OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To compare the clinical efficacy of modified multi-side hole nasobiliary drainage(MHND)via the percuta-neous transhepatic cholangiography(PTC)route with traditional percutaneous transhepatic cholangial drainage(PTCD)for palliative treatment of patients with advanced obstructive cholangiocarcinoma.Methods A retrospective analysis was conducted on the data from 66 patients with advanced cholangiocarcinoma who underwent biliary drainage.Results Both groups normalize temperature and alleviate symptoms of acute cholangitis within 24 h post-puncture.There was no statistically significant difference in laboratory indicators such as white blood cell(WBC),total bilirubin(TBiL),alanine transaminase(ALT),aspartic transaminase(AST)at 48 h post-operation,and in the incidence of bile leakage,biliary peritonitis,and cholangitis during the postoperative hospital stay(P>0.05).However,the incidence of postoperative electrolyte disorders,gastrointestinal symptoms,and the recurrence rate of gastrointestinal symptoms during the follow-up period were significantly higher in the PTCD group compared to the MHND group,while the recur-rence rate of biliary tract infections was slightly higher in the MHND group compared to the PTCD group.The differences between the two groups were statistically significant(P<0.05).Conclusion Modified MHND shows better clinical efficacy in the treatment of patients with advanced tumor jaundice.Compared with traditional PTCD,it not only effectively reduces jaundice and relieves acute cholangitis but also significantly reduces gastrointestinal symptoms during the postoperative period,thereby improving the quality of life for patients.However,it is noteworthy that it may also increase the risk of biliary tract infections.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the effect of up-regulating tumor necrosis factor alpha induced protein 3(TNFAIP3)expression on hippocampal neurons in mice with cerebral ischemia-reperfusion.Methods The mice were randomly divided into 6 groups:sham group,sham empty vector group(sham-),sham TNFAIP3 high expression group(sham+),model group,model empty vector group(model-),model TNFAIP3 high expression group(model+).A mouse model of middle cerebral artery occlusion and cerebral ischemia-reperfusion was established using the suture method.After the successful establishment of the model,lentivirus was injected into the hippocampus 24 hours later.Two weeks later,samples were collected and Western blotting was used to detect the expressions of TNFAIP3 and ERK signaling pathway proteins.The changes in ischemic area were observed by 2,3,5-triphenyltetrazolium chloride(TTC)staining;HE staining was used to observe the morphological changes of hippocampal neurons,and ELISA was used to detect the expressions of lipoprotein-associated phospholipase A2(Lp-PLA2)and interleukin(IL)-8.Results The results of Western blotting indicated that the TNFAIP3 expression in the model group decreased significantly compared with the sham group(P＜0.05);Compared with the model group,there was no significant change in TNFAIP3 expression in the model-group(P＞0.05);The TNFAIP3 expression in the model+group increased significantly compared with the model group and model-group(P＜0.05).Compared with the sham group,the results of the sham+group showed that the ischemic area had no significant changes in TTC staining,and there were no significant changes in hippocampal neuronal morphology,and the expressions ERK signaling pathway proteins,Lp-PLA2 and IL-8(P＞0.05);Compared with the sham-and sham+groups,the model group showed an increase in ischemic area,significant damage to hippocampal neurons,a decrease in the number of Nissl bodies,and a significant increase in the expressions of ERK signaling pathway proteins,Lp-PLA2,and IL-8(P＜0.05);Compared to the model-group,the model+group showed a decrease in ischemic area,an increase in the number of neurons in the hippocampus and the number of Nissl bodies,and a significant decrease in the expressions of ERK signaling pathway proteins,Lp-PLA2,and IL-8(P＜0.05).Conclusion Up-regulation of TNFAIP3 may be one of the methods for repairing hippocampal neuronal damage caused by cerebral ischemia reperfusion.

Objective To compare the clinical efficacy of modified multi-side hole nasobiliary drainage(MHND)via the percuta-neous transhepatic cholangiography(PTC)route with traditional percutaneous transhepatic cholangial drainage(PTCD)for palliative treatment of patients with advanced obstructive cholangiocarcinoma.Methods A retrospective analysis was conducted on the data from 66 patients with advanced cholangiocarcinoma who underwent biliary drainage.Results Both groups normalize temperature and alleviate symptoms of acute cholangitis within 24 h post-puncture.There was no statistically significant difference in laboratory indicators such as white blood cell(WBC),total bilirubin(TBiL),alanine transaminase(ALT),aspartic transaminase(AST)at 48 h post-operation,and in the incidence of bile leakage,biliary peritonitis,and cholangitis during the postoperative hospital stay(P>0.05).However,the incidence of postoperative electrolyte disorders,gastrointestinal symptoms,and the recurrence rate of gastrointestinal symptoms during the follow-up period were significantly higher in the PTCD group compared to the MHND group,while the recur-rence rate of biliary tract infections was slightly higher in the MHND group compared to the PTCD group.The differences between the two groups were statistically significant(P<0.05).Conclusion Modified MHND shows better clinical efficacy in the treatment of patients with advanced tumor jaundice.Compared with traditional PTCD,it not only effectively reduces jaundice and relieves acute cholangitis but also significantly reduces gastrointestinal symptoms during the postoperative period,thereby improving the quality of life for patients.However,it is noteworthy that it may also increase the risk of biliary tract infections.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.