This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis （CIP） based on the theory of "cough attributed to the five zang （脏） organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs"， drug toxicity triggers cancer toxin， leading to disharmony among the five zang organs， and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore， treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice， CIP can be classified into four syndrome patterns， including lung yin depletion， deficiency of both the lung and the spleen with phlegm-dampness， liver fire harassing the lung， and lung-kidney yin deficiency. Correspondingly， Chaimai Jinluo Runfei Decoction （柴麦金络润肺汤） is used to nourish yin and moisten the lung； Qigui Peitu Huayin Decoction （芪桂培土化饮汤） is used to fortify the spleen and tonify the lung， resolve dampness and dispel phlegm； Chaidan Shuyu Runjin Decoction （柴丹疏郁润金汤） is used to drain liver and clear the lung； and Dimai Jinshui Xiangsheng Decoction （地脉金水相生汤） is used to nourish the kidney and moisten the lung.

Objective To compare the different intervention effect of aerobic exercise or complex poly-saccharide supplement on gut microbiota(GM),GM-related metabolic pathway genes,as well as fat and weight losing of obese rats induced by high-fat diet. Methods Thirty-two male Sprague-Dawley rats were randomly divided into a control group,an obesity control(OC) group,an aerobic exercise (AE) group and a complex polysaccharide intervention(CPI) group,each of 8. The AE group was giv-en moderate intensity treadmill aerobic training for 6 weeks,while the CPI group underwent plant poly-saccharide gavage for the same period of time. Morphological indicators were measured and recorded,serum regulators of lipid metabolism were collected,and feces were collected for metagenomic sequenc-ing and analysis. Results(1) Before the intervention,the body weight of group OC was significantly higher than the control group(P<0.01). However,after 6-week aerobic exercise,the body weight and Lee's index of group OC reduced significantly(P<0.05). (2) The concentrations of peroxisome prolifera-tor-activated receptor γ(PPAR-γ) and leptin(LEP) in serum of the OC group were significantly high-er than the control group(P<0.001),but that of lipoprotein lipase(LPL) was significantly lower than the control group(P<0.001). The serum concentrations of PPAR-γ in group AE were significantly low-er than group OC(P<0.01),while those of PPAR-γ and LEP in group CPI were significantly lower than group OC(P<0.001). (3) The abundance of Akkermansia mucinphila,Alistipes finegoldii,Bacteroides ovatus and Gram-negative bacterium cL10-2b-4 in group OC was significantly lower than the control group(P<0.05),with that of Prevotella copri in group AE significantly higher than group OC and that of Helicobacter rodentium significantly lower than the latter(P<0.05). Moreover,the abundance of Bifido-bacterium animalis in group CPI was significantly higher than group OC,while that of Alistipes shahii was significantly lower than the latter(P<0.05). (4) Compared with the control group,the obese group was significantly enriched in Vibrio cholerae pathogenic cycle,Staphylococcus aureus infection and vari-ous types of N-glycan biosynthesis related genes. Moreover,the abundance of salmonella infection and N-glycan biosynthesis-related genes in group AE was significantly lower than group OC(P<0.05),and that of Vibrio cholerae disease-cycle related genes in group CPI was significantly lower than group OC (P<0.05). Conclusion The imbalance in the gut microbiota structure,and the abnormal expression of related metabolic pathway genes both play important roles in the phenotype changes of high-fat diet in-duced rats,which can be effectively relieved by aerobic exercise and complex polysaccharide gavage. However,there are obvious differences in the effects and possible mechanisms between the above two intervention methods.

Objective To compare the different intervention effect of aerobic exercise or complex poly-saccharide supplement on gut microbiota(GM),GM-related metabolic pathway genes,as well as fat and weight losing of obese rats induced by high-fat diet. Methods Thirty-two male Sprague-Dawley rats were randomly divided into a control group,an obesity control(OC) group,an aerobic exercise (AE) group and a complex polysaccharide intervention(CPI) group,each of 8. The AE group was giv-en moderate intensity treadmill aerobic training for 6 weeks,while the CPI group underwent plant poly-saccharide gavage for the same period of time. Morphological indicators were measured and recorded,serum regulators of lipid metabolism were collected,and feces were collected for metagenomic sequenc-ing and analysis. Results(1) Before the intervention,the body weight of group OC was significantly higher than the control group(P<0.01). However,after 6-week aerobic exercise,the body weight and Lee's index of group OC reduced significantly(P<0.05). (2) The concentrations of peroxisome prolifera-tor-activated receptor γ(PPAR-γ) and leptin(LEP) in serum of the OC group were significantly high-er than the control group(P<0.001),but that of lipoprotein lipase(LPL) was significantly lower than the control group(P<0.001). The serum concentrations of PPAR-γ in group AE were significantly low-er than group OC(P<0.01),while those of PPAR-γ and LEP in group CPI were significantly lower than group OC(P<0.001). (3) The abundance of Akkermansia mucinphila,Alistipes finegoldii,Bacteroides ovatus and Gram-negative bacterium cL10-2b-4 in group OC was significantly lower than the control group(P<0.05),with that of Prevotella copri in group AE significantly higher than group OC and that of Helicobacter rodentium significantly lower than the latter(P<0.05). Moreover,the abundance of Bifido-bacterium animalis in group CPI was significantly higher than group OC,while that of Alistipes shahii was significantly lower than the latter(P<0.05). (4) Compared with the control group,the obese group was significantly enriched in Vibrio cholerae pathogenic cycle,Staphylococcus aureus infection and vari-ous types of N-glycan biosynthesis related genes. Moreover,the abundance of salmonella infection and N-glycan biosynthesis-related genes in group AE was significantly lower than group OC(P<0.05),and that of Vibrio cholerae disease-cycle related genes in group CPI was significantly lower than group OC (P<0.05). Conclusion The imbalance in the gut microbiota structure,and the abnormal expression of related metabolic pathway genes both play important roles in the phenotype changes of high-fat diet in-duced rats,which can be effectively relieved by aerobic exercise and complex polysaccharide gavage. However,there are obvious differences in the effects and possible mechanisms between the above two intervention methods.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

Objective:To explore the association between nighttime sleep duration and semen quality.Methods:By using a cross-sectional study, 3357 men were investigated by questionnaire for nighttime sleep duration, the time of falling asleep and falling asleep duration in the Reproductive Center of Shenzhen People's Hospital from August 2017 to August 2018. Semen quality parameters were obtained by computer-aided semen analysis system (CASA). Multiple linear regression was used to analyze the relationship between nighttime sleep duration and semen quality parameters. According to age and body mass index (BMI) stratification, the relationship between nighttime sleep duration and semen quality parameters was further discussed.Results:Compared with males with nighttime sleep duration between 6-8 h, the sperm progressive motility and total motility were 49.15% and 59.49%, respectively, which were significantly lower in the males with nighttime sleep duration≥8 h after adjusting for age, BMI, abstinence time, exercise, drinking and smoking, with regression coefficients, β=-3.16, 95% confidence interval ( CI)=-5.77--0.55 and β=-3.22, 95% CI=-5.93--0.51, respectively. Compared with the shortest duration of falling asleep group (<10 min), the increase of falling asleep duration was related to the decrease of sperm progressive motility ( P=0.045). The total sperm motility of falling asleep duration between 31-60 min group was also significantly lower than that of the shortest falling asleep duration group （ β=-3.80, 95% CI=-6.54--1.06, P=0.007）. Further stratification analysis showed that among the subjects aged 35 to 39 years, the sperm progressive motility of men with nighttime sleep duration less than 6 h was lower than that of 6-8 h group ( β=-4.01, 95% CI=-7.84-0.18, P=0.04). And among the subjects aged more than 40 years, the total sperm number of the men who slept ≥8 h at night was lower than that of the men with nighttime sleep duration between 6-8 h （percentage changes: -47.84%, 95% CI=-72.29%--2.19%, P=0.04）. The progressive and total sperm motility of men with BMI≥24 kg/m 2 and nighttime sleep duration ≥8 h were lower than those with BMI≥24 kg/m 2 in 6-8 h nighttime sleep duration group, and the corresponding regression coefficients were β=-5.75, 95% CI=-10.40--1.10, P=0.02 and β=-6.85, 95% CI=-11.69--2.00, P=0.01. Conclusion:In men ≥40 years old or BMI≥24 kg/m 2, the nighttime sleep duration ≥8 h were associated with the decreased sperm progressive motility and total motility.

Objective:To explore the association between nighttime sleep duration and semen quality.Methods:By using a cross-sectional study, 3357 men were investigated by questionnaire for nighttime sleep duration, the time of falling asleep and falling asleep duration in the Reproductive Center of Shenzhen People's Hospital from August 2017 to August 2018. Semen quality parameters were obtained by computer-aided semen analysis system (CASA). Multiple linear regression was used to analyze the relationship between nighttime sleep duration and semen quality parameters. According to age and body mass index (BMI) stratification, the relationship between nighttime sleep duration and semen quality parameters was further discussed.Results:Compared with males with nighttime sleep duration between 6-8 h, the sperm progressive motility and total motility were 49.15% and 59.49%, respectively, which were significantly lower in the males with nighttime sleep duration≥8 h after adjusting for age, BMI, abstinence time, exercise, drinking and smoking, with regression coefficients, β=-3.16, 95% confidence interval ( CI)=-5.77--0.55 and β=-3.22, 95% CI=-5.93--0.51, respectively. Compared with the shortest duration of falling asleep group (<10 min), the increase of falling asleep duration was related to the decrease of sperm progressive motility ( P=0.045). The total sperm motility of falling asleep duration between 31-60 min group was also significantly lower than that of the shortest falling asleep duration group （ β=-3.80, 95% CI=-6.54--1.06, P=0.007）. Further stratification analysis showed that among the subjects aged 35 to 39 years, the sperm progressive motility of men with nighttime sleep duration less than 6 h was lower than that of 6-8 h group ( β=-4.01, 95% CI=-7.84-0.18, P=0.04). And among the subjects aged more than 40 years, the total sperm number of the men who slept ≥8 h at night was lower than that of the men with nighttime sleep duration between 6-8 h （percentage changes: -47.84%, 95% CI=-72.29%--2.19%, P=0.04）. The progressive and total sperm motility of men with BMI≥24 kg/m 2 and nighttime sleep duration ≥8 h were lower than those with BMI≥24 kg/m 2 in 6-8 h nighttime sleep duration group, and the corresponding regression coefficients were β=-5.75, 95% CI=-10.40--1.10, P=0.02 and β=-6.85, 95% CI=-11.69--2.00, P=0.01. Conclusion:In men ≥40 years old or BMI≥24 kg/m 2, the nighttime sleep duration ≥8 h were associated with the decreased sperm progressive motility and total motility.

Objective:To examine the roles of follicular helper T(Tfh)cells,serum IL-21 and B cells in the pathogenesis of alcohol abuse non-traumatic osteonecrosis of the femoral head ( NONFH ) .Flow cytometry was used to measure the frequencies of peripheral blood inducible Tfh cells and B cells in alcohol abuse NONFH patients and healthy controls.The disease progression and the extent of femoral head collapse,the serum IL-21 were quantified.Methods: A significantly higher percentages of CD19+B cells(t=3.765,P=0.0005),CD86+CD19+B cells(t=5.506,P<0.0001),and CD95+CD19+B cells(t=4.152,P=0.0002) in patients than those in controls was found.The percentages of CD86+CD19+B cells were positively associated with the index of femoral head collapse in alcohol abuse NONFH(P<0.0001,r=0.536).Results: The frequencies of Tfh cells (t=7.611,P<0.0001),and IL-21+Tfh cells (t=5.281,P<0.0001) were higher than those in controls;The frequencies of Tfh cells were positively associated with the percentages of CD19+B cells(P=0.0002,r=0.455),IL-21+Tfh cells were positively associated with the percentages of CD86+CD19+B cells(P=0.0002,r=0.447).Conclusion: Tfh cells and B cells may participate in the pathogenesis of alcohol abuse NONFH,and increased CD86+CD19+B cells may be associated with the extent of femoral head collapse,the interaction of Tfh cells and B cells may have an im-portant role in pathogenesis of alcohol abuse NONFH.

Objective To investigate antimicrobial resistance among gram-negative bacilli in China in 2010.Methods A total of 1 259 consecutive and non-repetitive gram-negative bacilli were isolated from 13 teaching hospitals from September to December in 2010 in China.All of these isolates were sent to the central laboratory for re-identification and susceptibility testing.The MIC of meropenem and other antibacterial agents were determined by agar dilution method.Interpretive results was determined by CLSI M100-S21.Results The activity of 14 antibacterial agents against 845 Enterobacteriaceae isolates was as follows in order:meropenem ( 98.1％,829 ),amikacin ( 94.0％,794 ),imipeuem ( 90.0％,761 ),piperacillin/tazobactam ( 87.5％,739 ),cefepime ( 83.0％,701 ),ertapenem ( 82.4％,696 ),cefoperazone/sulbactam ( 80.3％,678 ),colistin (75.4％,637),ceftazidime (70.0％,591 ),ciprofloxacin (59.1％,499 ),cefoxitin ( 54.8％,463 ),ceftriaxone ( 53.5％,452 ),cefotaxime ( 52.3％,442 ) and minocycline(51.5％,435).The prevalence of ESBL was 61.3％ (106/173) in Escherichia coli,which was much higher than 41.2％ (70/170) in Klebsiella pneumoniae.The susceptibility rate of Klebsiella pneumoniae against meropenem,imipenem,amikacin and colistin were more than 90％,but were highly resistant to ceftriaxone and cefotaxime.Over 80％ of Enterobacter cloacae,Enterobacter aerogenes,Citrobacter freundii,were susceptible to meropenem,amikacin,cefepine,cefoperazone/sulbactam,imipenem,piperacillin/ tazobactam,and ertapenem.The most active antibiotics against Pseudomonas aeruginosa were Colistin (98.4％,182),Amikacin ( 85.9％,159 ),Piperacillin/Tazobactam ( 80％,148 ),Ceftazidime ( 79.5％,147),Meropenem (74.1％,137),Ciprofloxacin (74.1％,137),Cefepime (73.5％,136),Imipenem (71.9％,132) and Cefoperazone/Sulbactam (70.8％,131 ).Less than 37％ of Acinetobacter baumannii isolates were resistant to carbapenems.The susceptible rate to Minocycline was 47.8％.Colistin kept good activity against Acinetobacter baumannii (susceptible rate,97.8％,n =176),The prevalence of Pan-drug resistant P.aeruginosa and A.baumannii was 18.9％ (n =35),and 61.8％ (n =108),respectively.Conclusions Carbapenems remained very high activity against Enterobacteriaceae.Increasing resistance to the antimicrobials agents test among A.baumanni and P.aeruginosa,especially carbapenems among A.baumanni brought great concern.

Objective To probe the changes of plasma albumin concentration and its correlation with that of blood inflammatory factors at the postoperative early stage in patients undergoing intraabdominal surgery. Methods From August 2008 to March 2009, 45 patients undergoing abdominal surgery were divided into three groups according to different types of operation with 15 cases in each group, cholecystectomy group( A), chole cystectomy plus common bile duct exploration group(B) and radical resection of alimentary duct maliguance group (C). Before the surgery and 12,24,48,72 h after operation, plasma albumin contentserum IL-6 and TNF-α concentration were measured. Results Postoperatively the content of plasma albumin did not change significantly in group A ( P ＞ 0.05 ), while that decreased after operation in group B and group C(P ＜0.01 ). The postoperative concentration of serum IL-6 and TNF-α increased in group A at 12, 24 h and 48 h after operation(P ＜0.01 ). In group B and group C IL-6 and TNF-α increased at all tested time point after operation ( P ＜ 0.01 ). The postoperative alterations of IL-6 and TNF-α were statistically different between the three groups at all time points(P ＜0.01 ). The content of plasma albumin was in a negative correlation with the concentration of IL-6 and TNF-α; ( r = - 0.376, P = 0.000; r =-0.772,P = 0.000). Conclusions The content of plasma albumin decreased at the early stage after major and moderate abdominal surgery. The content of plasma albumin was in a negative correlation with the concentration of inflammatory factors at the early stage after abdominal surgery.

Objective: To investigate the effects of trentment with hydroxythy starch(130/0.4) on the serum albumin and immunologic function in postoperative patients with obstructive jaundice.Methods: 24 patients with obstructive jaundice were randomly divided into the control group(n=12) and hydroxythy starch(130/0.4) (HS) group(n=12). The serum ALB was detected 1d, 3d, 5d, 7d after the operation,and the immunologic index were detected 1d and 7d after the operation.Results: The ALB content of control group and HS group were not significantly different in the postoperative 1d and 7 d(P>0.05) and had significant differences in the postoperative 3 d, 5 d (P<0.05).All immunologic index had no significant differences in the postoperative 1d, 7d (P>0.05).Conclusion: The ALB content of patients with obstructive jaundice may decrease postoperatively. Treatment with hydroxylthy starch(130/0.4) can alleviate the drop of the ALB content. But it has no effects on immunologic function.