Objective:To establish the HPLC fingerprint of Bolbostemmatis Rhizoma standard decoction; To determine the three effective components with similar structure by quantitative analysis of multi-components by single marker (QAMS); To evaluate the quality of Bolbostemmatis Rhizoma standard decoction.Methods:HPLC was adopted to establish the fingerprints of 15 batches of Bolbostemmatis Rhizoma standard decoction. The Chromatographic column was Waters XBridge Phenyl (4.6 mm×250 mm, 5 μm). The mobile phase was acetonitrile-0.1% phosphoric acid solution with gradient elution. Cluster analysis (HCA) and principal component analysis (PCA) were conducted based on the relative peak area of common peaks. The same method as the fingerprint was used to establish QAMS of tubeimoside A, B, C on Bolbostemmatis Rhizoma standard decoction.Results:There were 14 common peaks in the fingerprint of Bolbostemmatis Rhizoma standard decoction. It was confirmed that the peak 3 was L-tryptophan, the peak 11 was tubeimoside B, the peak 12 was tubeimoside C, and the peak 13 was tubeimoside A. 15 batches of Bolbostemmatis Rhizoma standard decoction from different origins were divided into 3 categories by HCA and PCA. There was no significant difference between QAMS and the external standard method (ESM) through the system suitability inspection. Conclusion:This method is accurate, reliable and has good specificity, which can effectively evaluate the quality of Bolbostemmatis Rhizoma standard decoction.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

ObjectiveTo explore the mechanism of Taohong Siwutang in regulating the levels of inflammatory mediators， cysteine-dependent aspartate-specific protease Caspase-14， and recombinant envoplakin （EVPL） in the mouse model of psoriasis. MethodForty-eight BALB/c mice were randomized into blank， model， methotrexate tablets（3.6×10^-4 g·kg^-1）， and low-， medium-， and high-dose Taohong Siwutang groups（7.14，14.28，28.56 g·kg^-1）. The mouse model of psoriasis-like skin lesion was induced by applying 5% imiquimod cream on the back of mice， and drug intervention was carried out at the same time. The psoriasis area and severity index （PASI） was scored by photographing. Hematoxylin-eosin staining was employed to observe the pathological changes of the skin， which was evaluated based on the Baker score. The levels of interleukin （IL）-2， IL-17， IL-22， and IL-23 in the peripheral blood of mice were measured by the enzyme-linked immunosorbent assay. Immunohistochemical staining was adopted to detect the positive expression of Caspase-14 and EVPL in mouse skin lesions. Western blot and real-time polymerase chain reaction were employed to determine the protein and mRNA levels， respectively， of IL-2， IL-17， IL-22， IL-23， Caspase-14， and EVPL in mouse skin lesions. ResultCompared with the blank group， the model group showed increased PASI score and Baker score， elevated levels of IL-2， IL-17， IL-22， and IL-23 in the peripheral blood， up-regulated mRNA and protein levels of IL-2， IL-17， IL-22 and IL-23， and down-regulated mRNA and protein levels and positive expression of Caspase-14 and EVPL in skin lesions （P<0.05）. Compared with the model group， drug interventions reduced the PASI score and Baker score， lowered the levels of IL-2， IL-17， IL-22， and IL-23 in the peripheral blood， down-regulated the mRNA and protein levels of IL-2， IL-17， IL-22， and IL-23， and up-regulated the mRNA and protein levels and positive expression of Caspase-14 and EVPL in skin lesions （P<0.05）. ConclusionTaohong Siwutang demonstrates good anti-inflammatory effect and skin barrier repair function in the treatment of psoriasis. It can significantly reduce the levels of inflammatory mediators in the peripheral blood and skin lesions and promote the expression of Caspase-14 and EVPL involved in skin barrier repair in the mouse model of psoriasis.

A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.

Objective:Hypoxia is an important cause of chemotherapy resistance in gastric cancer.However,little is known about the growth of gastric cancer under purely hypoxia conditions.This study aims to study the effect of hypoxia on the growth patterns of gastric cancer cells and explore the response of gastric cancer cells to the chemotherapeutic drug 5-fluorouracil(5-FU)in a hypoxic environment. Methods:Gastric cancer cells MKN45 were cultured under 1%oxygen hypoxia and conventional air conditions.An intervention group with the addition of the chemotherapeutic drug 5-FU was also established.The proliferation and apoptosis of gastric cancer cells under different oxygen conditions and intervention groups were detected using the cell counting kit-8(CCK-8)method,JC-1 mitochondrial membrane potential assay,and Annexin-V/PI double staining method.Cell cycle changes were detected by flow cytometry,and mitochondrial changes were detected using electron microscopy. Results:In the absence of 5-FU intervention,compared with the normoxia group,the hypoxia group showed higher rates of early and late apoptosis and higher cell death rates as indicated by the JC-1 mitochondrial membrane potential assay,Annexin-V/PI double staining,and CCK-8 results.Flow cytometry results showed that the cell cycle was arrested in the G0/G1 phase without progression.Electron microscopy revealed more severe mitochondrial destruction.However,with 5-FU intervention,the hypoxia group showed lower apoptosis rates,more cell cycle progression,and less mitochondrial destruction compared with the normoxia group. Conclusion:Hypoxic environments promote apoptosis and even death in gastric cancer cells,but hypoxia counteracts the efficacy of the chemotherapeutic drug 5-FU,which may contribute to 5-FU chemotherapy resistance.

Berberine is a commonly used traditional Chinese medicine,which has the antimicrobial and anti-inflammatory properties.Ongoing investigations have identified berberine as an effective medicine for systemic diseases,such as cardiovascular diseases,diabe-tes mellitus and neurological disorders.At the same time,there exists a close relationship between oral microbiota and these systemic diseases.This review focuses on the relationship between berberine,oral microbiota and systemic diseases,offering new insights for the treatment of systemic diseases.

Objective To duplicate the existing model of intracranial oculomotor nerve injury in rats,and propose a new method of orbital cavity clamping oculomotor nerve,evaluate the respective advantages of the two models.Methods Male SD rats were used as experimental animals,and two different methods of preparing oculomotor nerve injury models were compared.Sphenopalatine foramen approach group:clamp the initial segment of the oculomotor nerve from the opening of the upper edge of the orbit for 10 s.The skull base approach group,the temporal bone was removed and the infratentorial segment of the oculomotor nerve was clampped for 10 s.Taking the success rate,survival rate and survival status of the model rats as observation indicators,the applicability of the model rats to the intervention of gastric perfusion was and intraorbital electroacupuncture evaluated.Results The success rate after molding 24 h:In the sphenopalatine foramen approach group was 92.31%(12/13);In the skull base approach group was 34.29%(12/35).Survival rate:7 d after gavage:In the sphenopalatine foramen approach group,6 patients survived,with a survival rate of 100.00%(6/6).Four patients survived in the skull base approach group,with a survival rate of 66.67%(4/6).7 days after orbital electroacupuncture:Five patients survived in the sphenopalatine foramen approach group(83.33%,5/6).Three patients survived in the skull base approach group,with a survival rate of 50.00%(3/6).Survival state of rats(0-20 points,the smaller the score,the better):24 h after modeling,the status score of sphenopalatine foramina approach group was 4.11±0.90,and that of skull base approach group was 12.39±1.378.After 7 days of intragastric administration,the score of sphenopalatine foramina approach group was 2.50±1.05,and the score of skull base approach group was 14.50±0.58.The score of sphenopalatine foramina approach group was 2.00±1.22 and the score of skull base approach group was 15.33±0.58 after 7 days of intraorbital electroacupuncture intervention.The success rate,survival rate and survival state of rats in sphenopalatine foramina approach group were better than those in skull base approach group 24 h after modeling(P<0.05);The survival rate and survival state of rats in sphenopalatine foramina approach group were better than those in skull base approach group 7 days after gavage and orbital electroacupuncture intervention(P<0.05).Conclusion The model of oculomotor nerve injury prepared by sphenopalatine foramina approach is more suitable for the basic research of nerve repair after the intervention of gastric gavage and orbital electroacupuncture.The model rats with oculomotor nerve injury prepared by the base approach are more suitable for the basic research after the injury of the intracranial segment of the oculomotor nerve.

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.

Objective To observe the value of vector flow mapping(VFM)technique for assessing changes of left ventricular diastolic function in ovarian cancer(OC)patients who underwent postoperative chemotherapy.Methods Totally 37 OC patients who received postoperative chemotherapy were prospectively enrolled in chemotherapy group,while 40 healthy adults were taken as controls(control group).Routine echocardiography and VFM were performed for chemotherapy group before chemotherapy,after 3 and 6 cycles of chemotherapy,also for controls at enrollment,and comparison was performed between groups before chemotherapy,as well as among different time points within chemotherapy group,and the correlations of VFM results with hemoglobin and routine echocardiographic results in chemotherapy group were analyzed.Results No significant difference of age,body mass,body surface area(BSA),nor hemoglobin level,routine echocardiographic and VFM results before chemotherapy was found between groups(all P＞0.05).With the process of chemotherapy,hemoglobin level gradually decreased,the isovolumic relaxation period(IR),atrial systole period(AS)intraventricular pressure difference(IVPD)and intraventricular pressure gradient(IVPG)of the left ventricle gradually increased(adjusted P＜0.05),whereas routine echocardiography only showed that the left atrial volume index(LAVI)and the ratio of early mitral inflow velocity and the mean mitral annular early diastolic velocity(E/e')increased after 6 cycles of chemotherapy compared with those pre-chemotherapy(adjusted P＜0.05).In chemotherapy group,VFM results in all diastolic subphases were strongly correlated with hemoglobin levels(|r|=0.718 to 0.836,all P＜0.05),weakly to moderately correlated with LAVI(|r|=0.375 to 0.525,all P＜0.05)and moderately correlated with E/e'(|r|=0.424 to 0.537,all P＜0.05).Conclusion The diastolic function of left ventricle was probably damaged in early stage after postoperative chemotherapy in OC patients.VFM might detect slight changes of early diastolic function of left ventricle more sensitively than routine echocardiography.