ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

ObjectiveTo explore the mechanism through which Banxia Baizhu Tianmatang ameliorates cognitive impairment in epileptic rats induced by lithium chloride-pilocarpine by regulating the neuroinflammatory reaction mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes. MethodsSixty male SD rats were randomly allocated into blank， model， carbamazepine （0.125 g·kg^-1·d^-1）， Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1）， and carbamazepine （0.125 g·kg^-1·d^-1） + Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1） groups （n=12）. After the modeling of epilepsy， rats were administrated with corresponding agents by gavage for 12 weeks. At the 6th and 12th week of the intervention， the rats’ hyper-excited behavior was evaluated by the stylus experiment， and at the 12^th week of intervention， the cognitive function was evaluated by Barnes maze. At the same time， the seizure frequency and severity grade （Racine score） were recorded. The serum and hippocampus tissue samples were collected after anesthesia for the following tests. Nissl staining was used to evaluate the degree of neuronal damage in the hippocampal CA1 area. The content of malondialdehyde （MDA） in the hippocampus was determined by the thiobarbituric acid （TBA） method. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical method was adopted to detect the expression of apoptosis-associated speck-like protein containing a card （ASC） in the hippocampus. Western blot was employed to quantitatively analyze the protein levels of NLRP3， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， and brain-derived neurotrophic factor （BDNF） in the hippocampus. ResultsThe model group showed increased stylus scores at the 6th and 12^th week after modeling， a decreased Barnes maze strategy score at the 12^th week， a prolonged incubation period （P<0.05）， elevated serum levels of inflammatory factors （P<0.05）， decreased neurons with scattered arrangement and large gaps in the hippocampus， increased content of MDA in the hippocampus （P<0.05）， an increased positive expression of ASC， and up-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05）. Compared with the model group， the intervention with Banxia Baizhu Tianmatang for 12 weeks was accompanied by a decreased stylus score， epileptic seizures with a decreased score， a decreased number， and shortened duration， an increased Barnes maze strategy score， shortened escape latency （P<0.01）， declined serum levels of inflammatory factors （P<0.05）， regular morphology of hippocampal neurons， reduced MDA content in the hippocampus （P<0.05）， a decreased positive expression of ASC， and down-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05， P<0.01）. In addition， compared with the carbamazepine group， Banxia Baizhu Tianmatang + carbamazepine showed improved performance in controlling the seizure， improved the cognitive behavior score and morphology of hippocampal neurons， alleviated the oxidative stress products， lowered the levels of inflammatory factors， reduced the positive expression of ASC in the hippocampus， and down-regulated the expression of Caspase-1， NLRP3 and BDNF， with no significant differences. ConclusionBanxia Baizhu Tianmatang may reduce neuroinflammation， control epileptic seizures， and ameliorate cognitive impairment by inhibiting the expression of NLRP3 inflammasomes.

Objective To analyze the technical essentials of single-microport assisted micro-uni-port thoracoscopic surgery, and to investigate its surgical efficacy and promotional value. Methods Clinical data of patients who consecutively underwent radical upper lobectomy in the Department of Thoracic Surgery of Xi'an International Medical Center Hospital from March 2023 to June 2024 were retrospectively analyzed. According to the surgical approach, patients were divided into two groups: the single-microport assisted group (underwent upper lobectomy via single-microport assisted micro-uni-port thoracoscopy) and the traditional uniportal group (underwent traditional uniportal thoracoscopic lobectomy). Clinical outcomes were compared between the two groups. Results A total of 62 patients were enrolled. There were 30 patients in the single-microport assisted group, with a mean age of (57.4±10.8) years, and 32 patients in the traditional uniportal thoracoscopic group, with a mean age of (57.6±8.7) years. The baseline data were comparable between the two groups. All patients in both groups successfully underwent minimally invasive surgery without conversion to thoracotomy. The operative time in the single-microport assisted group was significantly shorter than that in the traditional uniportal group [(146.03±30.79) min vs. (171.41±36.41) min, P=0.004]. However, there were no statistically significant differences between the two groups in intraoperative blood loss, number of dissected lymph nodes, duration of chest tube drainage, postoperative pain score, postoperative hospital stay, hospitalization cost, or incidence of postoperative complications (all P>0.05). Conclusion Single-microport assisted micro-uni-port thoracoscopic surgery for upper lobectomy can maximally integrate the advantages of three-port and uni-port VATS while effectively avoiding their disadvantages. It significantly shortens the operative time without increasing postoperative pain or complications, and represents a more minimally invasive, safer, and more convenient surgical approach.

Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

Kidney stones are a disease with high incidence, high recurrence rate and heavy economic burden. Current clinical treatments clear formed stones but fail to target the pathophysiological core of recurrence. Beyond systemic risk factors like obesity and diabetes, diet-driven gut dysbiosis is a key potential mediator of stone recurrence. Moreover, the gut-kidney syndrome and gut-kidney axis theories reveal the bidirectional regulation between intestine and kidney, among these, the gut microbiota-metabolite axis as the core functional carrier of the gut-kidney axis has a regulatory mechanism key to resolving recurrence. Currently, 16S rRNA sequencing and metagenomic sequencing have identified gut microbiota differences between stone and non-stone groups: kidney stone patients show reduced alpha diversity, imbalanced Firmicutes/ Bacteroidetes ratio, significantly higher abundance of harmful bacteria (e.g., Escherichia- Shigella), and lower abundance of oxalate-degrading bacteria ( Oxalobacter formigenes, Lactobacillus) and short-chain fatty acid (SCFA)-producing bacteria ( Faecalibacterium). Notably, gut dysbiosis persists even after surgery.Meanwhile, targeted and non-targeted metabolomics show significant abnormalities in intestinal and urinary metabolites (e.g., SCFA tryptophan derivatives) in stone patients, along with downregulated pathways including purine metabolism, caffeine metabolism and aromatic amino acid metabolism. These abnormalities promote stone formation by disrupting the intestinal barrier, worsening renal inflammation and triggering renal oxidative stress. This article reviews the aforementioned gut microbiota, metabolites and related regulatory pathways with significant inter-group differences. Combined with advances in genomics and metabolomics, it aims to provide theoretical references for further clarifying the mechanism of gut microbiota-metabolite axis regulates kidney stone formation and recurrence, and for developing microecological interventions.

Objective To explore the application value of CT classification of lumbar spinal stenosis(LSS)in selecting endoscopic decompression surgery approach.Methods The clinical data and CT imaging materials of 300 patients with LSS,who received percutaneous endoscopic decompression surgery from March 2018 to December 2024 were selected from Hengshui Municipal People's Hospital in Hebei(Halison International Peace Hospital),were retrospectively analyzed.Preoperative CT scan was performed in all patients.Taking endoscopic classification as the golden standard,the consistency between CT classification results and endoscopic classification results was assessed by Kappa consistency analysis.The effect of surgery of different approaches for percutaneous endoscopic decompression surgery was compared.Results CT diagnostic classification of type Ⅰ LSS was obtained in 87 patients(among them 3 patients with type Ⅲ LSS were misdiagnosed as type Ⅰ LSS),type Ⅱ LSS in 141 patients and type ⅢLSS in 72 patients,the total diagnostic accuracy rate was 97.67％.Using endoscopic classification as the gold standard,the Kappa values for CT diagnosis of type Ⅰ,type Ⅱ and type Ⅲ were 0.975,1.000 and 0.973,respectively.According to the CT classification results,all 300 patients successfully selected different surgical approaches to complete the surgery,and their clinical symptoms were significantly relieved without significant complications.After surgery,the Oswestry disability index(ODI)and visual analogue scale(VAS)scores of leg/lower back in patients with different LSS types showed a decreasing trend(P＜0.05).After treatment,the total frequency of taking non-steroidal drugs was significantly lower than that before surgery(P＜0.05).Conclusion The classification of LSS is highly consistent between CT scan and endoscopic examination,which is of great value for the selection of percutaneous endoscopic decompression surgery approach.

Objective:To investigate the application and clinical efficacy of customized, 3D-printed femoral bone marrow stems in the revision of tumor prostheses.Methods:A retrospective analysis was performed for the data of 11 patients (7 males and 4 females) aged 53.1±11.7 years (range, 38-75 years), who underwent 3D-printed customized revision of femoral intramedullary stems due to loosening of femoral tumor prostheses at the 960th Hospital of the Joint Support Force of the PLA from June 2021 to June 2023. The pathological types of tumors associated with the initial surgeries included 4 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 1 case of chondrosarcoma, and 1 case of plasma cell tumor. The tumor was located at the distal femur in 8 cases and the proximal femur in 3 cases. The procedures included 3 initial revisions, 7 secondary revisions, and 1 tertiary revision. The average limb shortening measured 4.6±2.2 cm (range, 2.5-9.0 cm). Prior to revision, all prostheses were fixed with bone cement, revealing enlargement of the femoral medullary cavity and cortical bone thinning. Among them, 5 cases had intramedullary stems permeabilizing the femoral cortex, and 1 case had femoral cleavage fractures. All 11 patients received personalized data for the design and 3D printing of femoral bone marrow stems.Results:The lengths and diameters of the 3D-printed porous femoral bone marrow stems ranged from 80 to 160 mm and 20 to 22 mm, respectively. Ten patients were fitted with cylindrical intramedullary handles, while one received a conical intramedullary handle. A successful revision with the 3D-printed stems was achieved in 10 patients; however, 1 case failed to accommodate the conical handle and was instead revised with a bone cement prosthesis. During the implantation of the intramedullary stems, three patients experienced minor cortical splitting, which was managed with bundling and fixation during the procedure. Immediate stability was attained for all prostheses during surgery, yet postoperative limb shortening did not undergo significant correction. All patients exhibited normal healing of their postoperative incisions. The visual analog scale for limb pain decreased significantly from 8.0±0.8 points before surgery to 1.0±0.4 points three months postoperatively ( t=25.957, P<0.001). By six months after the surgery, none of the patients reported any limb pain. Follow-up data for all 11 patients indicated an average follow-up duration of 25.2±7.5 months (range, 16-36 months), during which limb function improved satisfactorily. The Musculoskeletal Tumor Society (MSTS) score increased from 7.9±1.4 points preoperatively to 20.9±2.7 points at the last follow-up, with this change also being statistically significant ( t=14.229, P<0.001). Imaging evaluations revealed normal lower limb force lines, no rotation or longitudinal displacement of the prosthetic stem, and successful integration with the femur. Conclusion:Personalized intramedullary stems produced through 3D printing demonstrate significant clinical effectiveness in femoral tumor prosthesis revision surgery, making them a viable option for such procedures.

Objective:To investigate the mosquito-borne viruses carried by mosquito specimens collected from Huachuan county and Huanan county in Heilongjiang province.Methods:Mosquito samples were collected locally in 2023 and processed in the laboratory. Homogenates of the mosquitoes were inoculated into cells for virus isolation, followed by molecular and bioinformatics analyses of the viral isolates.Results:In 2023, ten viral isolates were obtained from Anopheles sinensis specimens collected in Heilongjiang province, China. Among these isolates, one was identified as Culex flavivirus (CxFV), one as Menghai rhabdovirus (MRV), and eight as Nam Dinh virus (NDiV). The phylogenetic analysis showed that CxFV belongs to genotype I and is clustered with the strains isolated from Liaoning province in 2011 and Ningxia Hui autonomous Region in 2019 in the same evolutionary branch, with amino acid similarity ranging from 98.2% to 99.2% and nucleotide similarity ranging from 98.8% to 99.2%. The MRV strain belongs to the same evolutionary subclade as the strain detected in Guangdong, with both nucleotide and amino acid similarity of 98.0%. Eight NDiV isolates clustered with the South Korean isolates on the same evolutionary branch, forming an independent evolutionary sub-branch. The nucleotide similarity among these eight isolates ranged from 98.5% to 99.7%, while the amino acid similarity ranged from 98.1% to 99.7%. In comparison, when matched with other NDiV isolates from China, the nucleotide similarity of these eight isolates ranged from 94.1% to 97.8%, and the amino acid similarity ranged from 93.5% to 97.7%.Conclusions:This study represents the first isolation of CxFV, MRV, and NDiV in Heilongjiang province, China, and the findings provide fundamental data for the prevention and control of mosquito-borne viral diseases in this region.

Objective:To establish a method for the rapid detection of varicella-zoster virus (VZV) by recombinase-aid amplification (RAA) combined with Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system.Methods:Clinical samples of suspected herpes zoster in Shandong province and Shanghai from 2023 to 2024 were collected, nucleic acids of positive samples were extracted, RAA-specific primers and crRNA (CRISPR RNA, crRNA) were designed for the conserved region of VZV, and the fluorescence intensity generated by Cas12a non-specific cleavage of single-stranded fluorescent probes was used to screen highly sensitive crRNAs and optimize the concentrations of crRNA, Cas12a and ssDNA probes. The sensitivity and reproducibility of the RAA-CRISPR/Cas12a detection method were evaluated by using synthesized plasmids and clinical samples, and the specificity of the method was evaluated by using other viral nucleic acids. The method was used to detect clinical samples by using the method and quantitative real-time PCR (qPCR) method, and the detection rate and consistency of the two method were compared.Results:The highly sensitive crRNA-4 was screened from the four crRNAs designed, and a VZV detection method for RAA-CRISPR/CAS12a based on fluorescence intensity measurement was established, which could be detected at 37℃ in 45 min, and the sensitivity of the detection could reach 10 copies/μL, a minimum clinical sample with a Ct value of 38.980 can be detected. It has high specificity and no cross-reactivity with Adenovirus 7, Herpes simplex virus type I, Herpes simplex virus type II, Coxsackieviruses A16, Cytomegalovirus, Epstein-Barr virus, Measles virus, Mumps virus, Enterovirus 71, Japanese encephalitis virus genotype 5. It has good stability, and can be successfully detected in low, medium and high concentrations of viral positive plasmids with good consistency. The detection rate of the clinically positive samples was 100%, which was completely consistent with the qPCR test result.Conclusions:RAA isothermal amplification technology combined with CRISPR-CAS12a technology was used to establish an accurate method for the detection of VZV virus, which was highly sensitive, specific, and had low requirements for experimental conditions, and could be completed within 45 min, which could provide strong technical support for the early detection of VZV.

Objective:To compare the effects of propofol and dexmedetomidine for sedation on the outcome in mechanically ventilated patients with severe pulmonary infection.Methods:Patients with severe pulmonary infection (Clinical Pulmonary Infection Score >7) requiring mechanical ventilation from the Medical Information Mart for Intensive Care Ⅳ database between 2008 and 2020 were selected and divided into propofol group and dexmedetomidine group based on the sedative agent used. The primary outcome was all-cause in-hospital mortality, and secondary outcomes included 90-day all-cause mortality and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders, and logistic regression and linear regression were applied to analyze the effects of the two sedative drugs on the outcomes of mechanically ventilated patients with pulmonary infection. Kaplan-Meier survival curves were used to analyze survival outcomes.Results:A total of 6 204 critically ill patients with pulmonary infection requiring mechanical ventilation were included, with 3 439 cases in propofol group and 2 765 cases in dexmedetomidine group. The baseline characteristics between the two groups were well balanced (standardized mean difference < 0.1) after IPTW adjustment. In the IPTW-adjusted cohort, the in-hospital all-cause mortality and 90-day all-cause mortality were significantly lower in dexmedetomidine group than in propofol group (439.2[18.7%] vs 563.6[24.1%], 618.0[26.3%] vs 733.6[31.3%], P<0.001), the results of Further Kaplan-Meier survival curve analysis showed that the 90-day all-cause mortality was significantly lower in dexmedetomidine group than in propofol group ( P<0.01). Conclusions:Compared with propofol, dexmedetomidine can decrease the mortality rate and improve the prognosis in mechanically ventilated patients with severe pulmonary infection when used for sedation.