Xiao’er Guangpu Zhixie Oral Liquid (XeGp) is clinically used to treat pediatric diarrhea attributed to dampness encumbering the spleen, but its efficacy against bacterial diarrhea has not been fully established. In this study, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of XeGp against Salmonella Typhimurium SL1344 were determined using a microplate assay and a viable plate count method. A mouse model of bacterial diarrhea was also established to evaluate its antidiarrheal effects. The results showed that the MIC and MBC of XeGp against SL1344 corresponded to 1:20 and 1:10 dilutions, respectively. In an SL1344-induced mouse model of diarrhea, XeGp alleviated diarrhea symptoms, reduced the diarrhea index, attenuated diarrhea-associated body weight loss, and ameliorated intestinal histopathological damage caused by bacterial infection. These effects may be associated with reduced expression of TLR4 and phosphorylated NF-κB (p-NF-κB) in colonic tissues, increased expression of the tight junction proteins ZO-1 and occludin in intestinal tissues, and elevated secretory immunoglobulin A (sIgA) levels in the small intestinal mucosa. In addition, XeGp treatment had no significant effect on intestinal microbial diversity and partially restored the reductions in the total numbers of Lactobacillus and Bifidobacteriumcaused by Salmonella infection. When administered in combination with cefixime granules, XeGp enhanced, to some extent, the effects of cefixime granules in alleviating diarrhea, intestinal inflammation, and tissue injury caused by infection. It also partially ameliorated the intestinal microbiota dysbiosis induced by continuous cefixime treatment. In conclusion, XeGp has certain therapeutic effects on bacterial diarrhea caused by S. Typhimurium, providing a scientific basis for its clinical application.

OBJECTIVE To investigate the efficacy and safety of metformin in the treatment of diabetes mellitus type 2 （T2DM） complicated with sarcopenia in elderly patients. METHODS From January 2022 to January 2024， clinical data from eligible patients with T2DM complicated with sarcopenia treated at the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College were collected. Patients were randomly assigned into control group （70 cases） and observation group （70 cases） using a random number table. Both groups received routine interventions； control group additionally received subcutaneous injections of Insulin glargine injection before bedtime and Human insulin injection 30 minutes before breakfast， lunch and dinner every day. In addition to the same treatments as the control group， the observation group was administered 0.5 g of Metformin hydrochloride sustained-release tablets orally once daily. Both groups were treated continuously for 24 weeks. Comparisons were made between the two groups in terms of glucose metabolism indexes [fasting blood glucose （FBG）， 2 h postprandial blood glucose （2 hBG）， and glycosylated hemoglobin （HbA1c）]， homeostasis model assessment of insulin resistance （HOMA-IR）， appendicular skeletal mass muscle index （ASMI）， grip strength， walking speed， lipid metabolism indexes [serum total triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， serological markers [high-sensitivity C reactive protein （hs-CRP）， interleukin-6 （IL-6）， and ferritin levels] and quality of life. The occurrence of ADR was recorded in both groups. RESULTS 65 patients in the control group and 63 patients in the observation group completed this study， respectively. After treatment， the levels of FBG， 2 hBG， HbA1c， HOMA-IR，TG and TC in both groups， and the levels of hs-CRP， IL-6 and ferritin in observation group were all significantly reduced compared to those before treatment （P＜0.05）， and the HOMA-IR in observation group was significantly lower than control group （P＜0.05）； additionally， the grip strength， walking speed， and scores for daily living and activity abilities of observation group were increased than those before treatment and the control group （P＜0.05）. The incidence of adverse drug reactions in both groups was 2.86%. CONCLUSIONS Metformin can reduce inflammatory factors and ferritin levels， promote the recovery of muscle mass and strength， improve insulin resistance， and quality of life in elderly patients with T2DM complicated with sarcopenia， and does not increase the occurrence of adverse drug reactions.

The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson's disease (PD). In this study, wild-type AB zebrafish and transgenic Tg ( vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
Animals ; Zebrafish ; Signal Transduction/drug effects* ; Animals, Genetically Modified ; Dopamine/metabolism* ; Neuroprotective Agents/pharmacology* ; Disease Models, Animal ; Camphanes/pharmacology* ; Ubiquinone/pharmacology* ; Parkinson Disease/drug therapy* ; Dopaminergic Neurons/metabolism*

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

Objective To compare the clinical efficacy of intraoperative intravenous tirofiban versus preoperative loading dose dual antiplatelet therapy in the acute phase LVIS stent-assisted coil embolization treatment for ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured,wide-neck intracranial aneurysms underwent LVIS stent-assisted coil embolization in the Department of Neurosurgery at Heze Municipal Hospital were retrospectively and consecutively enrolled from January 2017 to June 2023.According to the Chinese expert consensus on antiplatelet therapy for intracranial aneurysms,patients were divided into two groups based on the types of antiplatelet therapy they received:the loading-dose dual antiplatelet therapy(DAPT)group and the tirofiban group.Baseline and clinical data were collected and compared between the two groups,including age,sex,hypertension,diabetes mellitus,coronary artery disease,history of cerebral hemorrhage,preoperative Hunt-Hess grade,maximum aneurysm diameter,aneurysm neck width,and aneurysm location.Perioperative ischemic and hemorrhagic complications were collected and compared between the two groups.Perioperative ischemic complications included:intraoperative stent thrombosis(defined as filling defects in the parent artery,and,occlusion of the parent artery or stented branch during the procedure),and symptomatic ischemic infarction within 24 h postoperatively(confirmed by imaging with corresponding neurological deficits).Perioperative hemorrhagic complications included:intraoperative rupture of the target aneurysm(contrast extravasation or acute hemorrhage during embolization)and intracranial hemorrhage within 24 h postoperatively(new or worsened subarachnoid hemorrhage or intraparenchymal hemorrhage on CT).Clinical outcomes at 90 days were collected via telephone or outpatient follow-up,and evaluated using favorable prognosis defined as modified Rankin scale(mRS).A mRS score of 0-2 were defined as favorable prognosis and 3-6 as poor prognosis.Six-month postoperative imaging follow-up were collected,angiographic outcomes were categorized into four groups based on comparison with immediate post-embolization results:complete occlusion,total absence of contrast filling in the aneurysm sac;improved,reduced contrast filling;stable,unchanged contrast filling;and,recurrence,increased contrast filling.Results Totals of 108 patients with intracranial aneurysms treated by LVIS stent-assisted coiling were enrolled,with 30 males and 78females,aged32-75years(median age63[50,66]years).Among the108cases,55cases were assigned into the DAPT group,and 53 cases were included in the tirofiban group.(1)No statistically significant differences were observed between the tirofiban group and the DAPT group in baseline and clinical characteristics(all P＞0.05).(2)All patients underwent successful LVIS stent-assisted coiling,with a technical success rate of 100%.The total perioperative ischemic complications were 12.0%(13/108),including 4.6%(5/108)intraoperative stent thrombosis and 7.4%(8/108)symptomatic ischemic infarction within 24h after surgery.The total perioperative hemorrhagic complications rate was 1.9%(2/108),including 1 case of intraoperative aneurysm rupture and 1 case of postoperative intracranial hemorrhage within24h.92.6%(100/108)of the patients exhibited favorable prognosis and 7.4%(8/108)showed poor prognosis at the 90-day follow-ups.78.7%(85/108)of the patients accomplished at 6-month imaging follow-ups,the complete occlusion ratio was 94.1%(80/85)and the recurrence ratio was 2.4%(2/85).(3)The overall perioperative ischemic complication rates were 13.2%(7/53)in the tirofiban group and 10.9%(6/55)in the DAPT group,with no statistically significant difference(P=0.720).Intraoperative stent thrombosis occurred more frequently in the DAPT group(9.1%[5/55]vs.0,P=0.025),while symptomatic ischemic infarction within 24 h post-procedure was lower in the DAPT group(1.8%[1/55]vs.13.2%[7/53],P=0.028).The hemorrhagic complications occurred only in the DAPT group,with a rate of 3.6%(2/55),while no events observed in the tirofiban group.At the 90-day follow-up,the proportion of patients with favorable outcomes was 94.3%(50/53)in the tirofiban group and 90.9%(50/55)in the DAPT group,with no statistically significant difference between the groups(P=0.754).Conclusions Both intraoperative intravenous tirofiban and preoperative loading-dose DAPT demonstrated comparable safety profile and favorable clinical efficacy in the acute-phase treatment of ruptured wide-necked intracranial aneurysms with LVIS stent-assisted coil embolization.The results require further validation through large-scale prospective studies.

Objective To compare the clinical efficacy of intraoperative intravenous tirofiban versus preoperative loading dose dual antiplatelet therapy in the acute phase LVIS stent-assisted coil embolization treatment for ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured,wide-neck intracranial aneurysms underwent LVIS stent-assisted coil embolization in the Department of Neurosurgery at Heze Municipal Hospital were retrospectively and consecutively enrolled from January 2017 to June 2023.According to the Chinese expert consensus on antiplatelet therapy for intracranial aneurysms,patients were divided into two groups based on the types of antiplatelet therapy they received:the loading-dose dual antiplatelet therapy(DAPT)group and the tirofiban group.Baseline and clinical data were collected and compared between the two groups,including age,sex,hypertension,diabetes mellitus,coronary artery disease,history of cerebral hemorrhage,preoperative Hunt-Hess grade,maximum aneurysm diameter,aneurysm neck width,and aneurysm location.Perioperative ischemic and hemorrhagic complications were collected and compared between the two groups.Perioperative ischemic complications included:intraoperative stent thrombosis(defined as filling defects in the parent artery,and,occlusion of the parent artery or stented branch during the procedure),and symptomatic ischemic infarction within 24 h postoperatively(confirmed by imaging with corresponding neurological deficits).Perioperative hemorrhagic complications included:intraoperative rupture of the target aneurysm(contrast extravasation or acute hemorrhage during embolization)and intracranial hemorrhage within 24 h postoperatively(new or worsened subarachnoid hemorrhage or intraparenchymal hemorrhage on CT).Clinical outcomes at 90 days were collected via telephone or outpatient follow-up,and evaluated using favorable prognosis defined as modified Rankin scale(mRS).A mRS score of 0-2 were defined as favorable prognosis and 3-6 as poor prognosis.Six-month postoperative imaging follow-up were collected,angiographic outcomes were categorized into four groups based on comparison with immediate post-embolization results:complete occlusion,total absence of contrast filling in the aneurysm sac;improved,reduced contrast filling;stable,unchanged contrast filling;and,recurrence,increased contrast filling.Results Totals of 108 patients with intracranial aneurysms treated by LVIS stent-assisted coiling were enrolled,with 30 males and 78females,aged32-75years(median age63[50,66]years).Among the108cases,55cases were assigned into the DAPT group,and 53 cases were included in the tirofiban group.(1)No statistically significant differences were observed between the tirofiban group and the DAPT group in baseline and clinical characteristics(all P＞0.05).(2)All patients underwent successful LVIS stent-assisted coiling,with a technical success rate of 100%.The total perioperative ischemic complications were 12.0%(13/108),including 4.6%(5/108)intraoperative stent thrombosis and 7.4%(8/108)symptomatic ischemic infarction within 24h after surgery.The total perioperative hemorrhagic complications rate was 1.9%(2/108),including 1 case of intraoperative aneurysm rupture and 1 case of postoperative intracranial hemorrhage within24h.92.6%(100/108)of the patients exhibited favorable prognosis and 7.4%(8/108)showed poor prognosis at the 90-day follow-ups.78.7%(85/108)of the patients accomplished at 6-month imaging follow-ups,the complete occlusion ratio was 94.1%(80/85)and the recurrence ratio was 2.4%(2/85).(3)The overall perioperative ischemic complication rates were 13.2%(7/53)in the tirofiban group and 10.9%(6/55)in the DAPT group,with no statistically significant difference(P=0.720).Intraoperative stent thrombosis occurred more frequently in the DAPT group(9.1%[5/55]vs.0,P=0.025),while symptomatic ischemic infarction within 24 h post-procedure was lower in the DAPT group(1.8%[1/55]vs.13.2%[7/53],P=0.028).The hemorrhagic complications occurred only in the DAPT group,with a rate of 3.6%(2/55),while no events observed in the tirofiban group.At the 90-day follow-up,the proportion of patients with favorable outcomes was 94.3%(50/53)in the tirofiban group and 90.9%(50/55)in the DAPT group,with no statistically significant difference between the groups(P=0.754).Conclusions Both intraoperative intravenous tirofiban and preoperative loading-dose DAPT demonstrated comparable safety profile and favorable clinical efficacy in the acute-phase treatment of ruptured wide-necked intracranial aneurysms with LVIS stent-assisted coil embolization.The results require further validation through large-scale prospective studies.

Endovascular aneurysm repair(EVAR)is the most common treatment for abdominal aortic aneurysm.However,when the common iliac artery has expansion or aneurysm,there may be internal leakage at the distal end of the stent.In this case,the ideal endovascular repair should ensure the pelvic blood supply on the premise of complete exclu-sion of the aneurysm.It is feasible and safe to use iliac branch devices(IBD)to preserve unilateral or bilateral internal iliac arteries,and its technology and clinical results are equivalent to standard EVAR.But IBD has certain anatomical a-daptability.In this paper,the current status of preservation of internal iliac artery with IBD is systematically reviewed.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.