Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.

Objective To compare the clinical efficacy of natural orifice specimen extraction surgery(NOSES)combined with enhanced recovery after surgery(ERAS)and conventional laparoscopic surgery in treatment of rectal cancer patients.Methods A hundred patients with rectal cancer in the Department of Colorectal and Anal Surgery,the 940th Hospital of Joint Logistics Support Force of PLA were selected as the research objects from January 2019 to December 2021,including 49 cases treated with NOSES combined with ERAS were set as the observation group,and 51 cases treated with conventional laparoscopic surgery of rectal cancer were set as the control group.Postoperative C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),white blood cell count(WBC),percentage of neutrophil(NEUT),K+ concentration,postoperative peristalsis recovery time,first time out-of-bed activity,first liquid feeding time,removal time of urinary,and drainage tubes,hospital stay and intraoperative blood loss,number of lymph node detection,positive margin rate,incidence of complications,and pain score were compared between the two groups.Results The observation group showed significant lower postoperative CRP,PCT,IL-6 levels when compared with control group(P<0.05),while no significant difference in K+ concentration between the two groups(P>0.05).The recovery time of intestinal peristalsis,the time of the first out-of-bed activity,the first liquid feeding time,the time of removal of the urinary tube and the drainage tube,and the number of days of hospitalization in observation group were all superior to the control group(P<0.05).The observation group with the duration of surgery was longer than the control group,and the difference was statistically significant(P<0.05).There were no significant differences in intraoperative bleeding,number of lymph nodes detected and positive rate of resection margins between the two groups(P>0.05).There was no significant difference in the incidence of complications between the two groups(4.1%vs.7.8%,P>0.05).The observation group showed significant lower pain scores than control group on the 1st,2nd and 3rd day after surgery(P<0.05).Conclusions NOSES combined with ERAS in treatment of rectal cancer patients is safe and feasible,can narrow the surgical incision,alleviate stress response and postoperative pain,improve postoperative efficacy and reduce the occurrence of complications,so is worthy of promotion and application.

Objective To prepare a verteporfin-loaded poly(lactic-co-glycolic acid)nanoparticle(PLGA-VP NPs)and to verify its inhibitory effect on hepatocellular carcinoma cell line Hepa 1-6 and its in vivo safety.Methods PLGA-VP NPs were prepared by emulsion evaporation method,and the particle size and potential of PLGA-VP NPs were detected by dynamic light scattering(DLS).Mouse hepatocellular carcinoma cell line Hepa 1-6 was cultured in vitro and divided into control group(without any treatment),PLGA NPs group(adding PLGA NPs)and PLGA-VP NPs group(adding PLGA-VP NPs).The cell proliferation was detected by the Alamar Blue;the uptake of PLGA-VP NPs and apoptosis rate of cells were detected by flow cytometry;the expression levels of programmed death-ligand 1(PD-L1)protein,B-cell lymphoma-2(Bcl-2)protein and Bcl-2 associated X protein(Bax)were detected by Western blotting.C57 mice were divided into control group(phosphate buffered saline 100 μL)and PLGA-VP NPs group(tail vein injection of 2 μg·μL-1 PLGA-VP NPs 100 μL).The main organs of mice were observed by hematoxylin-eosin(HE)staining.Results The particle size of PLGA-VP NPs was about(124.00±1.80)nm,and the potential was about(-38.00±1.40)mV.When the concentrations of PLGA-VP NPs were 0,0.5,1,2,2.5,3,4,5 mg·mL-1,the cell survival rates were(100.00±2.02)％,(87.33±3.74)％,(55.86±9.71)％,(30.32±6.30)％,(26.03±2.60)％,(23.81±2.09)％,(23.63±1.29)％and(19.75±3.32)％;the half maximal inhibitory concentration of PLGA-VP NPs on Hepa 1-6 was 0.87 mg·mL-1.The uptake rates of Hepa 1-6 to PLGA-VP NPs at 0,2,4,8,12 and 24 h were 0,(3.27±0.10)％,(7.32±1.36)％,(27.03±1.11)％,(44.97±1.43)％and(68.37±0.94)％,respectively.The apoptosis rates of the control group,the PLGA NPs group and the PLGA-VP NPs group were(9.26±1.42)％,(11.08±1.16)％and(27.27±1.12)％;the relative expression levels of PD-L1 protein were 1.00±0.01,1.00±0.08 and 0.21±0.06;the relative expression levels of Bcl-2 protein were 1.20±0.02,0.43±0.01 and 0.54±0.07;the relative expression levels of Bax protein were 0.35±0.02,1.09±0.07 and 1.30±0.06,respectively.The above indexes show statistically significant differences in between the PLGA-VP NPs group and the control group,PLGA NPs group(all P＜0.05).After HE staining,comparing to the normal group,there was no obvious abnormality in the main organs of the mice in the PLGA-VP NPs group.Conclusions PLGA-VP NPs were successfully synthesized,and the nanoparticles have inhibitory effects on Hepa 1-6 hepatocellular carcinoma cells,can reduce the expression of PD-L1 protein,and have good in vivo safety.

To treat age-related macular degeneration(AMD),verteporfin has been widely used for more than 20 years in ophthalmology as a photodynamic agent.In recent years,researchers have found that,in addition to the therapeutic effect of verteporfin on age-related macular degeneration,it also has great potential in the treatment of tumors.The killing effect of verteporfin on tumors has been studied and reported in a large number of studies.It can not only kill tumor cells under visible light as a photodynamic agent,but also kill tumor cells directly under non-photoactivated conditions.This article mainly reviews the current research status of verteporfin's role in cancer treatment.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective To investigate the protective effect of placental mesenchymal stem cells(P-MSCs)on pancreatic trauma(PT)in rats.Methods Sixty healthy adult male SD rats were randomly divided into control group,pancreatic trauma group(inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area),and P-MSCs group[inject 1 ml of P-MSCs(1×106/ml)locally in the pancreatic injury area and around the trauma area],with 20 rats in each group.The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa.Five rats were sacrificed at 1,3,5,and 7 d after modeling in each group,and serum and pancreatic tissue were collected.HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed.The ELISA method was used to measure the concentrations of serum amylase(AMS),lipase(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,and transforming growth factor-β1(TGF-β1),as well as the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)in pancreatic tissue.The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.Results Compared with control group,pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma,including the generation of peritoneal fluid increased(P<0.05),the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased(P<0.05),and serum levels of AMS,LPS,TNF-α,IL-6,and MPO activity increased early and showed a decreasing trend over time(P<0.05),while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time(P<0.01),level of TGF-β1 in the early decline showed an upward trend over time(P<0.01),and the apoptosis index(AI)significantly increased(P<0.001).Compared with pancreatic trauma group,P-MSCs group showed an improvement in the overall morphology of pancreatic tissue,the generation of peritoneal fluid decreased(P<0.001),the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased(P<0.05),and serum levels of AMS,LPS,IL-6,TNF-α and MPO activity returned to normal levels faster(P<0.05);and the rate of anti-inflammatory factors IL-10,TGF-β1 and SOD activity elevation increased(P<0.05),the AI increased(P<0.001).Conclusion P-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair,reducing local and systemic inflammation,improving tissue oxidative stress,and enhancing pancreatic acinar cell apoptosis.

Objective To investigate the correlation between the expression of Toll-like receptor 4(TLR4)and chitosanase 3-like protein 1(CHI3L1)in colon cancer tissue and the prognosis of patients after radical surgery.Methods A total of 152 patients who underwent radical colon cancer surgery in our hospital from January 2017 to May 2018 were collected and divided into the good prognosis group(n=97)and the poor prognosis group(n=47)according to the 5-year survival status after surgery.Immunohistochemical staining was applied to detect the expression levels of TLR4 and CHI3L1 in colon cancer tissues and adjacent tissues;the correlation between the expression of TLR4 and CHI3L1 in colon cancer tissue and the prognosis of patients was analyzed,and the influencing factors for prognosis of colon cancer patients were analyzed.Results The positive expression rates of TLR4 and CHI3L1 in colon cancer tissues were obviously higher than those in adjacent tissues(P<0.05).The expression of TLR4 in colon cancer tissue was related to the degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05),the expression of CHI3L1 was related to the tumor diameter,degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05).Compared with the good prognosis group,the poor prognosis group had higher proportions of patients with poorly differentiated tumor,clinical stageⅢ,lymph node metastasis,and positive expression of TLR4 and CHI3L1(P<0.05).The 5-year survival rate of patient with TLR4 positive expression was 60.38%,which was lower than that of 86.84% of patients with TLR4 negative expression(χ2=9.104,P<0.05);the 5-year survival rate of patients with CHI3L1 positive expression was 58.06%,which was lower than that of 84.31% of patients with CHI3L1 negative expression(χ2=10.935,P<0.05).The positive expression of TLR4 and CHI3L1,poorly differentiated tumor,clinical stage Ⅲ,and lymph node metastasis were the independent risk factors for the prognosis of colon cancer patients(P<0.05).Conclusion TLR4 and CHI3L1 are related to the occurrence and clinicopathological features of colon cancer,and the positive expression of TLR4 and CHI3L1 in colon cancer tissues is not conducive to the prognosis of patients,so both of them are expected to become clinical treatment targets.

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.