ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

The therapeutic effects of transcranial magnetic stimulation (TMS) are closely related to the structure of the stimulation coil. Based on this, this study designed an A-word coil and proposed a multi-strategy fusion multi-objective slime mould algorithm (MSSMA) aimed at optimizing the stimulation depth, focality, and intensity of the coil. MSSMA significantly improved the convergence and distribution of the algorithm by integrating a dual-elite guiding mechanism, a hyperbolic tangent control strategy, and a hybrid polynomial mutation strategy. Furthermore, compared with other stimulation coils, the novel coil optimized by the MSSMA demonstrates superior performance in terms of stimulation depth. To verify the optimization effects, a magnetic field measurement system was established, and a comparison of the measurement data with simulation data confirmed that the proposed algorithm could effectively optimize coil performance. In summary, this study provides a new approach for deep TMS, and the proposed algorithm holds significant reference value for multi-objective engineering optimization problems.
Algorithms ; Transcranial Magnetic Stimulation/instrumentation* ; Equipment Design ; Humans

Objective To investigate the expression and prognostic value of microRNA-29b-2-5p(miR-29b-2-5p)and syntaxin 16(STX16)in hepatocellular carcinoma(HCC).Methods The cancer tissues and adjacent tissues of 88 HCC patients diagnosed in Nantong Tumor Hospital from January 2013 to September 2020 were collected.The expressions of miR-29b-2-5p and STX16 in cancer tissues and adjacent tissues were analyzed by real-time fluorescent quantitative PCR.The expression of STX16 protein in cancer tissues and adjacent tissues were analyzed by immunohistochemistry.Pearson correlation analysis was used to analyze the correlation be-tween miR-29b-2-5p and STX16.Non-parametric χ2 test was used to analyze the relationship between the ex-pression of the two proteins and clinicopathological parameters,and Kaplan-Meier survival curve was used to analyze the relationship between the expression of the two proteins and prognosis.Results The relative ex-pression level of miR-29b-2-5p was 0.780(0.351,1.708)in cancer tissues and 1.014(0.458,3.124)in adja-cent tissues in 88 HCC patients.The relative expression level of miR-29b-2-5p in cancer tissues was signifi-cantly lower than that in adjacent tissues(P=0.012).The relative expression level of STX16 mRNA was 0.775(0.406,0.946)in cancer tissues and 0.368(0.080,1.301)in adjacent tissues in 88 HCC patients.The relative expression level of STX16 mRNA in cancer tissues was significantly higer than that in adjacent tissues(P<0.01).Immunohistochemical results showed that STX16 was expressed in the cytoplasm,and the expres-sion of STX16 in cancer tissues was higher than that in adjacent tissues(P<0.05).The expression of miR-29b-2-5p in cancer tissues was related to cancer stage(P<0.05),and the expression of STX16 was related to cancer stage and alpha-fetoprotein(P<0.05).Patients with low miR-29b-2-5p expression had a shorter over-all survival(OS)than those with high miR-29b-2-5p expression,and patients with high STX16 expression had a shorter OS than those with low STX16 expression(P<0.05).Conclusion The expression of miR-29b-2-5p is low and STX16 is high in HCC tissues.The combined detection of miR-29b-2-5p and STX16 can effectively evaluate the prognosis of HCC patients.

Various degrees of post-infection symptoms after novel coronavirus infection are called long COVID or post COVID-19 syndrome.Some of the patients with long COVID syndrome exhibit the symptoms of spontaneous sweating,fatigue and weakness,palpitation and shortness of breath.Following the theory of six-meridian syndrome differentiation and the clinical principle of prescriptions corresponding to syndromes,Professor Li Saimei differentiated the spontaneous sweating of patients with long COVID into four main types,namely spontaneous sweating due to disharmony between taiyang nutritive qi and defensive qi,spontaneous sweating due to Yangming damp-heat,spontaneous sweating due to taiyin cold-damp,and spontaneous sweating due to jueyin blood deficiency,which can be treated with Guizhi Decoction,Gegen Qinlian Decoction,Fuzi Lizhong Decoction,and Danggui Sini Decoction plus Erzhi Pills,respectively.In the view of Professor Li Saimei,spontaneous sweating in patients with long COVID may result from disharmony between nutritive qi and defensive qi,or from damp-heat pathogen,or from cold-damp pathogen,or from deficiency of qi and blood.Therefore,the therapies for spontaneous sweating should be focused on harmonizing nutritive qi and defensive qi,drying dampness and eliminating pathogens,warming meridians and nourishing blood.Moreover,protecting the heart-yin and heart-yang should be taken into account,and herbal medicines with the actions of activating heart-yang and replenishing heart-yin and herbs for tranquilizing and alleviating palpitation can be selected in clinic.

The hepatic vascular microenvironment(HVM)plays a pivotal role in maintaining liver function homeostasis,including metabolism,detoxification,and coagulation.The maintenance of HVM homeostasis is governed by an intricate interplay of mechanical forces,chemical signals,and neuroelectrophysiological conduction.Recent studies have shown that an imbalance in HVM promotes the progression of chronic liver disease(CLD),which is characterized by sinusoidal capillarization,vascular deformation and remodeling,and the arterialization of blood supply.This review sum-marizes the dynamic regulatory mechanisms that underpin HVM in physiological conditions,and the primary pathological manifestations observed at various stages of CLD progression,aiming to provide a robust framework for the development of therapeutic strategies targeting HVM homeostatic imbanlance in CLD.

The hepatic vascular microenvironment(HVM)plays a pivotal role in maintaining liver function homeostasis,including metabolism,detoxification,and coagulation.The maintenance of HVM homeostasis is governed by an intricate interplay of mechanical forces,chemical signals,and neuroelectrophysiological conduction.Recent studies have shown that an imbalance in HVM promotes the progression of chronic liver disease(CLD),which is characterized by sinusoidal capillarization,vascular deformation and remodeling,and the arterialization of blood supply.This review sum-marizes the dynamic regulatory mechanisms that underpin HVM in physiological conditions,and the primary pathological manifestations observed at various stages of CLD progression,aiming to provide a robust framework for the development of therapeutic strategies targeting HVM homeostatic imbanlance in CLD.

Objective To analyze the expression and role of the disulfidptosis-related gene PDZ and LIM domain protein 1(PDLIM1)in various tumors.Methods The expression of PDLIM1 mRNA was analyzed by Xiantao website.The diagnostic and prognostic capabilities of PDLIM1 in 33 types of tumors were explored using the Xiantao website and Sangerbox 3.0 data analysis platform.The correlation between PDLIM1 and clinical classification and its staging was analyzed by the TISIDB database.The correlation between PDLIM1 and tumor immunity was analyzed by Sangerbox 3.0 data analysis platform and Kaplan-Meier Plotter database.Protein-protein interaction networks(PPI)were constructed by STRING database and Cytoscape,and were enriched by Sangerbox 3.0 data analysis platform.Finally,the GSCA website was applied to acquire the expression of PDLIM1 mRNA and its sensitivity to drugs.Results There was heterogeneity in the expression of PDLIM1 mRNA among 33 tumors.PDLIM1 had good diagnostic ability in cholangiocarcinoma(CHOL),glioblastoma multiforme(GBM),kidney renal clear cell carcinoma(KIRC),lung adenocarcinoma(LUAD),ovarian cancer(OV),pancreatic cancer(PAAD),skin cutaneous melanoma(SKCM)and testicular germ cell tumor(TGCT).High expression of PDLIM1 mRNA in glioma,low-grade glioma(LGG),KIPAN,GBM,uveal melanoma(UVM),and adrenocortical carcinoma(ACC)suggested poor prognosis,while low expression in sarcoma suggested poor prognosis.PALIM1 mRNA expression was correlated with the classification of head and neck squamous cell carcinoma(HNSC),kidney renal papillary cell carcinoma(KIRP),uterine corpus endometrial carcinoma(UCEC),uterine carcinosarcomas(UCS),and UVM as well as the staging of cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC),HNSC,UCEC,and LGG.PDLIM1 was significantly associated with immune infiltration of 36 tumors led by prostateadenocarcinoma(PRAD),and was found to have a relatively good prognosis after immunotherapy in patients with high PDLIM1 mRNA expression.PDLIM1 exerted effects on organisms mainly through its involvement in the regulation of actin cytoskeleton,cell adhesion,and cancer-related pathways,and was sensitive to various drugs led by Isoliquiritigenin.Conclusion PDLIM1 was closely related to the clinical prognosis and immune infiltration of a variety of tumors,and it is expected to be a cancer diagnostic and prognostic biomarker or therapeutic target.

Objective::To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.Methods::Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) ( n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CM TK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[ 18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CM TK+in vivo. Cardiac function and morphology were evaluated by echocardiography. Results::The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively ( P < 0.01). Conclusion::A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CM TK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.

Objective::To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.Methods::Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) ( n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CM TK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[ 18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CM TK+in vivo. Cardiac function and morphology were evaluated by echocardiography. Results::The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively ( P < 0.01). Conclusion::A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CM TK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.

OBJECTIVE To evaluate the cost-effectiveness of the first-line treatment using the combination therapy of sugemalimab and chemotherapy (hereinafter referred to as the "combination therapy") for advanced esophageal squamous cell carcinoma (ESCC) with high programmed death-ligand 1 (PD-L1) expression from the perspective of the Chinese healthcare system. METHODS A partitioned survival model was constructed based on data from the GEMSTONE-304 study. The model cycle was set at 3 weeks,with a study duration of 10 years and a discount rate of 5％. The primary output parameters of the model included total costs,quality-adjusted life year (QALY),incremental costs,and incremental cost-effectiveness ratio (ICER). Cost-utility analysis was employed to assess the economic feasibility of the combination therapy compared to chemotherapy alone. The robustness of the base case analysis results was evaluated through univariate sensitivity analysis,probabilistic sensitivity analysis,and scenario analysis. RESULTS The ICER of the combination therapy compared to chemotherapy alone was 288430.35 yuan/QALY,significantly exceeding the willingness-to-pay (WTP) threshold of 173354.52 yuan/QALY which was set at 1.94 times the per capita gross domestic product (GDP) in 2023. The price of sugemalimab was the primary factor influencing the ICER. When the WTP threshold was set at 1.94 times the per capita GDP (173354.52 yuan/QALY),the probability of the combination therapy being cost-effective compared to chemotherapy alone was 0. The combination therapy only became cost-effective compared to chemotherapy alone when the price of the drug dropped to 6107.41 yuan per box (600 mg). CONCLUSIONS From the perspective of the Chinese healthcare system,the combination therapy for first-line treatment of advanced ESCC with high PD-L1 expression is not cost-effective;the combination therapy is cost-effective when the price of sugemalimab decreas by 50.65％.