive components and the research progress in combined medication, aiming to provide a forward-looking scientific foundation for further investigating the molecular mechanisms and clinical applications of Abelmoschi Corolla in DN treatment.

ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.

Objective:To investigate the high risk factors,diagnostic accuracy of ultrasonography and pregnan-cy outcomes of umbilical cord wrapped around the neck for≥4 loops.Methods:The clinical data of 64 pregnant women with umbilical cord around the neck for≥4 loops(the group with umbilical cord around the neck≥4 loops)in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2011 to February 2024 were retrospectively analyzed.At the same time,80 cases with umbilical cord around the neck for 1-2 loops(the group with umbilical cord around the neck 1-2 loops)were randomly selected as the controls.General information,clinical manifestations,ultrasound diagnosis and other data of the two groups were collected.The risk factors of umbilical cord around the neck≥4 loops and diagnostic accuracy of ultrasonography were ana-lyzed with univariate and multivariate Logistic regression analysis,and the pregnancy outcomes were compared between the two groups.Results:①The incidence of pregnancy,abortion,delivery and history of cesarean sec-tion were lower in the group with umbilical cord around the neck ≥4 loops than those in the group with umbilical cord around the neck 1-2 loops.The incidence of consciously abnormal fetal movement,abnormal umbilical ar-tery systolic/diastolic(S/D)ratio,abnormal fetal heart rate monitoring(NST)and fetal distress were higher in the group with umbilical cord around the neck≥4 loops than those in the group with umbilical cord around the neck 1-2 loops,and the differences were statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that polyhydramnios and excessively long cord were independent risk factors for umbilical cord around the neck≥4 loops(OR＞1,P＜0.05).③When the time between ultrasound diagnosis and the operation was 2 days,the consistency rate between ultrasound diagnosis of umbilical cord around the neck≥4 loops and intrao-perative diagnosis was the highest,and the difference was statistically significant with＞3 days(46.2％vs.6.30％,P＜0.05).Compared with umbilical cord around the neck 3 loops,ultrasound diagnosis of umbilical cord loops around the neck at 4 or 5 loops had a higher consistency rate with intraoperative diagnosis,and the differ-ence was statistically significant(P＜0.05).④The incidence of premature delivery,neonatal asphyxia and admis-sion to neonatology in the group with umbilical cord around the neck ≥4 loops were higher than those in the group with umbilical cord around the neck 1-2 loops,and the difference was statistically significant(P＜0.05);and the gestational week and birth weight of newborns were significantly lower(P＜0.05).Conclusions:Polyhydramnios and excessively long cord are high risk factors for umbilical cord around the neck≥4 loops.The closer the ultra-sound diagnosis is to the time before cesarean section and the more times the umbilical cord is around the neck in ultrasonic diagnosis,the higher the diagnostic accuracy.Fetal outcomes with umbilical cord around the neck≥4 loops are worse.