Immune inflammatory response runs through the whole pathological process of liver injury， but its specific regulatory mechanism remains unclear. Recent studies have shown that the Notch signaling pathway plays an important role in liver injury by regulating macrophage polarization， activating neutrophil recruitment， and modulating the differentiation of regulatory immune cells. This article systematically reviews the molecular mechanisms of the Notch signaling pathway in mediating immune inflammatory response in liver injury， in order to provide new perspectives for clarifying the molecular mechanism of immune inflammatory damage in liver diseases， as well as a new reference for future research directions.

Objective To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. Methods Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO₂ mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. Results A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). Conclusions The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.

Objective:There are a variety of minimally invasive interventional treatments for trigeminal neuralgia,and the efficacy evaluation is different.The preferred treatment scheme is still controversial.This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia(PTN)treated with percutaneous balloon compression(PBC)for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation(RT)who then received PBC for PTN,and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. Methods:We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021,including 49 patients who received PBC for the first time(PBC group)and 54 patients who received PBC for pain recurrence after RT(RT+PBC group).General information,preoperative pain score,intraoperative oval foramen morphology,oval foramen area,balloon volume,duration of compression,and postoperative pain scores and pain recurrence at each time point on day 1(T1),day 7(T2),day 14(T3),1 month(T4),3 months(T5),and 1 year(T6)were collected and recorded for both groups.The differences in treatment effect,complications and recurrence between the 2 groups were compared,and the related influencing factors were analyzed. Results:The differences of general information,preoperative pain scores,foramen ovale morphology,foramen ovale area,T1 to T3 pain scores between the 2 groups were not statistically different(all P>0.05).The balloon filling volume in the PBC group was smaller than that in the RT+PBC group,the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group(all P<0.05).Pain recurrence was positively correlated with pain scores of T2 to T6(r=0.306,0.482,0.831,0.876,0.887,respectively;all P<0.01). Conclusion:The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

ObjectiveTo provide scientific support for the compilation of high-quality anti-nuclear， biological， and chemical （NBC） medical textbooks in China by retrieving books in the field of biological weapons defense in China， summarizing the publication time and distribution of publishing institutions， and categorizing content and key points of related books. MethodsRelevant subject terms in the field of biological weapons defense were searched through the official website of China National Digital Library and other websites， up until December 31， 2023， and were limited to books. Topic analysis was conducted on the introductions and contents of the books using the latent Dirichlet allocation （LDA） model. The number of topics was determined based on perplexity， and topics were identified according to the intertopic distance map， followed by a qualitative description of the core content of each topic. ResultsA total of 104 books were included in this study， among which four were identified as higher educational textbooks. The volume of publications increased during the periods 2002‒2004 and 2020‒2023. Research institutions accounted for the highest percentage of publishers （37.78%）， and 56.67% of the publishers were military institutions. The study identified six topics： "distribution， defense， and response to biological weapons"， "category， diagnosis， and treatment of biological warfare agents"， "response to biological public health emergencies"， "status of nuclear， biological， and chemical weapons internationally"， "biosafety risk management and prevention and control"， and "technologies and equipment related to biological hazard identification". ConclusionThere are few books in the field of biological weapons defense in China and the content is relatively outdated. In the future， the preparation of teaching materials should be aimed at practical emergency handling techniques for biological weapons， enhance the emphasis on biological weapons detection and biological warfare early warning， improve the fundamental theories at different training levels， and timely update the current research status in the field.

OBJECTIVE: This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase (DGC) in Vibrio cholerae and how its transcription is regulated by Fur and HapR. METHODS: The roles of VCA0560 was investigated by utilizing various phenotypic assays, including colony morphological characterization, crystal violet staining, Cyclic di-GMP (c-di-GMP) quantification, and swimming motility assay. The regulation of the VCA0560 gene by Fur and HapR was analyzed by luminescence assay, electrophoretic mobility shift assay, and DNase I footprinting. RESULTS: VCA0560 gene mutation did not affect biofilm formation, motility, and c-di-GMP synthesis in V. cholerae, and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity. The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator HapR. CONCLUSION Overexpressed VCA0560 functions as an active DGC in V. cholerae, and its transcription is repressed by Fur and HapR.
Vibrio cholerae/genetics* ; Biofilms ; Quorum Sensing ; Mutation ; Gene Expression Regulation, Bacterial ; Bacterial Proteins/genetics*

Purpose To assess the feasibility of nuclear score combined with ultrasound features on indeterminate thyroid nodules in fine needle aspiration cytological diagnosis.Methods A consecutive cohort of 119 thyroid fine-needle aspiration(FNA)specimens with indeterminate diagnosis(TBSRTC cate-gory Ⅲ-Ⅴ)and available histopathologic follow-up was evalua-ted.Original sonographic images and cytological slides of each nodule were reviewed by two experienced sonographers and two experienced cytopathologists respectively,and evaluated jointly to obtain consensus.The identification of the optimal cut-off points of simplified nuclear score and ultrasound features score for the diagnosis of malignancy or low-risk neoplasm were evalu-ated using the receiver operating characteristic(ROC)curves and the assessment of the area under the ROC curve(AUC).The specificity,sensitivity,positive predictive value(PPV)and negative predictive value(NPV)of nuclear score and US score were evaluated from crosstabs based on Cut-off points and signif-icance were calculated.The diagnostic accuracy of simplified nuclear score combined with ultrasound features was estimated by Logistic regression and ROC curve analysis.Results Nucle-ar grooves,intra-nuclear inclusions and chromatin clearing were more common in malignancy/low-risk neoplasms(P = 0.001,0.013 and 0.001 respectively).A Cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm,and the sensitivity was 99.1%.Nodule height greater than width,absent halo sign,irregular margin and absent intranodular vascularization were more common in malig-nancy/low-risk neoplasms(P = 0.003,0.007,0.003 and 0.004 respectively).When the Cut-off point was set as≥5,the PPV and specificity for defining malignancy/low-risk neoplasm were 95.9%and 78.6%respectively.ROC curve analysis showed that the diagnostic accuracy of nuclear score combined with US score(0.873,95%CI = 0.777-0.970)was higher than that of nuclear score alone(0.817,95%CI = 0.687-0.948,P =0.092)or US score alone(0.758,95%CI 0.637-0.879,P =0.047).But no significant difference was detec-ted between the combined score and the nuclear score.Conclu-sion The addition of simplified nuclear score and US score to FNA cytology can increase the diagnostic accuracy of cytology in indeterminate categories.

Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.