Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To investigate the effect of paeoniflorin on aerobic glycolysis of macrophages induced by resiquimod.Methods THP-1 cells were treated with phorbol ester(PM A)to differentiate into macrophages.The cells were divided into control group,model group and low,medium,high dose experimental group.The cells in the control group were cultured normally;in the model group,2 μg·mL-1 resiquimod was used to stimulate macrophages for 24 h to induce aerobic glycolysis.The low,medium and high dose experimental groups were treated with 1,10 and 100 μmol·L-1 paeoniflorin for 24 h on the basis of the model group.Cell activity was detected by cell counting kit-8(CCK-8)method.Lactate and glucose determination kit were used to detect lactate secretion and glucose consumption of cells in each group.The protein and mRNA expression levels of(PKM2)and(LDHA)were detected by Western blot and real-time fluorescence quantitative polynucleotide chain reaction(q-PCR)respectively.Immunofluorescence method was used to compare the fluorescence intensity of PKM2 in each group.Results After 24 h stimulation of THP-1 cells with 2 μg·mL-1 resiquimod,the glucose contents in cell culture supernatants of control group,model group and low,medium and high dose experimental groups were(14.70±0.44),(9.83±0.43),(10.68±0.29),(11.79±0.33)and(13.63±0.74)mmol·L-1;the lactate secreted by cells were(6.17±0.48),(11.94±0.55),(9.08±0.55),(7.79±0.66)and(6.50±0.55)mmol·L-1;the protein expression levels of PKM2 in cells were 1.00±0.00,1.33±0.18,1.02±0.17,0.74±0.17 and 0.73±0.18;the protein expression levels of LDHA were 1.00±0.00,1.20±0.09,0.90±0.14,0.76±0.12 and 0.78±0.17;the PKM2 mRNA levels were 1.00±0.09,2.11±0.23,1.98±0.31,1.38±0.25 and 0.93±0.32;the LDHA mRNA levels were 1.00±0.13,1.85±0.25,1.44±0.21,0.91±0.24 and 0.96±0.14;the average fluorescence intensities of PKM2 were 136.41±33.63,217.94±5.33,210.27±1.03,204.14±3.27 and 186.79±14.03.Compared with control group,the above indicators in model group showed statistically significant differences(P＜0.05,P＜0.01);compared with model group,the differences in the above indicators in medium and high dose experimental group were all statistically significant(P＜0.05,P＜0.01).Conclusion Paeoniflorin can inhibit the aerobic glycolysis of macrophages induced by resiquimod.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Epilepsy is a chronic disease characterized by recurrent,sudden,and excessive synchronous discharge of neurons in the brain,leading to transient brain dysfunction,and inflammatory responses in specific regions within the central nervous system are common features of epilepsy.In recent years,there has been increasing evidence that endoplasmic reticulum stress is involved in the pathology of epilepsy,which activates the unfolded protein response,then regulate and control nuclear factor kappa-B(NF-κB),efficiently induces glial cell activation through the release of pro-inflammatory signals,in turn affects epileptogenesis and seizures by triggering neuroinflammation.This review focuses on the close link between endoplasmic reticulum stress and glial cell activation-mediated neuroinflammation in epilepsy pathology,aiming to provide insights for a deeper understanding of epilepsy.

Objective To construct HEK 293T cells that express tardigrade Dsup protein fused with green fluorescent protein copGFP in order to study the effect of Dsup protein on proliferation of HEK 293T cells.Methods The CRISPR/Cas9 gene knock-in system was constructed.The target gene fragments of Dsup,copGFP,EF1α and puromycin were amplified by PCR and inserted into pAAVS1-SFFV to construct the fusion vector of Dsup and copGFP,which was known as pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro.pAAVS1-SFFV-Dsup-copGFP-EF1 α-Puro and pAAVS1-CRISPR-Cas9 vector were co-transfected into HEK 293T cells before Dsup gene was inserted into the AAVS1 region of HEK 293T cells via homologous recombination.The HEK 293T cells expressing Dsup gene were obtained following puromycin selection,flow cytometry sorting and genome identification.The expression of Dsup at mRNA and protein levels and proliferation-related genes(MCM2,MCM4,PCNA,Ki-67)were examined to investigate the effects of Dsup gene on the proliferation of HEK 293T-Dsup-copGFP cells.Results The pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro recombinant vector was constructed,and the HEK 293T-Dsup-copGFP cells with Dsup gene inserted in the AAVS1 region were obtained,where both Dsup mRNA and protein were expressed.The cell proliferation rate of HEK 293T-Dsup-copGFP was higher than that of HEK 293T-Control-copGFP(P＜0.001).Further investigation revealed that the expressions of Ki-67 and MCM4 protein in HEK 293T-Dsup-copGFP were significantly higher than in the control group,indicating that the knock in of Dsup gene might enhance the proliferation ability of human cells by promoting the expression of Ki-67 and MCM4 protein.Conclusion A gene editing vector is constructed,and stable cell line HEK 293T-Dsup-copGFP for Dsup fusion expression with copGFP is established.The expression of Dsup gene in HEK 293T cells can promote cell proliferation,possibly by upregulating the expressions of Ki-67 and MCM4 protein.

Objective To explore the safety and effectiveness of the robot-assisted system for transforaminal percutaneous endoscopic in the treatment of lumbar disc herniation with lumbar instability.Methods From October 2021 to March 2023,26 patients with single-segment lumbar disc herniation and lumbar spinal instability were treated with robot-assisted system for transforaminal percutaneous endoscopic.The operation time,intraoperative blood loss,incision length,postoperative drainage volume,postoperative ambulation activity time,postoperative hospitalization time were record.The intervertebral space height and the lumbar lordosis angle before and after surgery were observed and compared.Pain level was evaluated using the visual analogue scale(VAS).The clinical efficacy was evaluated by Oswestry disability index(ODI).The interbody fusion was evalu-ated by Brantigan Steffee criteria.Results All patients successfully completed the operation,the operation time ranged form 105 to 109 min with an average of(150.8±24.1)min.Intraoperative blood loss ranged form 35 to 88 ml with an average of(55.5±16.4)ml.Incision length ranged form 1.4 to 3.5 cm with an average of(2.3±0.8)cm.Postoperative drainage volume ranged form 15 to 40 ml with an average of(28.5±7.8)ml.Postoperative ambulation time ranged form 15 to 30 h with an aver-age of(22.8±4.5)h.Postoperative hospitalization time was 3 to 7 d with an average of(4.2±1.3)d.Total of 26 patients were followed up,the duration ranged from 12 to 16 months with an average of(14.0±1.3)months.The VAS and ODI at 1 week[(2.96±0.72)points,(41.63±4.79)％]and 12 months[(1.27±0.60)points,(13.11±2.45)％]were significantly different from those before surgery[(6.69±0.93)points,(59.12±5.92)％],P＜0.0 1.The height of the intervertebral space(11.95±1.47)mm and lumbar lordosis(57.46±7.59)° at 12 months were significantly different from those before surgery[(6.67±1.20)mm,(44.08±7.79)°],P＜0.01.At 12 months after surgery,all patients had no pedicle screw rupture or dislocation of the fusion cage,and the intervertebral fusion was successful.According to Brantigan-Steffee classification,17 cases were grade D and 9 cases were grade E.Conclusion Robot-assisted system for transforaminal percutaneous endoscopic for the treatment of single-segment lumbar disc herniation with lumbar instability improved the accuracy and safety of the operation,and the clinical effect of early follow-up is accurate.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To assess the value eosin-nigrosine(E-N)staining and hypo-osmotic swelling test(HOST)in the diag-nosis of necrospermia and investigate the correlation of the degree of sperm necrosis with sperm DNA fragmentation index(DFI)and high DNA stainability(HDS).Methods:Using computer-assisted sperm analysis(CASA),we examined the sperm motility of 7 333 males seeking medical care in Maternal and Child Health Hospital of Hunan Province from May 2023 to July 2024,detected the sperm viability of those with asthenozoospermia by E-N staining and HOST,and measured the sperm DFI and HDS of those with necro-spermia by sperm chromatin structure assay(SCSA).Based on sperm progressive motility(PR％),we divided the asthenozoospermia patients into three groups(PR％20％-＜30％,PR％10％-＜20％and PR％＜10％),assessed the value of E-N staining and HOST in the diagnosis of necrospermia,and analyzed the correlation of the severity of sperm necrosis with sperm DFI and HDS.Results:Asthenozoospermia was diagnosed in 1 374(18.74％)of the 7 333 males.The incidence rates of necrospermia revealed by E-N staining in the mild,moderate and severe asthenozoospermia groups were 0.55％(5/913),3.80％(12/316)and 35.86％(52/145),respectively,with a total incidence of 0.94％(69/7333),while those detected by HOST were 0.99％(9/913),6.96％(22/316)and 46.21％(67/145),respectively,with a total incidence of 1.34％(98/7333).There were no statistically significant differences in the results of diagnosis between the two methods(x2=0.97,P＞0.05).Both E-N staining and HOST showed that sperm DFI in the necrospermia males was negatively correlated with sperm viability(r=-0.366,r=-0.333,P＜0.05),and so was sperm HDS,though with no statistically significant difference(P＞0.05).Conclusion:For males with PR％＜30％,sperm viability test should be conducted,with E-N staining as the choice of priority for the diagnosis of necrospermia.Sperm necrosis and sperm nuclear chromatin damage may be interactive risk factors.

Objective: To understand the current situation of vaccination services for adults in China, explore how to establish a stable and efficient vaccination service system for adults, and provide reference for formulating corresponding policies. Methods: The vaccination information systems of nine provinces in China were used to obtain information on urban and rural vaccination of influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPV23), and human papillomavirus vaccine (HPV) from 2019 to 2021. The indicator, vaccination rate/full vaccination rate, was used for statistical description. Results: The vaccination rate/full vaccination rate of the three vaccines in eastern China was generally higher than that in central and western China. The vaccination rate/full vaccination rate in urban areas was generally higher than that in rural areas. From 2019 to 2021, the vaccination rates of influenza vaccine among people aged 60 years and above in urban and rural areas were 2.96%, 6.29%, 6.14% and 1.29%, 2.58%, 2.94%, respectively. The vaccination rates of the PPV23 among people aged 60 years and above in urban and rural areas increased year by year, with rates of 0.38%, 1.05%, 1.15% and 0.14%, 0.49%, 0.59%, respectively. From 2019 to 2021, the HPV coverage of female adults aged 27-45 years in urban and rural areas increased year by year, with rates of 0.46%, 0.93%, 1.88% and 0.17%, 0.40%, 1.08%, respectively. Conclusion: The vaccination rates of influenza vaccine,PPV23 vaccine and HPV vaccine for adults in China are relatively low, with higher rates in the eastern region than in the central and western regions, and higher rates in urban areas than in rural areas. It is recommended to formulate corresponding health and economic policies and explore a suitable vaccination service system for adults in China to improve vaccination rates.
Adult ; Female ; Humans ; Influenza Vaccines/therapeutic use* ; Papillomavirus Infections ; Vaccination ; China ; Papillomavirus Vaccines/therapeutic use*