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.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective To explore the effects and mechanism of Baitouweng Decoction in intestinal mucosal healing in mice with ulcerative colitis(UC)based on RIPK1/RIPK3/MLKL signaling pathway.Methods Totally 30 C57BL/6 male mice were randomly divided into control group,model group,Baitouweng Decoction group,infliximab group and combination group(Baitouweng Decoction+infliximab),with 6 mice in each group.A mouse model of UC was established by free administration of 3.5%sodium gluconate sulfate solution for 7 days.After modeling,Baitouweng Decoction group was given 8 g/kg Baitouweng Decoction solution by gavage daily,while the infliximab group was given 5 mg/kg infliximab intraperitoneal injection,the combination group was given synchronous gastric and intraperitoneal injection,while the control group and model group were given equal volume of normal saline by gavage for 7 consecutive days.The body mass of mice was recorded daily,fecal characteristics were observed,and disease activity index(DAI)score was performed,colon length was measured after intervention,ELISA was used to detect the contents of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),RT-qPCR was used to detect mRNA expressions of RIPK1,RIPK3 and MLKL in colon tissue,Western blot and immunofluorescence staining were used to detect the expressions of RIPK1,RIPK3 and MLKL protein in colon tissue.Results Compared with the control group,the model group mice showed a decrease in body mass(P<0.01),an increase in DAI score(P<0.01),a shortened colon length(P<0.01),and an increase in serum IL-6 and TNF-α content(P<0.01);colonic mucosal was destructed,with disappearance of crypts and glandular structures,extensive infiltration of inflammatory cells,and increased pathological score of colon tissue(P<0.01);the mRNA and protein expressions of RIPK1,RIPK3 and MLKL in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the body mass of mice in each treatment group increased(P<0.01),and the DAI score decreased(P<0.01),colon length increased(P<0.01),and the contents of serum IL-6 and TNF-α decreased(P<0.05,P<0.01);the destruction of the colonic mucosal barrier was reduced,the pathological score of colon tissue was reduced(P<0.05);the expressions of RIPK1,RIPK3 and MLKL mRNA and protein in colon tissue decreased(P<0.05,P<0.01).Conclusion Baitouweng Decoction can alleviate intestinal mucosal damage and inflammation in UC mice,and its mechanism may be related to the inhibition of the RIPK1/RIPK3/MLKL signaling pathway.

Objective:To investigate whether intestinal rehabilitation therapy (IRT)could optimize the effectiveness of IRT in patients with short bowel syndrome (SBS) caused by acute mesenteric ischemia (AMI) with chronic multivessel lesions.Methods:Clinical data of 18 hospitalized patients diagnosed with AMI leading to SBS and undergoing IRT at the Eastern Theater General Hospital of the People's Liberation Army from Jan 2012 to Oct 2023 was retrospectively analyzed.Result:Following IRT, the revascularization group showed significantly greater increases in ASMI and grip strength compared to the control group [(0.28±0.26) kg/m 2vs. (0.02±0.21) kg/m 2, P=0.033, and (0.97±0.33) kg vs. (0.48±0.34) kg, P=0.007, respectively]. Similarly, the increase in EN intake was significantly higher in the revascularization group compared to the control group [(572.5±93.6) ml/d vs. (375.2±176.3) ml/d, P=0.012], accompanied by a greater improvement in intestinal nitrogen absorption rate [(25.06±14.06)% vs. (13.84±4.62)%, P=0.034] and a more substantial decrease in GSRS scores [(-15.88±3.94) vs. (-6.33±5.13), P=0.030]. Moreover, there were significant differences in the composition of EN formulations between the two groups after IRT ( P=0.046). Additionally, SF-36 scores at discharge were significantly higher in the revascularization group than that in the control group for five indicators including BP, GH, VT, SF, and MH ( P<0.05). Conclusions:For patients with SBS resulting from AMI by chronic multivessel lesions, revascularization therapy may not leading to higher growth in weight and hematological nutritional indicators during IRT, but it is beneficial for improving muscle function, improving EN absorption, increasing the likelihood of PN independence, relieving gastrointestinal symptoms, and enhancing overall quality of life.

Shufeng Jiedu capsules， a Chinese patent medicine composed of Polygoni Cuspidati Rhizoma et Radix， Forsythiae Fructus， etc.， has shown positive effects in the clinical treatment of upper respiratory tract infections， pharyngitis， acute exacerbation of chronic obstructive pulmonary disease （AECOPD）， and coronavirus disease 2019 （COVID-19）. The available evidence suggests that Shufeng Jiedu capsules can modulate the proportions of immune cells and the concentrations of inflammatory cytokines， thereby easing symptoms and enhancing cure rates. The existing reviews predominantly focus on the clinical applications of Shufeng Jiedu capsules， while the comprehensive review of the immunomodulatory effect of this medicine remains to be carried out. This review delineates the immune responses triggered by respiratory tract infections， and then summarizes the clinical application of Shufeng Jiedu capsules and its main chemical components. Principally， this review summarizes the immunomodulatory and anti-inflammatory mechanisms， mainly focusing on various immune cells including macrophages， neutrophils， natural killer （NK） cells， and lymphocytes. In addition， this paper discusses the influences of Shufeng Jiedu capsules and its main chemical components on signaling pathways， secretion of pro-inflammatory cytokines， and antibody production. In terms of innate immunity， the intervention effects of Shufeng Jiedu capsules are highlighted by its capacity to inhibit the activation of nuclear factor kappa-B （NF-κB） and interferon regulatory factor 3 （IRF3） pathways. Additionally， Shufeng Jiedu capsules have been shown to reduce the expression of microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）， thereby suppressing the inflammation and autophagy of macrophages. Furthermore， the influence of this medicine extends to altering the proportions of neutrophils and nature killer（NK） cells. Regarding adaptive immunity， Shufeng Jiedu capsules can increase the proportion of T cells in peripheral blood and restore the balance of B cells. This review aims to provide directions for the further research and clinical application of Shufeng Jiedu capsules.

Objective:To identify the factors associated with the care needs of the older adults aged 65-105 by age groups,and to compare these factors across different age groups.Methods:A total of 12 244 older adults from the Chinese longitudinal healthy longevity survey(CLHLS)conducted in 2018 were included in the analyses.The participants were categorized into three age groups:young-old(aged 65-79),middle-old(aged 80-89),and oldest-old(aged 90-105).The level of disability was measured by the disability index(DI)in four dimensions,reflecting their care needs.Potential factors associated with care needs were selected based on the health ecological model(HEM),including per-spectives of personal characteristics,behavioral characteristics,interpersonal network,living and working conditions,and policy environment.Multifactor analysis was performed using multinomial Logistic regres-sion.Results:Among China's 12 244 older adults,43.4％had medium or high care needs.Factors for higher care needs of older adults included higher age,higher number of chronic diseases,no exercise habit,excessive sleep duration(≥9 h/d),depressive tendency,living with children or spouse,and un-educated(all P＜0.05).In addition,the young-old group who were past smokers(OR=2.009,95％CI:1.019-3.959),were past drinkers(OR=2.213,95％CI:1.141-4.291),and reported self-per-ceived poverty(OR=2.051,95％CI:1.189-3.540),had higher level of care needs.The middle-old group who were female(OR=1.373,95％CI:1.038-1.817),never drank alcohol(OR=1.551,95％CI:1.059-2.269),and were lack of medical insurance(OR=1.598,95％CI:1.053-2.426),and had higher level of care needs.The oldest-old group who were female(medium care needs vs.low care needs:OR=1.412,95％CI:1.062-1.878;high care needs vs.low care needs:OR=1.506,95％CI:1.137-1.993),reported self-perceived poverty(OR=2.064,95％CI:1.282-3.323),and were lack of medical insurance(OR=1.621,95％CI:1.148-2.291),and had higher level of care needs.Conclusion:The identical factors associated with care needs across different age groups include age,chronic disease,exercise,sleep,depression,living arrangement,and education.Smoking,alcohol consumption,and economic status are specific factors among the young-old group of the older adults,while gender and medical insurance are specific factors among the middle-old and the oldest-old group of the older adults.We recommend conducting prospective cohort studies and intervention studies among specific age groups on the above factors to provide reliable evidence for policy formulation.