Objective:To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas.Methods:The clinical data of 61 patients who underwent colonoscopy in the People's Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group.According to the colonoscopy results,they were divided into control group(29 cases),non-adenomatous polyp group(12 cases),adenoma group(10 cases),colorectal cancer group(10 cases).17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group.Before bowel preparation for colonoscopy,the fecal samples were collected.Then the DNA of bacteria in the fecal samples was extracted.The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced.The species diversity of fecal flora was analyzed.Results:Alpha diversity analysis showed that the species diversity of samples from the high al-titude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group,and the species diversity of colorectal samples from the high al-titude colorectal cancer group was higher than that of the other two groups.While beta diversity showed no significant difference among the five groups.Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area,while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area.Differences were found in genus level analysis that the abundance of Bacteroides,Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area;the abundance of Blautia and Collinsella in the high altitude control group was the highest.Lacto-bacillus was not detected in the low altitude control group,while there was a highly significant difference(P＜0.05)in the level of Lactobacillus in the four groups of high altitude area,and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups.In the four groups of samples at high altitude,the abundance of Bifidobacterium decreased significantly,while the abundance of Christensenellaceae_R-7_group increased significantly.Conclusion:Compared with the high and low altitude controls,the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different.And the abundance of species are also diffe-rent at the phylum and genus levels,suggesting that altitude factors may have some influence on intestinal flora.

In recent years,the prevalence of porcine infectious pleuropneumonia caused by Actinoba-cillus pleuropneumoniae(APP)has significantly increased in large-scale pig farms in China.The i-solation,identification,and biological characteristic testing of newly prevalent strains have impor-tant clinical significance.This study isolated four suspected APP strains(named XB2T-56,JMTLP-443,YD-THB-755,SYZJ-291)from lung samples of pig farms suspected of outbreaks of porcine infectious pleuropneumonia in Hubei Province.They were identified by PCR amplification,and multiplex PCR serological typing,the biological properties were tested by detecting the growth a-bility,hemolytic activity and biofilm forming ability.The drug resistance of the strains was ana-lyzed by drug sensitivity testing,and the virulence of one strain(XB2T-56)in mice and piglets was evaluated.The PCR identification result showed that all four clinical isolates were APP serotype 15 strains.These four strains grew slower than serotype 1 standard strains,had weaker hemolytic activity,but could form stronger biofilms.These strains are all less sensitive to cephalosporin,tylo-sin,sulfamethoxazole,and doxycycline,but sensitive to cefotaxime and enrofloxacin.The mice and piglet infection experiments showed that the isolated strain XB2T-56 has strong virulence.Artifi-cial intranasal infection causes acute death in piglets,with typical symptoms of pleuropneumonia in the lungs,and serotype 15 strains can be isolated from the lesion site.This study indicates that the APP serotype 15 strain has strong virulence,providing new date for the clinical epidemiological characteristics of APP.

ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure （CHF） and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction （TAC）. Eight of the 50 SD rats were randomly selected as the sham group， and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model， trimetazidine （6.3 mg·kg^-1）， and Yiqi Wenyang Huoxue Lishui components （60 mg·kg^-1 total saponins of Astragali Radix， 10 mg·kg^-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma， 190 mg·kg^-1 aqueous extract of Lepidii Semen， and 100 mg·kg^-1 cinnamaldehyde） groups. The rats were administrated with corresponding agents by gavage， and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg^-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， hypersensitive troponin（cTnI）， creatine kinase （CK）， lactate dehydrogenase （LD）， free fatty acids （FFA）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The colorimetric assay was employed to measure the levels of adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta （ATP5D）， glucose transporter 4 （GLUT4）， and carnitine palmitoyltransferase-1 （CPT-1）. The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ. ResultsCompared with the sham group， the model group showed a loosening arrangement of cardiac fibers， fracture and necrosis of partial cardiac fibers， inflammatory cells in necrotic areas， massive blue fibrotic tissue in the myocardial interstitium， increased collagen fiber area and myocardial fibrosis， destroyed mitochondria， myofibril disarrangement， sparse myofilaments， and fractured and reduced cristae. In addition， the rats in the model group showed declined ejection fraction （EF） and fractional shortening （FS）， risen left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs）， elevated levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， lowered level of SOD， down-regulated protein levels of GLUT4 and CPT-1， decreased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and declined levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. Compared with the model group， the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue， risen EF and FS， declined LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs， lowered levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， elevated level of SOD， up-regulated protein levels of GLUT4 and CPT-1， increased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and elevated levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function， reduce myocardial injury， regulate glucose and lipid metabolism， optimize the utilization of substrates， and alleviate the damage of mitochondrial structure and function， thus improving the energy metabolism of the myocardium in the rat model of CHF.

In recent years,the prevalence of porcine infectious pleuropneumonia caused by Actinoba-cillus pleuropneumoniae(APP)has significantly increased in large-scale pig farms in China.The i-solation,identification,and biological characteristic testing of newly prevalent strains have impor-tant clinical significance.This study isolated four suspected APP strains(named XB2T-56,JMTLP-443,YD-THB-755,SYZJ-291)from lung samples of pig farms suspected of outbreaks of porcine infectious pleuropneumonia in Hubei Province.They were identified by PCR amplification,and multiplex PCR serological typing,the biological properties were tested by detecting the growth a-bility,hemolytic activity and biofilm forming ability.The drug resistance of the strains was ana-lyzed by drug sensitivity testing,and the virulence of one strain(XB2T-56)in mice and piglets was evaluated.The PCR identification result showed that all four clinical isolates were APP serotype 15 strains.These four strains grew slower than serotype 1 standard strains,had weaker hemolytic activity,but could form stronger biofilms.These strains are all less sensitive to cephalosporin,tylo-sin,sulfamethoxazole,and doxycycline,but sensitive to cefotaxime and enrofloxacin.The mice and piglet infection experiments showed that the isolated strain XB2T-56 has strong virulence.Artifi-cial intranasal infection causes acute death in piglets,with typical symptoms of pleuropneumonia in the lungs,and serotype 15 strains can be isolated from the lesion site.This study indicates that the APP serotype 15 strain has strong virulence,providing new date for the clinical epidemiological characteristics of APP.

Objective:Aural fullness（AF） is one of the common symptoms in ENT outpatient department, the incidence is about 1.4%. Some patients have an unknown etiology and are diagnosed as idiopathic ear congestion. In this paper, the therapeutic effect of gabapentin on some patients with idiopathic ear congestion was studied. Methods:Forty-eight cases of patients with ear distress as the main complaint between January 2024 and September 2024 were examined by questionnaire, specialist physical examination, pure tone audiometry and acoustic impedance. Among them, 19 cases were diagnosed with definite etiology, 29 cases were diagnosed with idiopathic ear congestion, and 7 cases were lost to follow-up in the idiopathic ear congestion group. Twenty-two patients were divided into the administration group（12 cases receiving regular gabapentin treatment for 3-6 weeks） and the control group（10 cases receiving no medication） based on whether they received gabapentin to explore the effect of ear congestion and possible related factors. Results:Among the 12 patients in the medication group, 2 cases of aural fullness disappeared completely, 9 cases had different degrees of relief, and 1 case had no relief Among the 10 patients in the control group, 2 patients' aural fullness disappeared, 1 patient consciously relieved, and the remaining 7 patients had no significant change in ear boredom. According to the Wong-baker Facial expression Scale, the score of ear tightness decreased from 2.83 before medication to 1.51 after medication in the medication group. The remission rate of ear congestion in the medication group was significantly higher than that in the control group（P=0.004）. Conclusion:Gabapentin can be used to treat idiopathic aural fullness, which can reduce the symptoms effectively. This suggests that the occurrence of idiopathic aural fullness may be related to neuralgia and central sensitization.
Humans ; Gabapentin/therapeutic use* ; Amines/therapeutic use* ; gamma-Aminobutyric Acid/therapeutic use* ; Female ; Male ; Cyclohexanecarboxylic Acids/therapeutic use* ; Ear Diseases/drug therapy* ; Middle Aged ; Adult ; Aged

Objective:To investigate the impact of chromate exposure on pulmonary function indices in occupational populations and explore the potential role of alterations in inflammatory indicators in this process.Methods:In July 2024, A cross-sectional analysis was conducted using occupational health examination data of 30875 workers from chromate-related enterprises in Jiangsu Province in 2020 and 2021. Based on the occupational positions and whether there is chromium acid salt exposure in the occupational hazards of the research subjects over the years, they are divided into chromium acid salt exposure group and non-exposure group. For those exposed to chromium acid salts, based on job position descriptions and duration of chromium acid salt exposure, they are further categorized into intermittent exposure group and continuous exposure group; among them, the actual exposure time in the intermittent exposure group is less than half of the working shift time, and the exposure duration is less than the total working life. Pulmonary function test indicators include forced vital capacity (forced vital capacity, FVC) %, first-second forced expiratory volume (forced expiratory volume in one second, FEV 1.0) %, and the ratio of first-second forced expiratory volume to forced vital capacity (FEV 1.0/FVC) %. Peripheral blood samples from the upper limbs of the research subjects were collected on an empty stomach for routine blood tests, selecting neutrophil count, platelet count, and lymphocyte count results, calculating the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Quantitative data that meet normal distribution are expressed using Mean±SD, while variables that do not meet normal distribution are represented by M ( Q1, Q3). Categorical data are expressed using frequency or proportion (%). Linear variable comparisons between groups use t-tests. Generalized linear models were employed to assess the correlation between chromate exposure and pulmonary function indices, while mixed regression models were utilized to explore potential underlying effects. Results:Compared with the non-exposed group, the pulmonary function indices FVC (%), FEV 1.0/FVC (%), and FEV 1.0 (%) in the chromate-exposed group showed a decreasing trend ( P<0.01), indicating statistically significant differences. As the frequency of chromate exposure increased, the prevalence of pulmonary dysfunction rose. The prevalence rates of obstructive, restrictive, and mixed respiratory dysfunction among the chromate-exposed population (including intermittent exposure and continuous exposure groups) were 0.26%, 4.67%, and 0.12%, which were higher than those in the non-exposed group (0.09%, 0.84%, and 0.07%, respectively). All these differences were statistically significant ( P<0.05). After stratification by gender, a negative correlation was observed between chromate exposure and the inflammatory indicator platelet-to-lymphocyte ratio (PLR) ( P<0.05). Potential effect analysis revealed that PLR played a certain mediating role between chromate exposure and the decline in pulmonary function indices, with a mediating proportion of 2.2%. Conclusion:Chromate exposure in occupational populations may lead to a decline in pulmonary ventilatory function and alterations in peripheral blood inflammatory indicators. Inflammatory indicators may be involved in the pulmonary function decline caused by chromate exposure.

Objective:To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas.Methods:The clinical data of 61 patients who underwent colonoscopy in the People's Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group.According to the colonoscopy results,they were divided into control group(29 cases),non-adenomatous polyp group(12 cases),adenoma group(10 cases),colorectal cancer group(10 cases).17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group.Before bowel preparation for colonoscopy,the fecal samples were collected.Then the DNA of bacteria in the fecal samples was extracted.The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced.The species diversity of fecal flora was analyzed.Results:Alpha diversity analysis showed that the species diversity of samples from the high al-titude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group,and the species diversity of colorectal samples from the high al-titude colorectal cancer group was higher than that of the other two groups.While beta diversity showed no significant difference among the five groups.Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area,while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area.Differences were found in genus level analysis that the abundance of Bacteroides,Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area;the abundance of Blautia and Collinsella in the high altitude control group was the highest.Lacto-bacillus was not detected in the low altitude control group,while there was a highly significant difference(P＜0.05)in the level of Lactobacillus in the four groups of high altitude area,and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups.In the four groups of samples at high altitude,the abundance of Bifidobacterium decreased significantly,while the abundance of Christensenellaceae_R-7_group increased significantly.Conclusion:Compared with the high and low altitude controls,the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different.And the abundance of species are also diffe-rent at the phylum and genus levels,suggesting that altitude factors may have some influence on intestinal flora.

Objective:To investigate the impact of chromate exposure on pulmonary function indices in occupational populations and explore the potential role of alterations in inflammatory indicators in this process.Methods:In July 2024, A cross-sectional analysis was conducted using occupational health examination data of 30875 workers from chromate-related enterprises in Jiangsu Province in 2020 and 2021. Based on the occupational positions and whether there is chromium acid salt exposure in the occupational hazards of the research subjects over the years, they are divided into chromium acid salt exposure group and non-exposure group. For those exposed to chromium acid salts, based on job position descriptions and duration of chromium acid salt exposure, they are further categorized into intermittent exposure group and continuous exposure group; among them, the actual exposure time in the intermittent exposure group is less than half of the working shift time, and the exposure duration is less than the total working life. Pulmonary function test indicators include forced vital capacity (forced vital capacity, FVC) %, first-second forced expiratory volume (forced expiratory volume in one second, FEV 1.0) %, and the ratio of first-second forced expiratory volume to forced vital capacity (FEV 1.0/FVC) %. Peripheral blood samples from the upper limbs of the research subjects were collected on an empty stomach for routine blood tests, selecting neutrophil count, platelet count, and lymphocyte count results, calculating the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Quantitative data that meet normal distribution are expressed using Mean±SD, while variables that do not meet normal distribution are represented by M ( Q1, Q3). Categorical data are expressed using frequency or proportion (%). Linear variable comparisons between groups use t-tests. Generalized linear models were employed to assess the correlation between chromate exposure and pulmonary function indices, while mixed regression models were utilized to explore potential underlying effects. Results:Compared with the non-exposed group, the pulmonary function indices FVC (%), FEV 1.0/FVC (%), and FEV 1.0 (%) in the chromate-exposed group showed a decreasing trend ( P<0.01), indicating statistically significant differences. As the frequency of chromate exposure increased, the prevalence of pulmonary dysfunction rose. The prevalence rates of obstructive, restrictive, and mixed respiratory dysfunction among the chromate-exposed population (including intermittent exposure and continuous exposure groups) were 0.26%, 4.67%, and 0.12%, which were higher than those in the non-exposed group (0.09%, 0.84%, and 0.07%, respectively). All these differences were statistically significant ( P<0.05). After stratification by gender, a negative correlation was observed between chromate exposure and the inflammatory indicator platelet-to-lymphocyte ratio (PLR) ( P<0.05). Potential effect analysis revealed that PLR played a certain mediating role between chromate exposure and the decline in pulmonary function indices, with a mediating proportion of 2.2%. Conclusion:Chromate exposure in occupational populations may lead to a decline in pulmonary ventilatory function and alterations in peripheral blood inflammatory indicators. Inflammatory indicators may be involved in the pulmonary function decline caused by chromate exposure.

Objective:To explore the adverse cardiac event risk signals in arsenical for injection, improve the clinical understanding of the cardiac toxicity of arsenical.Methods:The risk signals of adverse cardiac events associated with arsenical for injection were mined using 3 methods, including reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, and the Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method based on data in Shandong Provincial Center of Adverse Drug Reaction Monitoring (Shandong data) in China from the first quarter of 2003 to the fourth quarter of 2022 and the data in US FDA Adverse Event Reporting System (FAERS) database from the fourth quarter of 2003 to the third quarter of 2023. The definition of risk signal in ROR and PRR method was the number of adverse event reports ≥3 and the lower limit of 95% confidence interval ( CI) of ROR and PRR >1. The definition of risk signals in MHRA comprehensive standard method was the number of adverse event reports ≥3, PRR>2, and χ2>4. Results:There were a total of 358 reports on arsenical for injection in Shandong data, of which 275 (76.8%) were related to arsenious acid and sodium chloride injection, and 83 (23.2%) were related to arsenic trioxide for injection. Among the 358 reports, adverse cardiac reactions were reported in 25 reports (7.0%), and severe cases accounted for 28.0% (7/25). There were a total of 1 294 reports on ATO in FAERS, and adverse cardiac events were reported in 418 reports (32.3%), of which severe cases accounted for 62.2% (260/418). The signal mining results form 275 reports on arsenious acid and sodium chloride injection in Shandong data showed that QT interval prolonged, chest tightness, cardiopalmus, and palpitations were risk signals. Among them, the signal strength of QT interval prolonged was the strongest. A total of 35 adverse cardiac event signals were mined in FAERS data, of which the signal strength of QT interval prolonged and long QT syndrome were the strongest. In addition, the strength of 6 arrhythmia signals (bradyarrhythmia, supraventricular premature contraction, ventricular premature contraction, torsade de pointes, ventricular tachycardia, and atrioventricular block) and 6 cardiac organic lesion signals (pericarditis, endocarditis, pericardial effusion, myocarditis, mitral regurgitation, and cardiac enlargement) also ranked high.Conclusions:Arsenical for injection is strongly associated with cardiotoxicity, and the proportion of severe cases is relatively high. The cardiotoxicity mainly affects the QT interval, and can also manifest as various types of arrhythmias and some cardiac organic lesions.

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.