Objective To investigate the relationship between triglyceride-gluscose(TyG)index in early pregnancy and the delivery of small for gestational age infant(SGA)in patients with gestational diabetes mellitus(GDM).Methods A total of 1 532 pregnant women from Shanghai Fifth People's Hospital and the Second People's Hospital of Kashgar Region,who were enrolled in the study between Jan 2018 and Jun 2023 and met the inclusion criteria,were categorized into the group with GDM(754 cases)and the group without GDM(778 cases)based on the results of the oral glucose tolerance test(OGTT)conducted at 24-28 weeks of pregnancy.Within the GDM group,patients were further categorized into 3 groups based on neonatal weight:SGA group,large for gestational age infant(LGA)group,and appropriate for gestational age infant(AGA)group.A Logistic regression model was used to analyze the independent influences on SGA delivery in patients with GDM to analyze the correlation between the TyG index and the occurrence of SGA.The predictive value of the TyG index in early pregnancy for SGA delivery in GDM patients was analyzed using ROC curves.Results The TyG index in the SGA group of GDM patients was significantly lower than that in the LGA,AGA and control without GDM group(P＜0.05).Multifactorial logistic regression analysis revealed that the TyG index was independently correlated with the SGA in GDM patients(P＜0.05).The ROC curve analysis demonstrated a good predictive value of the TyG index in early gestation for SGA delivery in GDM patients(AUC=0.821,95%CI:0.763-0.879,P＜0.001).Conclusion The TyG index in early pregnancy among GDM patients is independently correlated with the occurrence of SGA infants and has a good predictive value for SGA delivery in GDM patients.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
Male ; Humans ; Child ; Disorders of Sex Development/pathology* ; Hypospadias/complications* ; Cryptorchidism/complications* ; Retrospective Studies ; Adrenal Hyperplasia, Congenital ; Steroid 21-Hydroxylase

Aim To explore the effect of androgen receptor AR on the proliferation and lipid synthesis of cardiac fibroblasts under high-glucose conditions and the possible molecular mechanism.Methods The hearts of neonatal rats were dissected for primary culture of cardiac fibroblasts. Then the growth status of CFs was observed under the inverted microscope, and the identification of CFs was performed by immunofluorescence staining using anti-vimentin. After cell adherence, the cells were divided into blank control group, high glucose model group, negative control group, and overexpressed AR group. The glucose concentration was 33.0 mmol·L-1 except that the blank control group was 5.5 mmol·L-1. After 24 hours of CFs culture, Western blot and RT-qPCR were used to detect the expression of AR, FASN, PCNA, cyclin D1, α-SMA, and collagen . Oil red O and CCK-8 were used to detect the changes in lipid synthesis and cell proliferation ability, respectively.Results Compared with the blank control group, the lipid synthesis and proliferation of CFs in the high glucose model group were enhanced. Western blot and RT-qPCR results showed that the expression of AR decreased, while the expression of fat lipid synthase(FASN), proliferation marker PCNA, cyclin D1 and fibrosis marker α-SMA and collagen increased. After AR overexpressed plasmid was transfected into the CFs treated by high glucose, AR overexpression markedly decreased the expression of FASN, PCNA, cyclin D1, α-SMA and collagen compared with the empty plasmid‐transfected group. Meanwhile, oil red O staining and CCK-8 results showed that the lipid synthesis and proliferation ability of the overexpressed AR group decreased compared with the empty vector group, respectively. Conclusions High glucose promotes the proliferation and lipid synthesis of cardiac fibroblasts. Besides, the mechanism may be related to the regulation of lipid synthesis regulated by AR.

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.
Apoptosis ; Kelch-Like ECH-Associated Protein 1/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Plant Extracts ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics*

Objective:To investigate the application value of triangular modal construed for planning approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients who underwent local laparoscopic resection of liver tumors located in superior part of central liver lobe at the Affiliated Hospital of Qingdao University from January to June 2020 were collected. There were 6 males and 4 females, aged from 41 to 63 years, with a median age of 54 years. Preoperative triangular model was constructed for all patients to plan approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe. Observation indicators: (1) preoperative general situations of patients; (2) surgical situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview to detect tumor recurrence and survival of patients up to February 2021. Measurement data with normal distribution were expressed as Mean± SD. Count data were expressed was absolute numbers. Results:(1) Preoperative general situations of patients: hepatocellular carcinoma was found in 7 cases, inthahepatic cholangiocarcinoma was found in 2 cases and ovarian cancer with liver metastasis was found in 1 case. Three cases had tumors located in S4a segment, 2 cases had tumors located in ventral subsegment of S8 segment, 2 cases had tumors located in dorsal subsegment of S8 segment, and 3 cases had tumors across the ventral segment of S4a+S8. The diameter of tumors was (3.4±1.0)cm. (2) Surgical situation: all the 10 patients underwent R 0 resection successfully, with no intraoperative blood transfusion or conversion to open surgery. The operation time of 10 patients was (149±59)minutes, the volume of intraoperative blood loss was (294±163)mL, the minimum surgical margin of specimen was (1.1±0.2)cm. The alanine aminotransferase was (324±151)U/L on the postoperative first day, the aspartic aminotransferase was (401±113)U/L on the postoperative first day, and the duration of postoperative hospital stay was (9±4)days. No bile leakage, hemorr-hage, reoperation or other complications occurred in all patients. (3) Follow-up: 10 patients were followed up for 7?13 months, with a median follow-up time of 11 months. All patients had no margin recurrence or distant metastasis. Conclusion:It is safe and feasible to construct triangular modal for planning approach of local laparoscopic resection of liver tumors located in superior part of central liver lobe.

Objective:To establish an ultra-performance liquid chromatography-mass spectrometry （UPLC-MS/MS） for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration， and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome （CVH-IBS）. Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty （PTCA） balloon stimulation method. After intragastric administration of Wujiwan （0.245 g·kg^-1）， blood was collected from the jugular vein at different time points， and the plasma concentrations of 10 active ingredients （berberine hydrochloride， palmatine hydrochloride， coptisine hydrochloride， jatrorrhizine hydrochloride， epiberberine， dihydroberberine， evodiamine， evodine， paeoniflorin， albiflorin） in Wujiwan was detected simultaneously by UPLC-MS/MS， the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group， the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent， and the peak time （t_max） was prolonged. Among them， the t_max of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute， respectively （P<0.05， P<0.01）. Area under the plasma concentration-time curve （AUC_0-t） of each component increased， and evodiamine and paeoniflorin were significantly different （P<0.05， P<0.01）. The clearance rates （CL/F） of these 10 active ingredients were all decreased， among which berberine hydrochloride， palmatine hydrochloride and evodiamine had significant differences （P<0.05， P<0.01）. Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats， which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.

The non-specific administration of antitumor drugs is the main cause for the side effects of chemotherapy drugs on normal tissues. The application of nanotechnology in the delivery of anti-tumor drugs is one of the important ways to improve the therapeutic effect and to reduce the side effects. The current study aimed to synthesize pH responsive poly (methoxy-ethylene glycol)-poly(lactic acid)-poly-(β-amino ester) (PBAE) triblock copolymers to deliver docetaxel (DTX) and improve the anti-tumor activity of DTX. PBAE was synthesized by ring opening polymerization and Michael addition reaction, its structure and molecular weight was characterized by ¹H NMR, the dissociation constant of base (pK_b) were determined by acid-base titration method. The critical micelles concentration (CMC) of copolymers was measured by pyrene fluorescence spectroscopy. DTX loaded copolymer micelles were prepared by membrane hydration method. The size and its distribution as well as the stability of micelles were determined by laser light scattering analysis. The drug loading content (DL), entrapment efficiency (EE) and cumulative drug release from micelles were evaluated by high-performance liquid chromatography (HPLC). The sizes of DTX drug-loaded micelles were in the range of 10 to 100 nm with narrow distribution. DL of DTX in PBAE1 and PBAE2 micelles was (5.3 ± 0.10) % and (4.9 ± 0.05) %, respectively, with EE was (93.8 ± 1.70) % and (87.2 ± 4.10) %, respectively. The drug-loaded micelles showed pH sensitive drug release properties under weak acidic conditions, which showed potential drug release of DTX under mild acidic tumor environment. A mouse Lewis lung carcinoma model was established to evaluate the therapeutic efficacy of micellar DTX formulations. Significant inhibitory effect of the nanodrugs was observed with DTX dosages of 10 and 20 mg·kg^-1, respectively. Moreover, the pH responsive PBAE1-DTX micellar drug exhibited stronger therapeutic efficacy on mice xenograft tumor, as compared with the non pH sensitive micellar drug (PELA-DTX) and free DTX. All animal experiments were performed according to the animal ethical standards and approved by the Animal Experiments and Ethical Committee of China Academy of Chinese Medical Sciences (No. 2017090110). The in vivo anti-tumor activity studies showed that the tumor volume growth rates of mice in different drug-administered groups were: PBAE1-DTX 20 mg·kg^-1 < PBAE1-DTX 10 mg·kg^-1 < PELA-DTX 10 mg·kg^-1 < DTX 10 mg·kg^-1 < normal saline, with the PBAE1-DTX group as the most potent group for tumor inhibition. The current pH sensitive DTX nano-micelles showed high potential in further studies to promote the application of nano DTX formulations for tumor treatment.