Co-infection of hepatitis D virus （HDV） and hepatitis B virus （HBV） is the most severe form of viral hepatitis and is associated with accelerated progression of liver disease and a significant increase in the risk of liver cirrhosis and hepatocellular carcinoma. Nucleo（s）tide analogues for HBV treatment are ineffective against HDV infection， necessitating the urgent need for developing specific and effective antiviral therapies for HDV. In recent years， significant advances have been made in the research and development of specific antiviral drugs against HDV， including entry inhibitors targeting viral entry （Bulevirtide） and monoclonal antibody drugs （Libevitug）， which bring ground-breaking advances in the treatment of HDV infection. This article briefly reviews the latest research advances in therapeutic drugs for HDV， introduces the mechanism of action and clinical research data of new drugs recently approved for the treatment of HDV， and discusses the challenges that need to be solved in the field of HDV treatment， in order to provide a reference for understanding the current status of hepatitis D treatment.

ObjectiveTo investigate the mechanism by which Xiebai San regulates respiratory tract and intestinal mucosal immunity in rats with allergic asthma. MethodsForty male SD rats were randomly divided into four groups based on body weight: control group, model group, positive control group, and Xiebai San group. The model group, positive control group, and Xiebai San group were sensitized with ovalbumin to establish a rat model of allergic asthma. From day 21 (the aerosol challenge phase), each group received daily gavage interventions simultaneously: the positive control group was administered dexamethasone (0.068 mg/kg), the Xiebai San group received Xiebai San solution (2 g/mL, 11.3 mL/kg), while the control and model groups were given an equal volume of normal saline, once daily for 14 consecutive days. After euthanasia, lung and intestinal tissues were collected. Hematoxylin and eosin staining was used to observe histopathological changes. Transmission electron microscopy was employed to examine tissue ultrastructure. Immunohistochemistry was applied to detect the positive reaction areas of phosphatidyl-inositol 3-kinase (PI3K) and protein kinase B (Akt) proteins. Total protein and total RNA were extracted from lung and intestinal tissues, then the protein and mRNA expression levels of PI3K and Akt genes were detected by Western blotting and real-time quantitative PCR, respectively. ResultsHistopathological results showed alveolar emphysema accompanied by inflammatory cell infiltration, and intestinal mucosal injury with inflammatory cell infiltration in the model group as compared with the control group; the cellular structure of lung tissues was disrupted in the model group, with reduced organelles, while the ultrastructural lesions in the intestine were relatively mild. Compared with the model group, Xiebai San group exhibited milder pathological changes in lung tissues, with occasional alveolar wall damage and a small amount of inflammatory cell infiltration; the intestinal mucosal structure was improved, glands were arranged regularly, and pathological changes such as tissue loosening and inflammatory infiltration were alleviated; the cellular structure of lung tissues was relatively intact with reduced severity of lesions, and no ultrastructural pathological changes were observed in intestinal tissues. Immunohistochemistry and Western blotting results showed that compared with the control group, the specific positive reaction areas of PI3K and Akt in lung and intestinal tissues were significantly increased in the model group (all P<0.001); meanwhile, the protein expression levels of PI3K and Akt were significantly upregulated (all P<0.05). Compared with the model group, the positive area of Akt protein in lung tissue was significantly reduced in the Xiebai San group (P<0.001), and the positive area of PI3K in intestinal tissue was also significantly decreased (P<0.000 1). Additionally, the protein expression levels of PI3K and Akt in lung and intestinal tissues were significantly downregulated (all P<0.01). Real-time quantitative PCR results showed that compared with the control group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly elevated in the model group (all P<0.05). Compared with the model group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly reduced in the Xiebai San group (all P<0.05). ConclusionXiebai San exerts protective effects on rats with allergic asthma by inhibiting the expression of key nucleic acids and proteins in the PI3K-Akt signaling pathway in lung and intestinal tissues, improving the morphological structure of lung tissue, and maintaining intestinal mucosal integrity, and regulating intestinal mucosal immune function.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

ObjectiveTo evaluate a novel nomogram based on contrast-enhanced MRI radiomics combined with clinical variables for the preoperative prediction of perineural invasion （PNI） in intrahepatic cholangiocarcinoma （ICC）. MethodsThe clinical data of 59 ICC patients were retrospectively collected. According to postoperative pathology reports， the patients were divided into the non-PNI group （n = 33） and the PNI group （n = 26）. Regions of interest （ROI） were delineated from five MRI sequences. Radiomics features were then extracted and filtered to select those with the strongest discriminative power for PNI identification. These selected features were used to construct a radiomics model， which subsequently generated a quantitative radiomics score （radiomics score， Radscore）. Univariate analysis was applied to identify clinical variables associated with PNI， and the glm function was subsequently used to construct clinical and combined models. Finally， the models were evaluated using receiver operating characteristic （ROC） curves， calibration curves， and decision curve analysis （DCA）. The combined model was then visualized as a nomogram. ResultsThe clinical model included age， carbohydrate antigen 19-9 （CA19-9）， red blood cell distribution width， and albumin， whereas the Radscore included five radiomic features. The areas under the ROC curves （AUCs） for the clinical and radiomics models were 0.717 （95%CI： 0.586-0.848） and 0.896 （95%CI： 0.820-0.973）， respectively， whereas the combined model further improved its AUC to 0.917 （95% CI：0.848-0.987）. The calibration curves and DCA showed that the nomogram was well calibrated and provided the greatest net clinical benefit. ConclusionThe novel nomogram may serve as a basis for preoperative prediction of PNI status， thereby assisting clinical decision-making and guiding personalized treatment.

Cerebral blood flow directly affects the metabolism of substances and neural activity in the brain, and is closely associated with the occurrence and development of cerebral small vessel disease (CSVD). Multiple studies have revealed that various imaging biomarkers in patients with CSVD, such as lacunar infarction, enlarged perivascular spaces, cerebral microbleeds, cerebral atrophy, and white matter hyperintensities, are closely associated with cerebral autoregulation (CA) function. Therefore, understanding the regulatory mechanism of CA in patients with CSVD is of great significance for delaying the further development of CSVD, improving cerebral ischemia and cognitive impairment. This article reviews the correlation and mechanism between CA and CSVD.

Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67％(49/60)in the observation group versus 70.00％(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P＜0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P＜0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P＜0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.

Objective To investigate the knee disorders and risk factors in electromechanical soldiers of a warship,so as to provide a basis for prevention and treatment measures.Methods The knee disorders and treatment data of 200 electromechanical soldiers(study group)and 200 soldiers from other departments(control group)were colected by questionnaire survey and medical records.Results The incidence of knee diseases was 37.5%(75 cases)in the study group,which was significantly higher than that in the control group(16.0%,32 cases,P＜0.05).Traumatic and degenerative diseases were the main types of knee disorders.Age and body mass index were the influencing factors of knee disorders in electromechanical soldiers.Conclusion There is a high incidence of knee disorders in electromechanical soldiers,which is related to a variety of factors.Appropriate prevention and treatment measures are of great significance to reduce the incidence of knee disorders,promote rapid recovery,and reduce non-combat casualty.

Objective To explore the feasibility,effectiveness,and safety of balloon catheter-assisted total hepatic vascular exclusion.Methods We designed and manufactured an endovascular catheter with three lumens and double balloons,which can be inserted into the retrahepatic inferior vena cava through the femoral vein.The superior and inferior vena cava of the liver can be blocked by filling balloon,and the total hepatic vascular exclusion was achieved by combining with pringle method.In animal experiments,total hepatic vascular exclusion was performed by balloon catheter-assist method(experimental group)or traditional methods(control group),and the complete time was compared between the two groups.Blood flow blocking effect was observed by angiography and incision of retrahepatic inferior vena cava under direct vision.The complications were recorded.Results Total hepatic vascular exclusion was successfully completed in both groups.The completion time in the experimental group was significantly shorter than that in the control group([12.5±1.2]min vs.[35.8±4.9]min,P<0.05).CT angiography,DSA,and direct vision of blood vessels all confirmed the effectiveness of balloon catheter-assisted hepatic blood flow exclusion.No catheter displacement,balloon rupture,or air embolism occurred.Conclusion The balloon catheter-assisted hepatic total vascular exclusion is simpler and more feasible than traditional method.

Objective Fasting hypometabolism regulation technology has broad application potential in long-term space flight and survival in extreme extraterrestrial environments.In-depth research on the substrate conversion of energy metabolism and the formation of new steady states under fasting hypometabolism will provide theoretical basis and experimental data support for formulating effective prolonged fasting application mode.Methods 30 SD rats were randomly divided into control group and fasting group(fasting for 1,2,3,and 5 days).Blood biochemical examination,qRT-PCR,and western blotting were performed to analyze the body weight,blood biochemistry,and expression changes of genes and proteins related to glucose and lipid metabolism during different fasting periods.Results Prolonged fasting significantly reduced the body weight,blood glucose,and triglyceride levels of rats;increased the blood ketone level,and replaced glucose as the main energy substance in the body.There are temporal and tissue-specific changes as a whole.Hepatic and renal gluconeogenesis play major roles respectively during different fasting periods.As the fasting time prolongs,the level of hepatic gluconeogenesis gradually decreases,the content of FFA in the blood increases,the expression level of genes related to fat synthesis decreases,fatty acid oxidation is enhanced,and the expression level of the key gene HMGCS2 for ketone body generation increases.Conclusion During prolonged fasting,there is a significant conversion of glucose-ketone energy supply substrates,and a new steady state of energy metabolism mainly supplied by ketone bodies is formed within 2-5 days of fasting.The body maintains a low metabolic state by regulating changes in key genes in pathways such as glucose and lipid metabolism.