Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To summarize the drug resistance characteristics of clinical pathogen isolates in a tuberculosis specialized hospital from 2017 to 2023，and understand the distribution characterisitics of pathogens and their resistance to antimicrobial agents.Methods:The isolates from January 2017 to December 2023 were identified and subjected to drug susceptibility tests using the VITEK 2-compact system. The susceptibilities of the isolates to antimicrobial agents were determined by the minimum inhibitory concentration（MIC）methods according to the CLSI（2023）guideline. The data of detection of different kinds of bacteria，specimen distribution and the detection rates of major drug-resistant gram-negative bacteria in hospital antimicrobial resistance were analyzed. Chi square test were performed to analyze one or more sets of data related to detection rate or drug resistance rate by SPSS 17.0.Results:A total of 9 993 isolates were detected，among which 9 079（90.9%）were gram-negative bacteria and 914（9.1%）were gram-positive bacteria. From 2017 to 2022，among all gram-negative isolates，the top three most frequently isolated pathogens were Klebsiella pneumonia，followed by Pseudomonas aeruginosa and Acinetobacter baumannii. The overall resistance rates to carbapenems in Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumonia，and Escherichia coli were 43.7%（495/1 133），19.4%（276/1 423），8.4%（279/3 304），3.6%（19/521），respectively. The overall detection rates of ceftriaxone/ciprofloxacin-resistant Klebsiella pneumonia（CTX/CRO-R-KPN），or Escherichia coli（CTX/CRO-R-ECO），and quinolone-resistant Escherichia coli（QNR-ECO）were 19.5%（644/3 304），57.6%（300/521），77.4%（403/521），respectively. The difference in resistance rates between imipenem-resistant and imipenem-susceptible Klebsiella pneumoniae was statistically significant（ P<0.05）. Except for CTX/CRO-R-ECO（ χ2=7.9 ，P>0.05），significant differences were observed in the detection rates of other major drug-resistant gram-negative bacteria in hospital（ P<0.05）. The detection of some drug-resistant strains showed an upward trend in recent years. Carbapenem-resistant Acinetobacter baumannii， Pseudomonas aeruginosa，and Escherichia coli exhibited higher resistance rate to other antibiotics. Conclusions:The detection rates of major drug-resistant gram-negative bacteria have increased in the past two years. Carbapenem-resistant strains exhibit relatively high resistance rate to cephalosporin and quinolone antibiotics. Although carbapenem antibiotics remain effective against Enterobacteriaceae，strengthened antimicrobial resistance monitoring and control of multidrug-resistant bacteria spread are necessary.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

Objective To evaluate the clinical outcome of neurosurgical robot-assisted stereotactic puncture and drainage for brain abscess.Methods A retrospective analysis was conducted on the clinical data of 53 patients with brain abscess admitted to our hospital from January 2018 to December 2024.Among them,29 cases underwent craniotomy for abscess resection(craniotomy group),while 24 cases received neurosurgical robot-assisted stereotactic puncture and drainage(robot-assisted group).The operation time,intraoperative blood loss,decompressive craniectomy rate,proportion of postoperative antibiotic regimen adjustment,postoperative hospital stay,incidence of postoperative complications,mortality rate and Glasgow outcome scale(GOS)scores 6 months after surgery of patients were compared between the two groups.Results Compared with the craniotomy group,the robot-assisted group demonstrated significantly shorter operation time,less intraoperative blood loss,and lower incidence of postoperative complication,the differences were all statistically significant(P<0.05).However,there were no statistically significant differences in terms of decompressive craniectomy rate,postoperative hospital stay,mortality rate,GOS score,or proportion of the postoperative antibiotic regimen adjustment between the two groups(P>0.05).Conclusion As a precise and minimally invasive surgical method,neurosurgical robot-assisted stereotactic puncture and drainage for patients with brain abscess can effectively improve the operational efficiency,shorten the operation time,reduce intraoperative injury,and lower the risk of postoperative complications.It has high clinical application value and potential for widespread adoption.

Objective To investigate the expression of microRNA-574(miR-574)in placental tissue of pregnant women with preeclampsia(PE)and its significance in the pathogenesis of preeclampsia.Methods The placental tissue samples of 35 PE pregnant women(the PE group)and 20 normal pregnant women(the normal group)admitted to the Department of Obstetrics in Chengde Maternal and Child Health Care Hospital from March 2021 to June 2023 were collected,and the expression of miR-574 in the different placental tissues was detected by qRT-PCR.The trophoblast cells HTR8/Svneo were cultured in vitro and divided into the overexpression group,inhibition group and control group,which were transfected with miR-574 mimics,miR-574 inhibitor and miR-NC,respectively.The cell proliferation ability of each group was detected by CCK-8 assay;The cell apoptosis rate of each group was detected by flow cytometry;The cell invasion ability of each group was detected by transwell chamber experiment;The expression of EMT related proteins of cells in each group was detected by western blot.Results Compared with the normal group,the miR-574 expression of placental tissue in the PE group was significantly increased(P<0.05),and the expression of miR-574 in pregnant women with severe PE was significantly higher than that in pregnant women with mild PE(P<0.05).Compared with the control group,the expression of miR-574 of cells increased(P<0.05),the cell proliferation ability decreased(P<0.05),the cell apoptosis rate increased(P<0.05),the number of invasive cells reduced(P<0.05),the expression of E-cadherin protein increased(P<0.05),and the expression of MMP9 and N-cadherin proteins decreased in the overexpression group(P<0.05).Compared with the control group,the expression of miR-574 of cells decreased(P<0.05),the cell proliferation ability increased(P<0.05),the cell apoptosis rate reduced(P<0.05),the number of invasive cells increased(P<0.05),the expression of E-cadherin protein decreased(P<0.05),and the expression of MMP9 and N-cadherin proteins increased in the inhibition group(P<0.05).Conclusion The expression of miR-574 in the placental tissue of PE patients is increased,and it can participate in the pathogenesis of PE by influencing proliferation,apoptosis,invasion and EMT of trophoblast cell.