Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ). METHODS: A child with OFDSⅠ who received treatment at the Women and Children's Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children's Hospital (Ethic No.: EC 2024-063). RESULTS: The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c.710dup (p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child's parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS4_Moderate+PM2-Supporting+PM6_Supporting+PP4). CONCLUSION Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c.710dup (p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
Humans ; Female ; Orofaciodigital Syndromes/genetics* ; Exome Sequencing ; Retrospective Studies ; Mutation ; Child ; Proteins

OBJECTIVE: To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL). METHODS: A child who was admitted to Ningbo Women and Children's Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063). RESULTS: Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. CONCLUSION For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.
Child, Preschool ; Humans ; DNA Copy Number Variations/genetics* ; Down Syndrome/genetics* ; GATA1 Transcription Factor/genetics* ; Leukemia/congenital* ; Mosaicism ; Mutation ; Retrospective Studies ; Whole Genome Sequencing

ObjectiveTo investigate the mechanism of astragaloside-Ⅳ （AS-Ⅳ） in regulating pyroptosis to alleviate intestinal ischemia-reperfusion injury （IRI） by combining network pharmacology and in vivo experiments. MethodFirstly， the corresponding target genes of AS-Ⅳ were obtained from TraditionalChineseMedicineSystemsPharmacology（TCMSP） database and Swiss Target Prediction database， and the target genes related to intestinal IRI and Pyroptosis were obtained from GeneCards database， and the common target genes of the three were obtained by drawing Venn diagrams through unspiralized website. Protein-protein interaction （PPI） network was constructed by STRING database and Cytoscape software to screen common target genes and imported into Cytoscape software to obtain core target genes. Microbiotics platform was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis and prediction of the mechanism of action of AS-Ⅳ in regulating Pyroptosis to alleviate intestinal IRI. Then C57/BL6J mice were randomly divided into 5 groups normal group， model group（IR）， drug administration group （IR+AS-Ⅳ）， nucleotide-binding oligomerization structural domain-like receptor protein 3 （NLRP3） agonist NSS group （IR+AS-Ⅳ+NSS）， and NLRP3 inhibitor MCC950 group （IR+AS-Ⅳ+MCC950） by using a randomized numerical table method. The intestinal IRI model was established by clamping the superior mesenteric artery for 45 min and resuming perfusion for 2 h in the model group， the drug administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group， and the normal group was only separated from the vessels without clamping. The administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group were gavaged with astragaloside dissolved in 0.1% dimethylsulfoxide （50 mg·kg^-1） for 3 consecutive days before modeling， with the last gavage 2 h before modeling， and the remaining two groups were gavaged with equal amounts of saline. The NLRP3 agonist NSS group was injected intraperitoneally with 4 mg·kg^-1 of NSS 1 h before modeling， and the NLRP3 inhibitor MCC950 group was injected intraperitoneally with 10 mg·kg^-1 of MCC950 1 h before modeling.The mice were put to death by reperfusion for 2 h， and intestinal tissues were obtained. The levels of IL-18 and IL-1β were detected by enzyme linked immunosorbent assay（ELISA）， and the protein expression of thioredoxin-binding protein （TXNIP）， NLRP3， Caspase-1 and pyrocatechin D （GSDMD） were detected by Western blot， and the pathological changes of intestinal tissues were evaluated by Chiu's score. ResultNetwork pharmacological analysis showed that there were 1599 targets of intestinal IRI， 199 targets of AS-Ⅳ action， 197 targets of pyroptosis， and 20 targets common to all three. There were 10 core targets， including NLRP3， TXNIP， silencing information regulator 1 （SIRT1）， high mobility group protein 1 （HMGB1）， interleukin-18 （IL-18）， GSDMD， and metallo matrix protease-9 （MMP-9），et al. The results of in vivo experiments showed that compared with the normal group， Chiu's score was elevated in the model group， the levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of TXNIP， NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the model group，Chiu's score was decreased in the administered group and NLRP3 inhibitor MCC950 group，the level of IL-18，IL-1β inflammatory factors in the intestinal tissue of mice was decreased（P<0.05）， and the level of TXNIP，NLRP3，Caspase-1，GSDMD protein expression was decreased（P<0.05）. Compared with the administered group， Chiu's score was elevated in the NLRP3 agonist NSS group， the levels of IL-18， IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the NLRP3 inhibitor MCC950 group， the NLRP3 agonist NSS group had elevated Chiu's scores， elevated levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues （P<0.05）， and elevated levels of TXNIP，NLRP3， Caspase-1， and GSDMD protein expression （P<0.05）. ConclusionNetwork pharmacological predictions were consistent with the results of in vivo experiments， and astragaloside attenuated intestinal ischemia-reperfusion injury by inhibiting cellular pyroptosis through the TXNIP-NLRP3 signaling pathway.

Objective:To develop, validate and initially apply a joint function and health assessment scale for juvenile idiopathic arthritis patients.Methods:The first draft of the juvenile idiopathic arthritis joint function and health assessment scale was developed through literature analysis, discussion by the research team, semi-structured interviews, Delphi expert correspondence. From March to June 2024, a total of 260 children with juvenile idiopathic arthritis or their parents were prospectively recruited from Department of Rheumatology and Immunology, Children′s Hospital of Chongqing Medical University by convenience sampling method for pre-investigation and formal investigation.The reliability and validity of the scale were tested by item analysis, reliability analysis, exploratory factor analysis, content validity and criterion validity analysis, and the responsiveness of the scale to clinical changes was evaluated by estimating the minimum clinically important difference, and finally the formal scale was formed.Results:The juvenile idiopathic arthritis joint function and health assessment scale included disease activity assessment, daily activity and function assessment, pain, fatigue and disease outcome assessment, with a total of 5 dimensions and 24 items, in which the functional assessment subscale included 4 secondary dimensions and 18 items. The Cronbach′s α coefficient of the function assessment subscale was 0.88, the fold-half reliability was 0.86, and the test-retest reliability after 2-4 weeks was 0.84; the item-level content validity index was 0.80-1.00, and the scale-level content validity index was 0.93. Exploratory factor analysis extracted 4 common factors with a cumulative variance contribution of 70.0%. Preliminary application indicated the functional assessment subscale was moderately correlated with childhood health assessment questionnaire ( r=0.70, P<0.05), the total scale was strongly correlated with juvenile arthritis disease activity score-27 ( r=0.92, P<0.05), and moderately correlated with both active and limited joint count ( r=0.77, 0.68, both P<0.05). Reactivity analysis suggested that the minimum clinically important difference between the two visits of 41 children with clinical improvement and 25 children with disease activity was 0.49 (0.44, 0.54) and 0.51 (0.43, 0.58). Conclusion:The juvenile idiopathic arthritis joint function and health assessment scale has good reliability and validity, and has certain responsiveness to clinical changes, is simple and operable, and can be used as a tool for assessing joint function in children with juvenile idiopathic arthritis.

Objective To compare the efficacy and safety of three kinds of endoscopic minimally invasive treatment of internal hemorrhoids.Methods The clinical data of 222 patients with internal hemorrhoids who underwent endoscopic treatment in Shangyu People's Hospital of Shaoxing from January 2020 to June 2023 were retrospectively analyzed.According to the treatment method,the patients were divided into simple sclerotherapy group(40 cases),simple ligation group(114 cases)and combined group(68 cases).The perioperative indexes,postoperative adverse events,effective rate and satisfaction of three groups were compared.Results There was significant difference in operation time among three groups(P＜0.05),and the operation time of simple ligation group was the shortest.There was no significant difference in postoperative hospital stay among three groups(P＞0.05).The incidences of anal distention,postoperative pain and dysuria in simple ligation group and combined group were significantly higher than those in simple sclerotherapy group(P＜0.05).The incidence of postoperative bleeding in simple ligation group was significantly higher than that in simple sclerotherapy group and combined group(P＜0.05).There was significant difference in treatment effectiveness among three groups(P＜0.05),and combined treatment had the best effect.The satisfaction of three groups was higher,and the difference was not statistically significant(P＞0.05).Conclusion The three endoscopic minimally invasive treatment methods for internal hemorrhoids are safe and effective.Ligation combined with sclerotherapy can effectively improve symptoms,and the postoperative delayed bleeding are low,which is a safe and efficient treatment method.

Objective To investigate the anesthetic effects and adverse effects of cypropofol and propofol combined with alfentanil,respectively,for gastroenteroscopy.Methods A total of 162 patients who underwent elective gastroenteroscopy at the Gastrointestinal Endoscopy Center of the First Hospital of Lanzhou University from January to February 2024 were enrolled,including 86 males and 76 females,at an age of 18～65 years old,with a BMI value of 18～30 kg/m2,and ASA grade ≤ Ⅱ.They were randomly divided into propofol group(Group P)and cypropofol group(Group C),with 81 cases in each group.All patients were sedated with 0.7 μg/kg alfentanil,and in 30 s later,2 mg/kg propofol and 0.4 mg/kg cypropofol was intravenously dripped into Group P and Group C,respectively.When the modified alertness/sedation score(MOAA/S)≤1,a gastroscope was started to insert.The related indicators,including total procedure time,successful cases of sedation,induction time and awakening time,heart rate,blood pressure,and pulse oximetry saturation were recorded,occurrence of adverse reactions such as hypotension,respiratory depression,injection pain,intraoperative body movement,nausea and vomiting were observed,and the satisfaction of endoscopists and of patients to anesthesia were recorded and compared between the 2 groups.Results There were no statistical differences in the success rate of sedation,induction time and awakening time between the 2 groups.The patients of the Group C had more stable intraoperative vital signs,statistically lower incidences of injection pain,respiratory depression and hypotension(P＜0.05),and increased satisfaction for anesthesia(P＜0.05)when compared with those in Group P.No obvious difference were observed in the satisfaction of endoscopist to anesthesia between the 2 groups.Conclusion In combination with small-dose alfentanil,0.4 mg/kg cypropofol shows similar sedation effect as 2 mg/kg propofol in gastroenteroscopy,with comparable induction and awakening time.Cypropofol has more advantages in stable intraoperative vital signs,less adverse effects such as low blood pressure,respiratory depression and injection pain,higher the patient satisfaction,which is worthy of clinical promotion.

Objective:To explore the development and interaction between chronotype and depressive symp-toms among middle school students in Chongqing.Methods:A total of 1208 middle school students(613 in grade 7,595 in grade 10)were surveyed for three follow-ups at 6-month intervals.Periods T1-T3 represented baseline,6 months later,and 12 months later,respectively.Chronotype and depressive symptoms were measured by the Morn-ing and Evening Questionnaire-5(MEQ-5)and the Patient Health Questionnaire-9(PHQ-9).Analyses were per-formed using SPSS 26.0 and Mplus 8.3.Results:The MEQ-5 scores were lower in T1 than in T3,and the scores were lower in T2 than in T1 and T3(F=20.08,P＜0.001),suggesting a fluctuating trend of chronotype shifting to the Evening-type first after baseline and then to the Morning-type.The PHQ-9 scores exhibited a significant differ-ence among the three-time measurements(x2/df=9.77/2,P＜0.01).But pairwise comparisons did not yield any statistically significant findings(P＞0.05).The cross-lagged panel model showed that pathways of Ti MEQ-5 scores negatively predicted Ti+1 PHQ-9 scores(βTi-Ti+1=-0.12/-0.09,P＜0.05)and TiPHQ-9 scores nega-tively predicted Ti+1 MEQ-5 scores(βTi-Ti+1=-0.07/-0.11,P＜0.05).Conclusion:Chronotype and depressive symptoms show some changes in adolescents.The more inclined adolescents are to the Evening-type,the higher the likelihood of depressive symptoms occurring later.The more severe the depressive symptoms,the greater the likeli-hood of a subsequent shift to the Evening-type.

Objective:To investigate the effect of using two different input functions to reconstruct 18F-FDG PET/CT Patlak multi-parameter images on the quantitative parameters of lung cancer lesions. Methods:The original whole-body dynamic 18F-FDG PET/CT scan data of lung cancer patients in the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University were retrospectively analyzed. The total scan time was 75 min. Two input functions were used for Patlak multi-parameter reconstruction: ① Image-derived input function(IDIF)using the Time-activity curve(TAC)of descending aorta from 0 min to 75 min. ② Population-based input function (PBIF) developed by Yale University. Metabolic rate of FDG (MR FDG) and Distribution volume (DV) images were obtained by Patlak multi-parameter analysis software using the above input functions. The region of interest (ROI) method was used to delineate the lesions to obtain multi-parameter quantitative information, including the max, peak and mean value of MR FDG and DV. Paired t-test was used for statistical analysis. Results:The original data of 27 lung cancer patients who received whole-body dynamic 18F-FDG PET/CT imaging were reconstructed by Patlak with two different input functions. The max, peak and mean values of MR FDG-IDIF and MR FDG-PBIF in lung cancer lesions were as follows: (0.26 ± 0.15), (0.19 ± 0.12), (0.14 ± 0.08)μmol·min -1·ml -1 and (0.26 ± 0.15), ( 0.20 ± 0.13), (0.15 ± 0.09)μmol·min -1·ml -1, with no statistically significant difference between two functions( P > 0.05). The max, peak and mean values of DV IDIF and DV PBIF were (165.56 ± 99.89)%, (117.66 ± 72.24)%, (62.16 ± 33.65)% and(170.04 ± 103.93)%, (121.91 ± 73.71)%, (65.05 ± 37.17)%, with no statistically significant difference between two functions ( P > 0.05). Conclusions:The population-based input function may be an alternative for patients who could not lie supine for long time during whole-body dynamic 18F-FDG PET/CT Patlak multi-parameter imaging.