ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

Objective To compare the safety of laparoscopic pancreatoduodenectomy(LPD)and open pancreatoduodenectomy(OPD)and analyze the learning curve and safety at different stages of LPD.Methods A retrospective analysis was conducted on the clinical data of 50 LPD patients and 54 OPD patients in the Department of Hepatopancreatobiliary Surgery of Suzhou Hospital Affiliated to Nanjing Medical University from January 2020 to June 2024,and intraoperative and postoperative conditions were compared.The Cumulative Sum(CUSUM)analysis method was used to analyze the technical nodes of the LPD learning curve.Results There were no significant differences in operation time and intraoperative blood loss between the LPD group and the OPD group(P＞0.05).There was also no significant difference in the incidence rates of pancreatic fistula(grade B and C),delayed gastric emptying,postoperative bleeding,biliary fistula and intra-abdominal infection between the LPD group and the OPD group(P＞0.05).A time series plot of operation time was drawn based on the patient's operation time and surgical sequence,yielding a fitted curve.Curve analysis showed initial stage and stable stage were finished at the 17th and 24th cases.The LPD learning curve could be divided into three stages:stage Ⅰ characterized as the initial stage(cases 1 to 17),stage Ⅱ characterized as the stable stage(cases 18 to 24),and stage Ⅲ characterized as the proficient stage(cases 25 to 50).The operation time in stages Ⅱ and Ⅲ was significantly shorter than that in stage Ⅰ,and the intraoperative blood loss in stage Ⅰ was significantly higher than that in stage Ⅲ(P＜0.05).There was no significant difference in the incidence of complications among the three stages(P＞0.05).Conclusion LPD and OPD show no significant differences in indications and safety.The LPD learning curve can be divided into three stages.As the number of surgeries completed increa-ses,the operation time of physicians gradually shortens,and the incidence of complications of patients gradually decreases.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective Based on the assumption of spatial heterogeneity,the distribution pattern and risk characteristics of health poverty in middle-aged and elderly people with chronic diseases are described from the perspective of spatial differentiation.In order to providing a theoretical basis for the optimization of subsequent poverty reduction policies and a model policy for other countries.Methods It used factor detector and interaction detector to capture the role of single-factor and multi-factor interactions on the spatial differentiation of health poverty,and risk detectors were utilized to explore the high-risk factors in risky areas Results The single factor explanation of medical assistance and health education activities is prominent,and the factors such as PM2.5,old-age dependency ratio and urban unemployment rate have strong interaction.Furthermore,it identified high-risk factor characteristics in areas at high risk of health poverty.Conclusion The spatial differentiation pattern of health poverty among the middle-aged and elderly chronic disease population in China is the result of the synergistic driving effect of multidimensional factors,and there is variability in the risk characteristics among regions.The government should establish a contextual optimization strategy and pay attention to the joint effect of multiple factors to establish a synergistic management system.

Objective To investigate the value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)for predicting high-risk coronary plaques in elderly males.Methods A retrospective study was conducted on 46 elderly males aged ≥60 years undergoing health check-ups and coro-nary computed tomography angiography in our hospital between May and July 2024.Their general clinical data were collected.Artificial intelligence software was used to analyze coronary calcium scores and plaque characteristics.The participants were divided into a high-risk plaque group(n=15)and a non-high-risk plaque group(n=31).The differences were compared between the two groups.Multivariate logistic regression analysis was used to identify the influencing factors for high-risk coronary plaques.ROC curve was plotted to determine the predictive value of serum Lp-PLA2 for high-risk plaques,and its AUC value was calculated.Results The high-risk plaque group had significantly larger proportions of smoking history and hyperlipidemia,and higher level of homocysteine and Lp-PLA2 than the non-high-risk plaque group(P＜0.05,P＜0.01).Multiva-riate logistic regression analysis indicated that Lp-PLA2 was an independent risk factor for high-risk coronary plaques(HR=1.030,95％CI:1.008-1.053,P＜0.05).ROC curve analysis revealed that the AUC value of Lp-PLA2 in predicting high-risk coronary plaques was 0.833(95％CI:0.694-0.927,P＜0.01),with a sensitivity of 93.3％,a specificity of 71.0％,a positive predictive value of 62.5％,and a negative predictive value of 100％.Conclusion Serum Lp-PLA2 is of signif-icant value in predicting high-risk coronary plaques in elderly men.

Objective To predict the risk of coronary atherosclerosis using cerebral small vessel disease and cerebral artery stenosis in order to assist early identification of coronary artery disease(CHD).Methods A retrospective analysis was conducted on 130 patients(aged≥65 years)who underwent cerebral MRI,magnetic resonance angiography(MRA),and coronary computed tomo-graphy angiography in the Chinese PLA General Hospital between January 2019 and December 2024.Based on coronary computed tomography angiography results,the patients were categorized into an asymptomatic CHD group(56 cases)and a non-CHD group(74 cases).Cerebral MRI and MRA were used to assess white matter hyperintensity,enlarged perivascular spaces,lacunar infarcts,cerebral microbleeds(CMB)scores,total score of cerebral small vessel disease and degree of cerebral artery stenosis.Multivariate logistic regression analysis was employed to identify the clinical and radiological indicators related to CHD.Then a predictive model was constructed,and then its performance in early predicting CHD was evaluated.Results Blood glucose,low-density lipoprotein cholesterol,CMB score≥ 1,and≥50％stenosis of the posterior cerebral artery were independent risk factors for CHD(P＜0.05).The combined predictive model integrating clinical indicators,cerebral small vessel disease,and cerebral artery stenosis demonstrated the best performance,with an AUC value of 0.867(95％CI:0.807-0.927),outperforming the clinical model and the clinical-cerebral small vessel disease model.Conclusion cerebral small vessel dis-ease and cerebral artery stenosis are closely related to coronary atherosclerosis.The predictive model integrating clinical features and cerebrovascular disease imaging markers provides impor-tant reference for early screening of CHD.

Objective:To analyze the epidemiological characteristics of drug resistance genes of carbapenemase-producing Escherichia coli (CPECO) in Henan Province Hospital of Traditional Chinese Medicine from 2021 to 2023, providing data support and theoretical basis for controlling nosocomial infections of CPECO.Methods:Using a cross-sectional study, 30 carbapenem-resistant Escherichia coli (CRECO) strains confirmed by VITEK-2 Compact identification and drug sensitivity test in the Clinical Microbiology Laboratory of Henan Province Hospital of Traditional Chinese Medicine from 2021 to 2023 were tested, using carbapenemase inhibitor enhancement test to conduct preliminary screening of carbapenemases, and colloidal gold immunochromatography and polymerase chain reaction (PCR) were used to determine the phenotypes and genotypes of common carbapenemases ( blaKPC, blaNDM, blaVIM, blaIMP, blaOXA) respectively, and the genotypes ( blaSHV, blaTEM, blaCTX) of common extended Spectrum beta-lactamases (ESBL) were confirmed using PCR. The PCR amplification products of carbapenemase and ESBL positive strains were Sanger-sequenced, and the sequencing products were compared on the Blast website to determine the exact carbapenemase and ESBL genotypes. Sequence typing (ST) was performed on CPECO using the Achtman multi-locus sequence typing scheme to determine the cloning relationship between different strains. Results:A total of 21 CPECO strains were screened. Drug sensitivity test results showed that CPECO strains showed widespread drug resistance, with the resistance rate to monocyclic (aztreonam) and trimethoprim/sulfamethoxazole being over 60%(16/21, 14/21), and the resistance rate to other antibacterial drugs being 100%. Only the sensitivity to aminoglycosides and fosfomycin remained relatively high, and no strains resistant to tigecycline and colistin were found. Colloidal gold immunochromatography detected 18 blaNDM types, 2 blaKPC types, and 1 blaIMP type. Sequencing of drug resistance gene PCR products classified 17 blaNDM-5 strains, 1 blaNDM-4 strain, 2 blaKPC-2 strain, and 1 blaIMP-4 strain, which were completely consistent with the results of screening test and colloidal gold immunochromatography. ESBL resistance gene testing showed that the detection rate of blaTEM was 42.9%(9/21), blaCTX-M was 33.3%(7/21), and blaSHV was 4.8%(1/21). The rate of blaNDM producing CPECO carrying both ESBL resistance genes was 27.8%(5/18). The MLST typing results revealed 11 sequence types (STs), including one ST155 clonal complex and nine singleton STs. Among these, there were seven strains of ST167, five strains of ST410, and one strain each of ST58, ST68, ST69, ST93, ST131, ST155, ST648, ST1114, and ST3268. Conclusion:The main resistance mechanism identified in this study for CPECO was the production of blaNDM-5 carbapenemase, with a high proportion of strains also carrying blaTEM-1D and/or blaCTX-M-15 ESBLs. MLST typing found that the epidemic strain of CPECO showed certain polymorphism, but there were clonal transmission of multiple clonal complexes between ST167 and ST410.