OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

Objective This study aims to explore the association between non-suicidal self-injury(NSSI)and suicide attempts(SA)in adolescents and the mediating effect of cognitive flexibility.Methods A total of 218 depression patients with NSSI who met the Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)diagnostic criteria for NSSI were enrolled.Patients were divided into SA group(n=105)and non-SA group(n=113)according to the presence or absence of SA in the last one year.The adolescent non-suicidal self-injury assessment questionnaire(ANSAQ)and the Wisconsin card sorting tests(WCST)was used to assess the frequency of NSSI and cognitive flexibility,respectively.A mediation model was constructed to conduct path analysis,and the product distribution method was utilized to test the mediation effect.Results The difference between SA group and non-SA group in NSSI(20.1±10.7 vs.14.7±9.1)and WCST scores[correct responses percentage(67.3％±14.2％vs.72.9％±12.2％),error responses(39.8±20.3 vs.31.6±17.9),perseverative response(6.7±3.8 vs.5.3±2.9),and non-perseverative errors(37.6±21.0 vs.28.9±18.1)]were significant(P<0.05).Dichotomous logistic regression analysis showed that the frequency of NSSI(OR=1.051,95％CI:1.021-1.082)and the score of perseverative response(OR=1.100,95％CI:1.008-1.199)were significantly associated with suicidal behavior among adolescents with NSSI(P<0.05).Moreover,perseverative response partially mediated the association between NSSI and SA(95％CI of Za×Zb:0.0003-0.0168).Conclusion High NSSI and low cognitive flexibility are risk factors for suicide attempts in NSSI adolescents and NSSI may also affect SA indirectly by lowering cognitive flexibility.

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

Objective This study aims to explore the association between non-suicidal self-injury(NSSI)and suicide attempts(SA)in adolescents and the mediating effect of cognitive flexibility.Methods A total of 218 depression patients with NSSI who met the Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)diagnostic criteria for NSSI were enrolled.Patients were divided into SA group(n=105)and non-SA group(n=113)according to the presence or absence of SA in the last one year.The adolescent non-suicidal self-injury assessment questionnaire(ANSAQ)and the Wisconsin card sorting tests(WCST)was used to assess the frequency of NSSI and cognitive flexibility,respectively.A mediation model was constructed to conduct path analysis,and the product distribution method was utilized to test the mediation effect.Results The difference between SA group and non-SA group in NSSI(20.1±10.7 vs.14.7±9.1)and WCST scores[correct responses percentage(67.3％±14.2％vs.72.9％±12.2％),error responses(39.8±20.3 vs.31.6±17.9),perseverative response(6.7±3.8 vs.5.3±2.9),and non-perseverative errors(37.6±21.0 vs.28.9±18.1)]were significant(P<0.05).Dichotomous logistic regression analysis showed that the frequency of NSSI(OR=1.051,95％CI:1.021-1.082)and the score of perseverative response(OR=1.100,95％CI:1.008-1.199)were significantly associated with suicidal behavior among adolescents with NSSI(P<0.05).Moreover,perseverative response partially mediated the association between NSSI and SA(95％CI of Za×Zb:0.0003-0.0168).Conclusion High NSSI and low cognitive flexibility are risk factors for suicide attempts in NSSI adolescents and NSSI may also affect SA indirectly by lowering cognitive flexibility.

ObjectiveTo observe the clinical effectiveness of midnight-noon ebb-low acupuncture by hour-prescription of points combined with western medicine for patients of Parkinson's disease with restless legs syndrome. MethodsSixty cases of Parkinson's disease with restless legs syndrome were divided into a control group and a treatment group randomly， with 30 cases in each group. The control group was given conventional western medicine treatment， and the treatment group was given the treatment of the control group with midnight-noon ebb-low acupuncture by hour-prescription of points based on Daling （PC 7）， Zhongzhu （TE 3）， Yanglingquan （GB 34）， Zusanli （ST 36）， and Sanyinjiao （SP 6） with perpendicular insertion， and Baihui （GV 20） with oblique insertion to the back，all of them used the manipulation of neutral reinforcement and reduction； Dudu （SP 2） and Taibai （SP 3） acupoints were inserted in accordance with the direction of the meridian travelling when the patients inhaled， and the needle was removed when exhaled； the time of acupuncture manipulation selected as Si time （9 AM-11 AM）， the needle stay for 30 mins each time， once a day， 5 times a week， a total of 4 weeks of treatment. The international restless legs severity scale （IRLSS）， Pittsburgh sleep quality index （PSQI）， Parkinson's disease quality of life questionnaire （PDQ-39）， and the International Movement Disorder Society unified Parkinson's disease rating scale part Ⅰ （MDS-UPDRS Ⅰ） were compared before and after the treatment， and the clinical effectiveness of the two groups were compared after the treatment. ResultsIRLSS scores， PSQI scores， PDQ-39 scores and MDS-UPDRS Ⅰ scores decreased in both groups after treatment compared to those before treatment （P＜0.05 or P＜0.01）. After treatment， the total effective rate in the treatment group （83.3%， 25/30） was higher than that in the control group （60%， 18/30） （P＜0.05）. ConclusionAdding midnight-noon ebb-low acupuncture with hour-prescription of points on conventional western medicine treatment for Parkinson's disease with restless legs syndrome can significantly improve patients' clinical symptoms， sleep quality， quality of life， and enhance clinical effectiveness.

Objective:To analyze the effect of percutaneous transluminal angioplasty (PTA) in the treatment of autogenous arteriovenous fistula (AVF) stenosis and influcing factors of restenosis/loss of function after PTA.Methods:The medical records of 104 patients with AVF stenosis treated by PTA in People′s Hospital of Huadu District from March 2019 to July 2020 and the 1-year follow-up were retrospectively analyzed. Kaplan-meier curves were used to analyze the primary patency rates at 3 months, 6 months and 1 year. COX regression was used to analyze the influencing factors of restenosis/loss of function after PTA.Results:The primary patency rates of AVF at 3, 6 and 12 months after PTA were 86.2%, 83.2% and 64.7%, respectively. Guide wire entry into the distal end of radial artery, the use of two balloons in stepwise mode, postoperative dilatation diameter, and dialysis blood flow after PTA were independent risk factors for restenosis/loss of fuction after PTA for AVF stenosis (all P<0.05). Conclusions:The guide wire into the distal end of the artery and passive use of more than two balloons are important factors affecting AVF restenosis/loss of function after PTA .

A 62-year-old male patient received aspirin, clopidogrel, and atorvastatin calcium after percutaneous coronary intervention for coronary atherosclerotic heart disease. One week later, the patient received anti- Helicobacter pylori (Hp) therapy with amoxicillin capsules, clarithromycin tablets, bismuth tartrate capsules, and pantoprazole sodium enteric coated tablets due to Hp infection, and two to three days after taking the drugs, the patient developed systemic fatigue, nausea, joint discomfort and muscle soreness, which were gradually aggravated. Laboratory tests showed muscle hemoglobin (MYO)>1 000 μg/L, serum creatinine (Scr) 69 mmol/L, urea nitrogen (BUN) 3.5 mmol/L, alkaline phosphatase (ALP) 148 U/L, alanine aminotransferase (ALT) 750 U/L, aspartate aminotransferase (AST) 850 U/L, g-glutamyl transpeptidase (γ-GT) 181 U/L, lactate dehydrogenase (LDH) 1 177 U/L, creatine kinase (CK) 8 144 U/L, CK-MB 255 U/L. Atorvastatin calcium was stopped, and symptomatic and supportive treatments such as alkalized urine and fluid replacement were given, and anti-Hp treatments were continued. However, the CK level was continued to increase. CK reached 15 794 U/L 4 days after atorvastatin calcium discontinuation. It was considered that the patient′s rhabdomyolysis might be related to interaction between atorvastatin calcium and clarithromycin. Then the anti-Hp drugs were discontinued. On the 2nd of drug withdrawal, the patients′ muscle soreness was alleviated than before; on the 4th day, CK and other serum enzymology indexes began to decline; on the 8th day, the patient′s fatigue and muscle soreness completely disappeared, with CK 908 U/L; on the 15th day, ALT was 105 U/L, AST was 42 U/L, γ-GT was 107 U/L, CK was 143 U/L, CK-MB was 29 U/L, and LDH was 339 U/L; 5 weeks later, the patient took atorvastatin again, myalgia and fatigue did not recur, and no abnormality was found in blood biochemical indexes.

A 62-year-old male patient received aspirin, clopidogrel, and atorvastatin calcium after percutaneous coronary intervention for coronary atherosclerotic heart disease. One week later, the patient received anti- Helicobacter pylori (Hp) therapy with amoxicillin capsules, clarithromycin tablets, bismuth tartrate capsules, and pantoprazole sodium enteric coated tablets due to Hp infection, and two to three days after taking the drugs, the patient developed systemic fatigue, nausea, joint discomfort and muscle soreness, which were gradually aggravated. Laboratory tests showed muscle hemoglobin (MYO)>1 000 μg/L, serum creatinine (Scr) 69 mmol/L, urea nitrogen (BUN) 3.5 mmol/L, alkaline phosphatase (ALP) 148 U/L, alanine aminotransferase (ALT) 750 U/L, aspartate aminotransferase (AST) 850 U/L, g-glutamyl transpeptidase (γ-GT) 181 U/L, lactate dehydrogenase (LDH) 1 177 U/L, creatine kinase (CK) 8 144 U/L, CK-MB 255 U/L. Atorvastatin calcium was stopped, and symptomatic and supportive treatments such as alkalized urine and fluid replacement were given, and anti-Hp treatments were continued. However, the CK level was continued to increase. CK reached 15 794 U/L 4 days after atorvastatin calcium discontinuation. It was considered that the patient′s rhabdomyolysis might be related to interaction between atorvastatin calcium and clarithromycin. Then the anti-Hp drugs were discontinued. On the 2nd of drug withdrawal, the patients′ muscle soreness was alleviated than before; on the 4th day, CK and other serum enzymology indexes began to decline; on the 8th day, the patient′s fatigue and muscle soreness completely disappeared, with CK 908 U/L; on the 15th day, ALT was 105 U/L, AST was 42 U/L, γ-GT was 107 U/L, CK was 143 U/L, CK-MB was 29 U/L, and LDH was 339 U/L; 5 weeks later, the patient took atorvastatin again, myalgia and fatigue did not recur, and no abnormality was found in blood biochemical indexes.

Objective:To identify the pathogenic gene mutations in a family with early onset severe retinal dystrophy (EOSRD).Methods:A retrospective clinical study. One patient and three family members from a Han of EOSRD who were diagnosed at Henan Eye Hospital in August 2018 were included in the study. After the detailed history of the patients was collected, all participants underwent best corrected visual acuity (BCVA), slit-lamp, fundus biomicroscopy with the slit lamp, untra-widefield fundus color photography, spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ff-ERG). The subject’s peripheral venous blood of 5 ml was collected and the whole genome DNA was extracted. A genetic eye disease capture chip containing 441 disease-causing genes was used for targeted capture and enrichment of high-throughput sequencing, and Sanger sequencing was performed for the clear pathogenic mutation sites; the analysis software was used for bioinformatics analysis of the mutation sites.Results:A 6-year-old female proband developed poor night vision in both eyes after 1 year old. The BCVA of both eyes were 0.1. The color of the optic disc was slightly lighter; the diameter of the retinal vessels was slightly reduced, and extensive pigment changes can be seen in the retina outside the vascular arch. SD-OCT examination showed that the outer membrane, ellipsoid zone and chimera zone in the central fovea of both eyes were unclear and intermittent. The visual area outside the fovea was neuroepithelial outer plexiform layer, outer nuclear layer, outer membrane, ellipsoid zone. The chimera zone gradually disappeared, and the thickness of the pigment epithelial layer was not uniform. In ff-ERG examination, the functions of the binocular cone and rod system were severely decreased. The results of genetic testing showed that there were c.921C>A homozygous mutations in the Tubby-like protein (TULP1) gene of the proband, and c.3121C>T and c.3488G>A compound heterozygous mutations in the cyclic nucleotide gated channel beta 1 (CNGB1) gene. Amino acid conservation analysis results showed that the above three mutation sites were highly conserved in multiple species; bioinformatics analysis results showed that TULP1 gene c.921C>A (p.Cys307*) had translation termination in the protein conserved region, CNGB1 gene c.3121C>T (p.Arg1041Trp) and c.3488G>A (p.Gly1163Glu) had amino acid polarity changes in the protein conserved region, which led to major changes in the protein spatial structure.Conclusion:TULP1 gene c.921C>A homozygous mutation, CNGB1 gene c.3121C>T and c.3488G>A compound heterozygous mutation are the mutation sites of this EOSRD family.