ObjectiveBased on analytic hierarchy process（AHP）-criteria importance through intercriteria correlation（CRITIC） hybrid weighting method， grey relational analysis and backpropagation artificial neural network（BP-ANN）， to optimize the water extraction process of Qizhi prescription， so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL₉（3⁴） orthogonal test was employed， and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components， including astragaloside Ⅳ， polygalaxanthone Ⅲ， calycosin-7-O-β-D-glucoside， tenuifolin， and 3，6′-disinapoylsucrose， as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times， extraction time， and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis， variance analysis， and grey relational analysis. Meanwhile， a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription， and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components（astragaloside Ⅳ， tenuifolin， calycosin-7-O-β-D-glucoside， polygalaxanthone Ⅲ， and 3，6′-disinapoylsucrose） and dry extract yield were 25.7%， 20.82%， 16.41%， 12.45%， 15.96% and 8.67%， respectively. The optimized extraction process parameters were extracted 3 times with 8， 6， 6 times the amount of water， each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results， and the mean square error（MSE） of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible， which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix， and the average comprehensive score of the validation test was 90.85 with the relative standard deviation（RSD） of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules， and the optimized extraction process can effectively improve the extraction efficiency of active ingredients， which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

Direct compression is an ideal method for tablet preparation, but it requires the powder's high functional properties. The functional properties of the powder during compression directly affect the quality of the tablet. 15 parameters such as Py, FES-8KN, FES-12KN, FES-16KN, CR-8KN, CR-12KN, and CR-16KN were used as the characteristic variables in this paper. Unsupervised learning methods like principal component analysis, cluster analysis, and factor analysis were applied to analyze and classify the compression behavior data of 36 traditional Chinese medicine powders. The results showed that both different dimensionality reduction classification methods could effectively differentiate the compression behavior characteristics of 36 traditional Chinese medicine compound powders. The hierarchical cluster analysis results showed a better agreement with the actual compression phenomena of the powders, where group 1 was high elasticity and low compressibility, group 2 was easily compressed and hard to break, group 3 was excellent compressibility and compactibility. This study is expected to provide references and ideas for predicting the behavior of traditional Chinese medicine powders and the screening of tablet formulations.

Objective To investigate the current status and serologic characteristics of occult HBV infection in the adult physical examination population in Zigong region. Methods A total of 126 381 patients who were examined in the physical examination center and gastroenterology department of The First People's Hospital of Zigong City from April 2023 to September 2024 were screened, and 21 615 eligible cases were included in the study. The current status of infection was analyzed and serological patterns and serological characteristics of the included individuals were compared. Results This study screened 126 381 patients, all of whom underwent serum HBsAg testing, and 21 615 patients (17.10%) underwent HBV DNA testing, of which 7 992 were HBV DNA positive (>102 IU/mL) and HBsAg negative, accounting for 36.97% of the total number of patients who underwent HBV DNA testing. Anti-HBc positivity was significantly higher than other serologic patterns, and the lowest rate of HBV DNA positivity was found in those who were positive for anti-HBc, anti-HBs and anti-HBe. The lowest male-to-female ratio (1.25:1) was found in patients with both anti-HBc, anti-HBs and anti-HBe positivity, which was significantly lower than that of patients with the other three serologic characteristics (P=0.005). There were no significant differences in age, BMI, AST, ALT, and TBiL levels among patients with different serum characteristics (all P>0.05). The HBV viral load is highest in patients with anti HBc combined with anti HBe positivity, while the HBV viral load is lowest in patients with anti HBc positivity, anti HBs positivity, and all anti HBe positivity (P<0.001). Viral genotypes were predominantly B-type, and there were differences in genotype distribution among the four groups of patients (P<0.001). Conclusion The level of occult HBV infection was high in the adult medical examination population in Zigong region, mostly characterized by anti-HBc positivity, with the lowest male-to-female ratio among patients who were positive for anti-HBc, anti-HBs, and anti-HBe, and the highest HBV viral load among patients who were positive for anti-HBc combined with anti-HBe.

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally.Programmed death protein-1(PD-1)/programmed death protein ligand-1(PD-L1)inhibitors promote the reactivation of anti-tumor immune response by bloc-king the negative modulatory signaling pathway of T cells'activa-tion and inhibiting the immune escape pathway of tumor cells.PD-1/PD-L1 inhibitors become a novel therapeutic strategy to treat HCC.However,long-term clinical outcomes show that HCC patients treated with anti-PD-1/PD-L1 monotherapy still have high rates of recurrence and metastasis.Combination immuno-therapy is a novel therapeutic strategy to treat advanced HCC pa-tients,among which PD-1/PD-L1 inhibitors in combination with anti-vascular endothelial growth factor(VEGF)agents have showed promising efficacy and better safety.PD-1/PD-L1 inhib-itors plus anti-VEGF agents combined therapy inhibit the growth of hepatoma cells by participating in the cancer immunity cycle pathway.This review focuses on the research progress of PD-1/PD-L1 inhibitors,anti-VEGF agents and their combined therapy in the clinical treatment of HCC.

Aim To study the main active ingredients,key targets and pathways of Cigu Xiaozhi Decoction(CXD)based on network pharmacology,and to ana-lyze and verify the mechanism of CXD on the transfor-mation of"inflammatory cancer"in non-alcoholic steatohepatitis(NASH)by animal experiments.Meth-ods The potential targets and signaling pathways of CXD in the treatment of NASH"inflammatory carcino-ma"were predicted based on network pharmacology.The mouse model of NASH was induced by methionine-choline deficiency diet(MCD),and CXD and epider-mal growth factor receptor(EGFR)inhibitors were given for 28 days.The mice were killed after the inter-vention,and the liver histopathology of each group was observed by hematoxylin-eosin method(HE).The rel-ative expression levels of EGFR,phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT)in liver tissue of mice in each group were detected by Western blot.The contents of interleukin-6(IL-6),interleu-kin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosor-bent assay(ELISA).Results A total of 284 poten-tial active components,159 potential therapeutic tar-gets and 20 key targets of CXD were identified by net-work pharmacological screening.CXD could affect multiple biological processes such as cell proliferation and inflammatory response,involving multiple signa-ling pathways such as tumor and PI3K/AKT.Animal experiments showed that CXD could reduce the levels of IL-6,IL-1β and TNF-α in serum of NASH mice.The relative expression of PI3K and AKT protein in liv-er tissue decreased,and the relative expression of EG-FR protein was increased.Conclusion CXD can reg-ulate EGFR/PI3K/AKT signaling pathway by partici-pating in biological processes such as cell proliferation and inflammatory response,and improve liver tissue injury in NASH mice.

Objective To investigate the effect of artemisinin(ART)on the malignant biological behavior of colorectal cancer(CRC)cells stimulated by glucose and its mechanism.Methods The concentration gradients of 0,5,10,20,40 and 60 μmol/L of ART were used to treat the human colorectal cancer cell line SW480,and then the cell viability was detected by CCK-8.Cell apoptosis was detected by flow cytometry.Transwell was used to detect the cell migration and invasion.Western blot was used to detect the apoptosis,epithelial-mesenchymal transition(EMT)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)related proteins expression.Results Compared with the 0 μmol/L of ART,the viability of SW480 cells decreased under 5,10,20,40,60 μmol/L of ART treatment(P<0.05),and IC50 was 36.91 μmol/L.Therefore,the cells treated with 10,20 and 40 μmol/L of ART were as the low-dose,medium-dose and high-dose ART groups,the cells treated with 0 μmol/L of ART were as the control group,and the cells treated with 40 μmol/L of ART and 10 μmol/L of Coumermycin A1 were as the Coumermycin A1 group.Compared with the control group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the low-dose ART group,the medium-dose ART group,and the high-dose ART group decreased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin increased(P<0.05).Compared with the high-dose ART group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the Coumermycin A1 group increased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin decreased(P<0.05).Conclusion ART may inhibit the viability,migration,invasion and EMT of glucose-stimulated CRC cells and promote apoptosis by inhibiting the JAK2/STAT3 signaling pathway.

Objective To explore the value of the Kyoto classification score in differentiating undifferentiated gastric cancer from differentiated gastric cancer,and establish a predictive scoring system for differentiating undifferentiated gastric cancer under endoscope.Methods 183 gastric cancer patients were retrospectively analyzed.According to pathology,95 patients were included in the differentiated group and 88 were included in the undifferentiated group.The age,gender and Kyoto classification score of patients in the two groups were compared,and the factors associated with undifferentiated gastric cancer were screened by binary Logistic regression analysis.The predictive scoring system for undifferentiated gastric cancer was established based on the obtained odds ratio(O(R))values,and the receiver operator characteristic curve(ROC curve)was drawn.Results Compared with differentiated group,the total scores of Kyoto classification,atrophy,intestinal metaplasia and diffuse redness were lower in undifferentiated group(P<0.01).Under the age of 55(P<0.05),female(P<0.05),and C1 atrophy or no atrophy(P<0.01)were independently associated with undifferentiated gastric cancer.The area under the curve(AUC)of predictive scoring system for undifferentiated gastric cancer was 0.881(95％CI:0.828～0.934),and the sensitivity and specificity were 80.70％and 90.50％at the optimal cut-off value.Conclusion There are differences in Kyoto classification scores between undifferentiated and differentiated gastric cancer patients.The predictive scoring system of undifferentiated gastric cancer established by us has certain value in distinguishing undifferentiated gastric cancer under endoscope.

In this study,the immunological characteristics of the PhoP protein were explored with a two-component system of Mycobacterium tuberculosis(Mtb).Bioinformatics was used to predict the B and T cell epitopes of the PhoP protein.A re-combinant expression plasmid was constructed by PCR analysis of the phoP sequence and cloning into the prokaryotic expres-sion vector pET-28a(+).Competent Escherichia coli BL21 cells were transformed with the recombinant plasmid and expres-sion was induced with IPTG.The recombinant PhoP protein was purified by affinity chromatography.Serum levels of PhoP-specific antibodies in Mtb-infected mice and tuberculosis(TB)patients were analyzed with an ELISA.BALB/c mice were im-munized with the PhoP recombinant protein by intramuscular injection.Sera of mice were collected and antibody titers were detected with an ELISA and specificity was assessed by West-ern blot analysis.Mouse splenocytes were isolated and the pro-portions of IFN-y-positive cells and cytokine levels were detec-ted with an ELISpot and ELISA,respectively.Bioinformatics i-dentified 24 B cell and 11 T cell epitopes of the PhoP protein.A prokaryotic recombinant vector of PhoP was successfully con-structed and the recombinant PhoP protein was obtained by purification.Specific antibody levels to PhoP in sera of Mtb in-fected mice and TB patients increased significantly,with preci-sion of 99.9％and 82.5％,and specificity of 100％,respectively.PhoP protein immunization successfully induced production of specific antibodies in mice.Stimulated by antigens in vitro,IL-2 and IFN-γ levels were significantly increased in the splenocytes of immunized mice.Immunization with the PhoP protein induce a humoral immune response and Thl-dominated cellular immu-nity,indicating that the PhoP protein was immunogenic with diagnostic efficacy for TB.These results lay a foundation to clari-fy the role of PhoP in Mtb infection and application for diagnosis and prevention of TB.

Objective:To analyze the clinical characteristics,treatment,and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma(ETP-ALL/LBL).Methods:Clinical data of 113 T lymphoblastic leukemia/lymphoma(T-ALL/LBL)patients from January 2006 to January 2019 were collected from three hematology research centers,including Peking University Third Hospital,the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital,Chinese Medical University.The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients.Results:In 113 T-ALL/LBL patients,13 cases(11.5％)were diagnosed as ETP-ALL/LBL,including 11 males,with a median age of 28(18-53)years.Compared with non-ETP-ALL/LBL patients,there were no significant differences in age,sex,incidence of large mediastinal mass,clinical stage,international prognostic index(IPI)score,white blood cell(WBC)count and lactate dehydrogenase(LDH)level among ETP-ALL/LBL patients.Among 13 ETP-ALL/LBL patients,9 cases(69.2％)achieved complete remission(CR),and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients.Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation(allo-HSCT),ETP-ALL/LBL group had a worse 5-year overall survival(OS)rate compared with non-ETP-ALL/LBL group(0 vs 7.1％,P=0.008),while in patients with allo-HSCT,there was no significant difference for 5-year OS rate between the two group(37.5％vs 40.2％,P＞0.05).Multivariate Cox regression analysis showed that CR after induction therapy,allo-HSCT,and LDH level were independent prognostic factors affecting T-ALL/LBL patients.Conclusion:No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients.Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.

Objective:To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma(DLBCL)in the rituximab era.Methods:The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab,cyclophosphamide,epirubicin,vincristine,prednisone(R-CHOP)or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed.The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed,Logistics regression model was used to analyzed the influencing factors of patients prognosis.Results:A total of 237 patients were enrolled,of which 54.4％(129 cases)were primary extranodal sources of DLBCL,and the most common extranodal sites were as follows:stomach(19.4％),colon(14.7％),tonsils(12.4％),skin/muscle(9.3％),central(7.7％),nasal/nasopharynx(6.2％),bone marrow(5.4％),testes(4.7％).The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow,central,liver,gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin,and the difference was statistically significant(PFS:65.2％vs 76.7％,P=0.008;OS:82.6％vs 88.3％,P=0.04).Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score＞3(OR:0.142,95％CI:0.041-0.495,P=0.002),non-germinal center source(OR:2.675,95％CI:1.069-6.694,P=0.036),and DEL patients(OR:0.327,95％CI:0.129-0.830,P=0.019).An NCCN-IPI score＞3 was the only independent adverse prognostic factor for PFS(OR:0.235,95％CI:0.116-0.474,P＜0.001).Conclusion:Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement,and the overall prognosis is worse than that of patients with lymph node origin.NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.