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 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 compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.
Anastomotic Leak/etiology* ; Humans ; Laparoscopy/methods* ; Postoperative Complications/epidemiology* ; Prognosis ; Prospective Studies ; Rectal Neoplasms/pathology* ; Rectum/surgery* ; Retrospective Studies ; Transanal Endoscopic Surgery/methods* ; Treatment Outcome

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.
Amino Acid Sequence ; Cloning, Molecular ; Geranyltranstransferase/genetics* ; Pogostemon ; Transcription Factors/genetics*

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective: To explore the incidence and risk factors of postoperative surgical site infection (SSI) after colon cancer surgery. Methods: A retrospective case-control study was performed. Patients diagnosed with colon cancer who underwent radical surgery between January 2016 and May 2021 were included, and demographic characteristics, comorbidities, laboratory tests, surgical data and postoperative complications were extracted from the specialized prospective database at Department of General Surgery, Peking Union Medical College Hospital. Case exclusion criteria: (1) simultaneously multiple primary colon cancer; (2) segmental resection, subtotal colectomy, or total colectomy; (3) patients undergoing colostomy/ileostomy during the operation or in the state of colostomy/ileostomy before the operation; (4) patients receiving natural orifice specimen extraction surgery or transvaginal colon surgery; (5) patients with the history of colectomy; (6) emergency operation due to intestinal obstruction, perforation and acute bleeding; (7) intestinal diversion operation; (8) benign lesions confirmed by postoperative pathology; (9) patients not following the colorectal clinical pathway of our department for intestinal preparation and antibiotic application. Univariate analysis and multivariate analysis were used to determine the risk factors of SSI after colon cancer surgery. Results: A total of 1291 patients were enrolled in the study. 94.3% (1217/1291) of cases received laparoscopic surgery. The incidence of overall SSI was 5.3% (69/1291). According to tumor location, the incidence of SSI in the right colon, transverse colon, left colon and sigmoid colon was 8.6% (40/465), 5.2% (11/213), 7.1% (7/98) and 2.1% (11/515) respectively. According to resection range, the incidence of SSI after right hemicolectomy, transverse colectomy, left hemicolectomy and sigmoid colectomy was 8.2% (48/588), 4.5% (2/44), 4.8% (8 /167) and 2.2% (11/492) respectively. Univariate analysis showed that preoperative BUN≥7.14 mmol/L, tumor site, resection range, intestinal anastomotic approach, postoperative diarrhea, anastomotic leakage, postoperative pneumonia, and anastomotic technique were related to SSI (all P<0.05). Multivariate analysis revealed that anastomotic leakage (OR=22.074, 95%CI: 6.172-78.953, P<0.001), pneumonia (OR=4.100, 95%CI: 1.546-10.869, P=0.005), intracorporeal anastomosis (OR=5.288, 95%CI: 2.919-9.577,P<0.001) were independent risk factors of SSI. Subgroup analysis showed that in right hemicolectomy, the incidence of SSI in intracorporeal anastomosis was 19.8% (32/162), which was significantly higher than that in extracorporeal anastomosis (3.8%, 16/426, χ(2)=40.064, P<0.001). In transverse colectomy [5.0% (2/40) vs. 0, χ(2)=0.210, P=1.000], left hemicolectomy [5.4% (8/148) vs. 0, χ(2)=1.079, P=0.599] and sigmoid colectomy [2.1% (10/482) vs. 10.0% (1/10), χ(2)=2.815, P=0.204], no significant differences of SSI incidence were found between intracorporeal anastomosis and extracorporeal anastomosis (all P>0.05). Conclusions: The incidence of SSI increases with the resection range from sigmoid colectomy to right hemicolectomy. Intracorporeal anastomosis and postoperative anastomotic leakage are independent risk factors of SSI. Attentions should be paid to the possibility of postoperative pneumonia and actively effective treatment measures should be carried out.
Case-Control Studies ; Colonic Neoplasms/surgery* ; Humans ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection/etiology*

Objective:To provide a scientific basis for the standardized operation of clinical disinfection by comparing and analyzing the influence of disinfection times on the accuracy of digital intraoral scanning.Methods:The author prepared 10 brand-new intraoral scanning heads (Trios, 3Shape, Denmark), scan the same plaster standard dentition model after 1, 20, 40, and 60 times of pressure steam sterilization, and obtained the data of four groups of experimental groups A, B, C, D, and scan the model 5 times repeatedly after each disinfection cycle of each scanning head. A model scanner (D2000, 3Shape, Denmark) was used to scan the standard dentition model, and the scan results were used as the control group data. Vernier calipers and measurement software were used to measure the arch length (the distance between the mesial cheek tips of the first molars on both sides of the maxillary) and the front and back length (the distance from the tongue protrusion of the right incisor to the buccal tip of the first molar on the right of the upper jaw) of the plaster model and the data of the 4 experimental groups. The line distance results of the 4 groups of experimental groups were compared for statistical analysis, and the trueness and precision values of the 4 groups of experimental groups were compared for statistical analysis.Results:The length of the arch across the 4 experimental groups increased with the increase in the number of disinfection ( P<0.05), and there were statistical differences compared with the measurement results of the plaster model ( P<0.05); the differences in the length of the dental arch were not statistically significant ( P>0.05). The treness of the 4 experimental groups is statistically significant ( P<0.05), and the trueness was from high to low in order of group A [(114.85±3.75) μm], group B [(124.65±3.85) μm], group C [(131.45±3.04) μm] and group D [(144.64±3.34) μm]; the precision of the 4 experimental groups was not statistically significant ( P>0.05). Conclusions:The number of times of pressure steam sterilization can affect the accuracy of the scanning results of the digital intraoral scanner, and with the increase of the number of sterilizations, the error of the scanning results also tends to increase. The number of sterilizations has no effect on the repeatability of the digital scanning results. The increase in the number of times of pressure steam sterilization affects the accross of the arch but has no effect on the length of the dental arch, and the range of change of the length of the arch is within the clinically acceptable range. After 60 times of pressure steam sterilization, the accuracy of digital scan data can still meet clinical needs.

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.
Abdomen ; surgery ; China ; Drainage ; methods ; Evidence-Based Medicine ; Humans ; Practice Guidelines as Topic ; Societies, Medical ; organization & administration ; Surgical Wound Infection ; prevention & control ; Traumatology ; organization & administration ; Vacuum

Objective: To evaluate the safety, efficacy and tolerability of China-made sildenafil citrate (Jinge) in the treatment of ED. METHODS: We conducted a multi-center, randomized, double-blind and placebo-controlled clinical trial among 222 ED patients in five urological or andrological clinics of China. The patients were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n = 111) for 8 weeks. We obtained and analyzed the demographic and clinical characteristics of the patients, the scores of International Index of Erectile Function (IIEF), the success rate of sexual intercourse, and the incidence of adverse events. RESULTS: No statistically significant differences were found between the patients of the SC and those of the placebo group in the mean age (［47.2±11.32］ yr vs ［46.67±13.08］ yr, P>0.05), psychological etiology (27.93% vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of smoking, drinking or allergy. Compared with the placebo controls, the SC-treated patients showed significant increases in the excellence rate of effectiveness (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%, P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The effectiveness rates on organic, psychogenic and mixed types ED were remarkably higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were observed in 32 cases in the SC group as compared with 13 in the placebo control. CONCLUSIONS China-made sildenafil citrate is an effective, safe and well-tolerated drug for ED of different etiologies in the Chinese population.
Aged ; China ; Coitus ; Double-Blind Method ; Drug Compounding ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Smoking ; Treatment Outcome