Objective To investigate the expression of Toll-like receptor 4 (TLR4) of peripheral blood mononuclear cell (PBMC) in the different prognosis of patients with severe sepsis and its relation with endotoxin-tolerant.Methods Thirty-five patients with severe sepsis (severe sepsis group) and 15 healthy volunteers (control group),respectively stayed in ICU 24 h and physical examination in the day measured TLR4 expression of PBMC by flow cytometry and measured the serum of tumor necrosis factor (TNF)-α and interleukin (IL)-10 by enzyme-linked immunosorbentassay.Simultaneous separation of peripheral blood of PBMC,addition of 40 μ g/ml lipopolysaccharide (LPS) cultured for 24 h,and TLR4 expression of PBMC was measured in the same manner and the culture supernatant of TNF-α and IL-10.Results Thirty-five patients with severe sepsis survivor 25 cases (survivor group) and death 10 cases (death group),28 d death rate was 28.6％ (10/35).The TLR4 expression of PBMC in severe sepsis group was significantly lower than that in control group [(11.09 ± 8.90) MFI vs.(33.72 ± 12.59) MFI,P ＜ 0.01],the serum TNF-α and IL-10 in severe sepsis group were significantly higher than those in control group [(96.66 ± 45.33) ng/L vs.(2.53 ± 1.21) ng/L,(149.79 ± 67.15) ng/L vs.(34.56 ± 19.08) ng/L,P ＜ 0.01].There was no significant difference in TLR4 expression of PBMC between survivor group and death group (P ＞ 0.05).The TLR4 expression of PBMC in control group after LPS stimulation was significantly higher than that before LPS stimulation [(50.22 ± 19.23) MFI vs.(33.72 ± 12.59) MFI,P ＜ 0.05],survivor group and death group after LPS stimulation were significantly lower than those before LPS stimulation [(4.55 ± 2.30) MFI vs.(11.21 ±7.92) M FI and (5.46 ± 3.44) M FI vs.(10.15 ± 9.70) MFI,P ＜ 0.01].The culture supernatant of TNF-α,IL-10 in survivor group and death group were significantly lower than those in control group [(22.34 ± 8.27)and (19.49 ±5.35) ng/L vs.(88.70 ±34.21) ng/L,(54.29 ±32.89) and (98.04 ±40.26) ng/L vs.(146.56 ± 52.18) ng/L,P ＜ 0.01],but the culture supernatant of IL-10 in death group was significantly higher than that in survivor group (P ＜ 0.05).Conclusion Different prognosis of patients with severe sepsis have endotoxin tolerance and different inflammatory cytokine secretion abifity.

A questionnaire survey on learning motivation of standardized training and influence factors was carried out and 94 residents of general practice responded. The results indicated that over 80% respondents showed a positive attitude to study and hoped to obtain opportunity for continuing education;76% thought the training program was basically rational but still need to be improved; 94% felt that the training model should be adapted to the real conditions and work requirements of Chinese community health centers. The authors suggest some measures to improve the training including suitable textbooks, more rational training programs and further improvement of education system.

Aim To observe the effect of“Ying-nutrient and Wei-defense unblocking collaterals prescription”on the carotid sympathetic nerve in early atherosclero-sis. Methods The rabbits were randomly divided into 6 groups:Control group, high-fat group, Complex mod-el group, GSTL-H group, GSTL-L group and ATO group. The control group was fed with common food-stuffs, High-fat group with high-fat diet to build early atherosclerosis model, and all the other groups with high-fat diet combined with carotid artery cannula to build early atherosclerosis carotid artery injury rabbit model. All groups were given corresponding medicines intragastrically once a day for 4 weeks. The GSTL-H and GSTL-L group was given Guishaotongluo ultrafine powder 0. 6 g·kg-1·d-1, 0. 3 g·kg-1·d-1, and the ATO group was given suspension of atorvastain so-lution 2. 5 mg · kg-1 · d-1 . Biochemical method was used to detect blood lipid change. HE staining was ap-plied to observe the pathological morphology of intima-media, The content of NE in the carotid arterial was detected by ELISA. The immunohistochemical staining was used to detect the protein expression of NGF, TH around the carotid arterial. The expression of NGF, TH in the carotid artery adventitia was detected by Western blot. Results Compared with normal group, the levels of TC,TG and LDL-C in high-fat group and complex model group were significantly increased( P<0. 01). The degree of the intimal hyperplasia,the con-tent of NE and sympathetic density ( NGF, TH protein expression and distribution ) of the cartoid artery in complex model group were heavier compared with those in high-fat group; the lipid levels, degree of the inti-mal hyperplasia and sympathetic density ( NGF, TH protein expression and distribution ) in the GSTL-H, GSTL-L group were milder in varying degrees compa-ring with those in the complex model group(P<0. 05, P<0. 01 ) . Conclusion “Ying-nutrient and Wei-de-fense unblocking collaterals prescription” can reduce rabbit carotid atherosclerosis, and the mechanism may be related to regulating the sympathetic nerve of arterial wall.

Objective To systematically evaluate the efficacy and safety of immune checkpoint inhibitors in the treatment of advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC). Methods CNKI, Wanfang, PubMed, EMBASE, ClinicalTrials, Cochrane Library and other databases were searched to collect the clinical trials of immune checkpoint inhibitors in the treatment of advanced GC/GEJC. The retrieval time was from the inception to Nov. 2019. Outcome measures mainly included ORR, DCR, PFS, OS and toxicities. The adoption rate difference and hazard ratio were effect measures. Meta-analysis was performed using RevMan 5.3 software. Results We included seven literatures with a total of 1949 patients. Meta-analysis showed that for the patients with advanced GC/GEJC, the second-line or later immune checkpoint inhibitor therapy improved the overall survival rate at 12 and 18 months; the OS of the patients was prolonged, compared with chemotherapy/placebo therapy (all P < 0.05). The incidence of adverse reactions of any grade or ≥grade 3 caused by immune checkpoint inhibitor therapy was lower than that caused by chemotherapy/placebo. Conclusion Immune checkpoint inhibitor treatment could improve survival endpoints in some patients with advanced GC/GEJC, and the incidence of common adverse reactions is low.

Objective: To investigate the prospective effects of the consumption of protein and animal foods before menarche on the age at menarche among Chinese girls. Methods: This paper was based on the data collected in the China Health and Nutrition Survey(CHNS) from 1997 to 2015. A total of 683 girls aged 6 and over who had completed information on age at menarche, height, weight, per capita annual household income, maternal education level and participated in at least one complete dietary survey within 1 to 4 years before menarche were included. Urban-rural stratified multivariable linear regression model was used to examine the effects of protein and animal foods intake before menarche on Chinese girls age at menarche in urban and rural areas. Results: After adjusted for total energy intake, body mass index standard deviation score and per capita annual household income, the consumption of meat before menarche was negatively associated with the age at menarche among rural Chinese girls(B=-0.003, P=0.00), but not among urban Chinese girls(B=0.002, P>0.05). Total protein, dairy, eggs and aquatic products intake before menarche were not associated with Chinese girls age at menarche in urban and rural areas(B=0.002, -0.001, 0.003, 0.000; 0.001, 0.001, -0.001, -0.003, P>0.05). Conclusion Higher intake of meat before menarche might lead to earlier menarche onset in rural Chinese girls. The consumption of total protein, dairy, eggs, and aquatic products before menarche did not affect the age at menarche in Chinese girls.

Objectives: To evaluate the tumor-infiltrating PD-1 positive lymphocytes and regulatory T cells (Treg) as prognosis predic-tors of metastatic renal cell carcinoma (mRCC), and investigate the expression of PD-1 and Treg cells in mRCC and elucidate their corre-lation with clinicopathological parameters and prognosis. Methods: A total of 269 mRCC patients from June 2007 to June 2017 in Zhongshan Hospital, Fudan University, were included in the study. The expression of PD-1 and Tregs in mRCC samples were detected by immunohistochemistry. The relationship between the expression of PD-1 and Tregs was analyzed. Results: PD-1 positive expression in mRCC was 31.60% (85/269) and it was positively correlated with the tumor Fuhrman grade and negatively correlated with progno-sis. Tumor infiltration of Tregs in mRCC was 36.80% (99/269), and it was also positively correlated with the tumor Fuhrman grade and negatively correlated with prognosis. Univariate analysis showed that PD-1 positive lymphocytes and high Treg infiltration numbers were negatively correlated with overall survival (OS) and progression free survival (PFS) rates. Thus, PD-1 positive lymphocytes and high Treg infiltration numbers are independent prognostic indicators of OS and PFS and when combined, they can render a better pre-diction for prognosis. Conclusions: Intra-tumoral infiltration of PD-1 positive lymphocytes and Tregs can be used as significant prognos-tic indicators of mRCC, and the combined predictive effect is better than the individual predictive effect. Therefore, evaluating the number of PD-1 positive lymphocytes or infiltrating Tregs in mRCC is helpful in clinically estimating mRCC prognosis in patients.

Objective To evaluate the effect and mechanism of tribulus terrestris in kidney calcium oxalate stone in rats.Methods Sisty healthy male Wistar rats were divided into control group,model group,low-dose prevention group,high-dose prevention group,low-dose treatment group,high-dose treatment group by random number table method,each group of 10 rats.The control group was had free access to water,the model group was given 1％ ethylene glycol had free access to water,and the low-dose prevention group was given 1％ ethylene glycol had free access to water while was added in Tribulus terrestris extract 250 mg/(kg · d) treated by gavage,the high-dose prevention group was given 1％ ethylene glycol had free access to water while was added in Tribulus terrestris extract 500 mg/(kg · d) treated by gavage.The low-dose treatment group received 1％ ethylene glycol had free access to water while was added in tribulus terrestris extract 250 mg/(kg · d) treated by gavage on the 15th day.The high-dose treatment group received 1％ ethylene glycol had free access to water while was added in tribulus terrestris extract 500 mg/(kg · d) treated by gavage on the 15th day.At the end of the experiment on the 28th day,the body weight,blood urea nitrogen,creatinine,P,Ca2+,Mg2+ content,24 h urine volume,24 h urine Ca2+,Mg2 +,P,oxalic acid secretion,renal tissue homogenate detection of superoxide dismutase (SOD),glutathione peroxidase (GPX),malondialdehyde content of each group were detected.The crystal deposition and pathological changes of calcium oxalate were observed under the microscope.Measurement data were expressed as mean ± standard deviation (Mean ± SD),multiple comparisons between groups were performed using LSD-t test,and comparison between groups was performed by one-way anova analysis of variance.Results Compared with the control group,the rats in the model group had blood urea nitrogen (28.93 ±3.37) mmol/L,creatinine (162.31 ± 34.08) μmol/L,24 h uric acid (132.67 ± 27.96) μmol,Ca2+ (18.24 ± 1.94) μmol/24 h,the content of malondialdehyde (191.04 ± 20.56) nmol/mgprot in kidney homogenate was significantly increased,blood Ca2+ (2.01 ±0.28) mmol/L,renal GPX (479.82 ± 136.97) μmol/gprot,SOD(1.54 ±0.21) U/mgprot decreased significantly,these differences were statistically significant (P ＜ 0.05).Renal histopathology showed low-dose and high-dose prevention and treatment groups kidney calcium oxalate crystals and kidney damage were less than the model group.Conclusion The extract of Tribulus terrestris has a beneficial effect against calcium oxalate urinary stone formation induced by ethylene glycol.

Objective: To explore the differences in the gut microbiota of primary school students with different levels of sugar sweetened beverage intake, so as to provide scientific evidence for better identification of health risks in children and the development of targeted health policies. Methods: In June 2022, a total of 192 healthy primary school students from Chengdu were selected using a stratified cluster random sampling method. The sugar sweetened beverage intake was assessed through a dietary frequency questionnaire. Based on the median daily sugar sweetened beverage intake, primary school students were categorized into a low intake group ( n =96) and a high intake group ( n =96). The gut microbiota in fresh fecal samples from the two groups of primary school students was analyzed using 16S rRNA high throughput sequencing, and the diversity and community structure differences in the gut microbiota were compared. Results: Children in the low intake group had a sugar sweetened beverage intake of (21.3±1.6) mL/d, while the high intake group had an intake of (269.6±37.3) mL/d. Diversity analysis results showed that there were no statistically significant differences between the low intake and the high intake group in terms of α diversity metrics: Observed_otus index [298.50 (259.75, 342.25), 305.50 (244.25, 367.75)], Goods_coverage index [1.00 (1.00, 1.00), 1.00 (1.00, 1.00)], Chao index [304.18 (260.75, 348.78), 305.88 (245.68, 370.88)], Shannon index [5.88 (5.29, 6.45), 5.71 (4.89, 6.28)] and Simpson index [0.95 (0.91, 0.97), 0.94 (0.88, 0.97)] ( Z =-0.64, -0.76, -0.54, -1.76, -1.67, P >0.05). Furthermore, no statistically significant difference was observed in β diversity between the two groups ( R 2=0.006, P >0.05). At the genus level, the abundance of Blautia [0.033 (0.018, 0.055)] and Fusicatenibacter [0.009 (0.005, 0.015)] were higher in the low intake group compared to the high intake group [0.024 (0.013, 0.041),0.006 (0.003, 0.011)]and differences were statistically significant ( Z =-2.52, -2.81, P <0.05). LEfSe analysis highlighted intergroup differences primarily in Blautia, Fusicatenibacter and Sarcina( LDA= 3.56,3.12,3.53, P <0.05). Conclusions There is no significant difference in the diversity and overall structure of the gut microbiota in primary school students with different levels of sugar sweetened beverage intake. However, there are species variations at the genus level. The information can serve as a scientific basis for identifying health risks in primary school students and formulating targeted health strategies.

Objective To establish a HPLC fingerprints of Biyuanjing capsules. Methods The column was Agilent SB-C₁₈(4.6mm×250 mm, 5 µm). The mobile phase was acetonitrile-water with gradient elution at a flow rate of 1.0 ml/min. The detection wavelength was 210 nm. The detection time was 80 min. Results The HPLC fingerprints of Biyuanjing capsules were established. Twenty common peaks were confirmed, of which, 15 peaks were belonging to each crude drug and 5 peaks were identified as chemical components. The overall similarity of the fingerprints of 10 batches of samples was above 90% comparing with the control. Conclusion This method can be used for the quality control of Biyuanjing capsules.

Objective: To investigate the incidence and pathogen distribution of ventilator-associated pneumonia (VAP) among preterm infants admitted to level Ⅲ neonatal intensive care units (NICU) in China. Method: A prospective study was conducted in 25 level Ⅲ NICU, enrolling all preterm infants <34 weeks gestational age admitted to the participating NICU within the first 7 days of life from May 2015 to April 2016. Chi-square test, t test and Mann-Whitney U test were used for statistical analysis. Result: A total of 7 918 patients were enrolled, within whom 4 623(58.4%) were males. The birth weight was (1 639±415) g and the gestational age was (31.4±2.0) weeks; 4 654(58.8%) infants required non-invasive mechanical ventilation and 2 154(27.2%) required intubation. Of all the mechanically ventilated patients, VAP occurred in 95 patients. The overall VAP rate was 7.0 episodes per 1 000 ventilator days, varying from 0 to 34.4 episodes per 1 000 ventilator days in different centers. The incidence of VAP was 9.6 and 6.0 per 1 000 ventilator days in children′s hospitals and maternity-infant hospitals respectively, without significant differences (t=1.002, P=0.327). Gram-negative bacilli (76 strains, 91.6%) were the primary VAP microorganisms, mainly Acinetobacter baumannii (24 strains, 28.9%), Klebsiella pneumonia (23 strains, 27.7%), and Pseudomonas aeruginosa (10 strains, 12.0%). Conclusion The incidence of VAP in China is similar to that in developed counties, with substantial variability in different NICU settings. More efforts are needed to monitor and evaluate the preventable factors associated with VAP and conduct interventions that could effectively reduce the occurrence of VAP.