Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

ObjectiveBased on the ultrastructure of enteric nervous system （ENS）-platelet-derived growth factor receptor α positive （PDGFRα⁺） cell - smooth muscle cell （SMC） network， the effect and mechanism of Shuwei Decoction （舒胃汤） for rats with functional dyspepsia （FD） of liver-depression and spleen-deficiency syndrome were explored. MethodsFifty SD rats were divided into blank group， model group， low-， medium- and high-dose Shuwei Decoction groups randomly， with 10 rats in each group. The blank group was not set up， and the other 4 groups were set up with the modified composite cause （chronic restraint stress + tail irritation + excessive fatigue + diet disorder） for 21 days， resulting in FD model rats with liver-depression and spleen-deficiency syndrome. After successful modelling， rats in the low-， medium- and high-dose groups were given 3.78， 7.56 and 15.12 g/（kg·d） of Shuwei Decoction by gavage， respectively， while rats in the blank group and the model group were given 10 ml/（kg·d） of saline by gavage； all of them were given gavage once a day for 14 days. Body mass increase were collected before and after gavage， and compared after the experiment； the elevated cross maze experiment was conducted to observe the percentage of staying time and the percentage of times entering the open arm of rats； the gastric emptying rate and small intestinal propulsion rate were measured by black semi-solid paste； HE staining was used to observe histopathology of the gastric antrum； the Western Blotting and RT-qPCR were used to detect the expression levels of PDGFRα， small conductance calcium activated potassium （SK3）， and purinergic G protein-coupled receptor P2Y1 （P2Y1 R）， and mRNA expression in gastric antrum； immunofluorescence double staining was used to detect the co-localization of PDGFRα with receptor tyrosine kinase （C-kit）， protein gene product 9.5 （PGP9.5）， Sk3， and smooth muscle cells （SMCs） in gastric sinusoidal tissues； and transmission electron microscopy was used to observe the ultrastructure of the ENS-PDGFRα⁺ cell-SMC network. ResultsHE staining results showed that the mucosal folds of gastric tissue were clear in all groups， no organic lesions such as bleeding， ulceration and swelling were observed， and the arrangement of gastric glands in the lamina propria of gastric sinusoidal tissues in model group and low-dose Shuwei Decoction group was disordered. The arrangement of gastric glands in lamina propria in medium- and high-dose Shuwei Decoction groups was more orderly， and the lesion degree was less than that in model group and low-dose Shuwei Decoction group. Compared with the blank group， the growth value of body mass， the percentage of open arm retention time， the percentage of times entering the open arm， the small intestine propulsion rate， and the gastric empty rate of rats in the model group significantly decreased after gavage； the expressions of PDGFRα， Sk3， P2Y1 protein and mRNA in gastric sinusoidal tissues decreased； the co-localization expression of PDGFRα with C-kit， Sk3， SMC and PGP9.5 significantly decreased （P＜0.05 or P＜0.01）； the ultrastructure of ENS-PDGFRα⁺ cell-SMC network was damaged without gap junction. Compared with model group and low-dose Shuwei Decoction group， the growth value of body mass， the percentage of open arm retention time， the percentage of times entering the open arm， the small intestine propulsion rate， and the gastric empting rate of rats in medium- and high-dose Shuwei Decoction groups increased after gavage； the expressions of PDGFRα， Sk3， P2Y1 protein and mRNA in gastric sinusoidal tissues increased； the co-localization expression of PDGFRα with C-kit， Sk3， SMC and PGP9.5 significantly increased （P＜0.05 or P＜0.01）； the ultrastructure of ENS-PDGFRα⁺ cell-SMC network was intact. Compared with medium-dose Shuwei Decoction group， the protein expressions of PDGFRα， Sk3 and P2Y1， the mRNA expressions of PDGFRα and Sk3， and the co-localization expressions of PDGFRα and C-kit， Sk3， SMC， and PGP9.5 in high-dose Shuwei Decoction group increased （P＜0.05 or P＜0.01）. ConclusionShuwei Decoction can improve the pathological lesion of the gastric antrum in the FD model rats with liver-depression and spleen-deficiency syndrome and increase the gastric emptying rate as well as the small intestinal propusion rate. The mechanism of Shuwei Decoction on FD rats with liver-depression and spleen-deficiency syndrome is related to the protection of the ultrastructural integrity of ENS-PDGFRα⁺ cell-SMC network.

Prostate cancer （PCa） is one of the most common malignant tumors in the male genitourinary system. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a carcinogenic pathway responsible for the migration， proliferation， and drug resistance of various cancers. In recent years， as the research on the pathogenesis of PCa is deepening， the role of the PI3K/Akt signaling pathway in the development of PCa has attracted much attention. Traditional Chinese medicine， comprehensively regulating multiple components， targets， and pathways， has shown great potential in the treatment of PCa. This article reviews the research progress of traditional Chinese medicine targeting the PI3K/Akt signaling pathway in the treatment of PCa and discusses the expression of the PI3K/Akt signaling pathway in PCa， which involves inhibiting apoptosis of PCa cells， promoting the cell cycle， invasion， and migration of PCa cells， promoting tumor tissue angiogenesis， and mediating the androgen receptor. Additionally， it summarizes the single Chinese medicines that target and regulate this pathway， including Hedyotis diffusa， Taxus chinensis， Bovisc Alculus， and Atractylodis Macrocephalae Rhizoma. The active ingredients of these Chinese medicines mainly include flavonoids， alkaloids， terpenes， polyphenols， lignans， and other compounds. The Chinese medicine compound prescriptions targeting the PI3K/Akt pathway mainly include Wenshen Sanjie prescription， Jianspi Lishi Huayu prescription， Yishen Tonglongtang， Qilan prescription， Xihuangwan， and modified Shenqi Dihuangtang. This review is expected to provide a scientific basis for deeply understanding the pathogenesis of PCa and identifying potential therapeutic targets， as well as to provide new ideas for clinical research and drug development for PCa.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To investigate the feasibility of mimics software in analyzing a new type of complex anterior cervical fixation—anterior transpedicular screw fixation+zero notch internal fixation.Methods From January 2021 to September 2022,50 normal pedestrians who underwent cervical spine CT scanning were selected for C1-C7 segment scanning,including 27 males and 23 females,aged from 25 to 65 years old with an average of(46.0±9.0)years old.The dicom format is exported and engraved into the CD,and use the mimics software to perform 3D reconstruction of each segment.A simulated screw is placed on the image according to the critical value of zero notch screw(head and tail angle 44°,internal angle 29°).The posi-tion of zero notch screw in each segment is observed to determine the feasibility of anterior transpedicular screw fixation plus zero notch internal fixation.Results For the upper zero notch screws the three-dimensional images of the cervical spine across all 50 subjects within the C3-C7 segments demonstrated safe position,wwith no instances of intersection with ATPS.For the lower zero notch screw,in C3-C4 and C4-C5,4 out of 50 subjects are in the safe position in the three-dimensional images of cervical ver-tebrae,and 46 cases could achieve secure screw placement when the maximum caudal angle is(32.3±1.9)° and(36.1±2.2)°,respectively.In C5-C6 and C6-C7 segments,no lower zero notch screws intersected with ATPS,and all screws are in safe posi-tions.Conclusion Lower cervical anterior pedicle screw fixation plus zero notch internal fixation can achieve successful nail placement through the selected entry point and position.

Pituitary thyroid-stimulating hormone(TSH)adenomas is a rare pituitary disorder,accounting for less than 2%of pituitary adenomas.The clinical manifestations primarily include mild to moderate symptoms of hyperthyroidism,corresponding symptoms caused by other anterior pituitary hormone secretion disorders,and symptoms resulting from the mass effect of pituitary tumors.Pituitary TSH adenomas need to be differentiated from primary hyperthyroidism(Graves'disease)and resistance to thyroid hormone(RTH),as misdiagnosis can lead to tumor growth and aggravation of the condition.Currently,with the help of sensitive laboratory tests,imaging examinations,and targeted functional tests,pituitary TSH adenomas can be diagnosed relatively accurately.The preferred treatment is surgical resection.In cases where surgery is not feasible or unsuccessful,radiotherapy or medical therapy can be considered.Long-acting somatostatin analogs can effectively reduce tumor volume and decrease TSH secretion,thereby normalizing free 3,5,3',5'-tetraiodothyronine(FT4)and free 3,5,3'-triiodothyronine(FT3).Early identification and effective treatment are significant for patients with pituitary TSH adenomas.This review summarizes the epidemiology,pathological characteristics,screening objects,clinical manifestations,auxiliary examinations,diagnosis and treatment,follow-up and evaluation of pituitary TSH adenoma,aiming to provide guidance for the clinical diagnosis and treatment of this condition.

Objective To develop a prediction tool for post-endoscopic retrograde cholangiopancreatography(ER-CP)early biliary tract infection(PEEBI)in patients with choledocholithiasis,and assist clinical decision-making be-fore ERCP and early personalized intervention after ERCP.Methods An observational bidirectional cohort study was adopted to select inpatients with choledocholithiasis who underwent ERCP in a hospital.Directed acyclic graph(DAGs)and the least absolute shrinkage and selection operator(LASSO)were used to predict PEEBI based on lo-gistic regression,and the models were compared and validated internally and externally.Results From January 1,2020 to September 30,2023,a total of 2 121 patients with choledocholithiasis underwent ERCP were enrolled,of whom 77(3.6％)developed PEEBI,mostly in the first 2 days after surgery(66.2％).The major influencing fac-tors for PEEBI were non-iatrogenic patient-related factors,namely diabetes mellitus(OR=2.43,95％CI:1.14-4.85),bile duct malignancy(OR=3.95,95％CI:1.74-8.31)and duodenal papillary diverticulum(OR=4.39,95％CI:1.86-9.52).Compared with the LASSO model,the DAGs model showed higher ability(3.0％)in com-prehensive discrimination(P=0.007),as well as good differentiation performance(D=0.133,P=0.894)and cal-ibration performance(x2=5.499,P=0.703)in external validation.Conclusion The DAGs model constructed in this study has good predictive performance.With the help of this tool,targeted early preventive measures in clinical practice can be taken to reduce the occurrence of PEEBI.

Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Objectives:To analyze the impact of the kyphotic apical vertebra(KAV)position on sagittal plane characteristics and quality of life in patients with degenerative kyphosis(DK).Methods:A retrospective analy-sis was conducted on the clinical and imaging data of 68 DK patients hospitalized and treated in the Depart-ment of Orthopedic Surgery,Nanjing Drum Tower Hospital from February 2010 to December 2022.There were 8 males and 60 females,aged 46-76 years old(60.6±6.5 years).The patients were divided into two groups based on the position of the KAV:Group 1(G1)included 38 patients with the KAV at or above L1,and Group 2(G2)included 30 patients with the KAV below L1.The thoracic kyphosis(TK),lumbar lordosis(LL),sagittal vertical axis(SVA),pelvic incidence(PI),pelvic tilt(PT),sacral slope(SS),T1-pelvic angle(TPA),and global kyphosis(GK)were measured on standing full-spine lateral X-rays before operation,and the value of PI-LL was calculated.Health related quality of life(HRQoL)was assessed using the Scoliosis Research So-ciety-22(SRS-22)questionnaire,Oswestry disability index(ODI),visual analog scale(VAS)score,and SF-36 questionnaire.Independent samples t-tests were used to compare sagittal plane parameters and HRQoL scores between the two groups.Pearson correlation analysis was employed to examine the relationship between sagit-tal plane parameters and HRQoL scores.Results:There was no significant difference in the age and sex ra-tios between the two groups(P＞0.05).The GK,LL,TK,SVA,PI,PT,SS,TPA,and PI-LL in G1 group were respectively 61.3°±20.0°,26.9°±18.9°,32.3°±19.0°,53.5±48.1mm,40.4°±13.4°,24.8°±12.6°,17.0°±11.7°,23.0°±13.5°,and 21.6°±15.6°,which in G2 group were 38.8°±16.0°,14.4°±13.7,10.8±9.8°,96.5±67.8mm,44.8°±16.2°,30.1°±10.8°,14.7°±11.5°,32.6°±14.5°,and 33.8°±18.3°.The GK,LL,and TK were significantly greater in G1 group than those in G2 group(P＜0.05),and SVA,TPA,and PI-LL were less in G1 group than those in G2 group(P＜0.05).The VAS score,ODI,SF-36 physical component score(PCS),SF-36 mental com-ponent score(MCS),SRS-22(function,pain,self-image,mental health,subtotal score)in G1 group were 4.2±1.6,(37.9±15.2)％,45.8±11.3,48.6±12.7,and(17.6±4.6,18.6±4.3,17.7±4.5,17.8±4.9,71.7±9.3),which were 5.8±1.7,(48.6±20.0)％,38.2±12.9,44.2±13.1,and(15.6±4.5,16.0±3.6,16.6±4.9,17.1±4.3,65.4±11.1)in G2 group.G1 group was lower in VAS score and ODI significantly(P＜0.05)and higher in SRS-22 subtotal score,SRS-22 pain domain score,and SF-36 PCS significantly(P＜0.05)than G2 group.Pearson correlation analysis showed that SVA was positively correlated with VAS and ODI in both groups(G1 group:r=0.437,P=0.006 and r=0.356,P=0.028;G2 group:r=0.405,P=0.027 and r=0.408,P=0.025),while negatively correlated with SF-36 PCS(G1 group:r=-0.365,P=0.024;G2 group:r=-0.410,P=0.024).TPA was positively correlated with VAS score in both groups(G1 group:r=0.343,P=0.035;G2 group:r=0.369,P=0.045).In G2 group,SVA neg-atively correlated with SRS-22 subtotal score(r=-0.391,P=0.033),and PI-LL was positively correlated with VAS score(r=0.390,P=0.033).Conclusions:The position of KAV affects the pelvic-spinal sagittal alignment obviously in DK patients,and the patients with KAV located below L1 level have significantly higher SVA,TPA,and PI-LL compared to the patients whose KAV located at or above L1 level,which is significantly associated with decreased quality of life.