Hidatidosis mesentérica y hepática en la costa caribe colombiana. Reporte de caso / Mesenteric and hepatic hydatid disease on the Colombian Caribbean coast. Case report

Introducción. La hidatidosis o equinococosis es una zoonosis parasitaria que se adquiere al ingerir huevos de cestodos del género Echinococcus. El diagnóstico clínico raramente se hace en sitios no endémicos. La mayoría de los pacientes se encuentran asintomáticos y los hallazgos incidentales en los estudios de imágenes o en procedimientos quirúrgicos permiten la sospecha diagnóstica. Caso clínico. Paciente masculino de 70 años, residente en área rural del municipio de Puerto Libertador, departamento de Córdoba, Colombia, quien consultó por masa abdominal en epigastrio y mesogastrio, parcialmente móvil e indolora. Resultados. En cirugía se identificaron lesiones quísticas mesentérica y hepática. Después de la cirugía y mediante estudios de inmunohistoquímica, se confirmó el diagnóstico de quiste hidatídico. El paciente tuvo una evolución satisfactoria. Conclusión. La hidatidosis quística mesentérica y hepática sintomática es una enfermedad rara en sitios no endémicos, donde la cirugía constituye un pilar fundamental en el diagnóstico y tratamiento, sumado al manejo médico farmacológico.

Introduction. Hydatidosis or echinococcosis is a parasitic zoonosis that is acquired by ingesting eggs of cestodes of the genus Echinococcus. Clinical diagnosis is rarely made in non-endemic sites. Most patients are asymptomatic and incidental findings on imaging studies or surgical procedures allow for diagnostic suspicion. Clinical case. A 70-year-old male patient, resident in a rural area of the municipality of Puerto Libertador, department of Córdoba, Colombia, who consulted for an abdominal mass in the epigastrium and mesogastrium, partially mobile and painless. Results. In surgery, mesenteric and hepatic cystic lesions were identified. After surgery and through immunohistochemistry studies, the diagnosis of hydatid cyst was confirmed. The patient had a satisfactory evolution. Conclusion. Symptomatic mesenteric and hepatic cystic hydatidosis is a rare disease in non-endemic sites, where surgery constitutes a fundamental pillar in the diagnosis and treatment in addition to pharmacological medical management.

Manifestaciones dermatológicas de la cirrosis hepática: revisión de la literatura / Dermatological manifestations of liver cirrhosis: review of the literature

La piel y sus anexos tienen amplia relación con todos los órganos y sistemas. Los cambios presentes en estos pueden ser el primer hallazgo en un paciente con enfermedad hepática, encontrándose hasta en el 20 % de los casos, por lo que las manifestaciones extrahepáticas adquieren importancia, y aunque muchas de estas no son específicas, algunos marcadores dermatológicos pueden ayudar al diagnóstico de la enfermedad y se pueden correlacionar con su severidad. El desarrollo de las lesiones cutáneas en los pacientes con cirrosis hepática se genera principalmente por hipertensión portal y exceso de estrógenos circulantes, por lo tanto, su tratamiento se basa en el manejo de la patología hepática subyacente. En el presente artículo se hace una revisión de la literatura y se describe un amplio espectro de manifestaciones dermatológicas asociadas a cirrosis hepática, con sus características y etiopatogénesis, siendo las más frecuentes la ictericia, el prurito, los nevus en araña, el eritema palmar, las venas en cabeza de Medusa, y los cambios de uñas y del vello, entre otras.

The skin and its annexes have a broad relationship with all organs and systems. Changes present in these can be the initial finding in a patient with liver disease, occurring in up to 20% of cases, therefore the extrahepatic manifestations become important, and although many of these are not specific, some dermatological markers can help in the diagnosis of the disease and may correlate with its severity. The development of cutaneous lesions in patients with liver cirrhosis is mainly generated by portal hypertension and excess of circulating estrogens, therefore their treatment is based on managing the underlying liver pathology. This article reviews the literature and describes a wide range of dermatological manifestations associated with liver cirrhosis, with their characteristics and etiopathogenesis, being the most frequent jaundice, pruritus, spider nevus, palmar erythema, caput Medusae veins, nail and hair changes, among others.

Dendrobium Officinale Polysaccharide Alleviates Hepatic Fibrosis via Epithelial-Mesenchymal Transition / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl4-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl4 olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl4 induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.

Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism / 中国药房

OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe （HBR） combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group （normal saline）， and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups： model group （normal saline， ig）， HBR group （0.69 g/kg， ig）， oxaliplatin group （10 mg/kg， ip）， and combination group （intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin）， with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days； administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment， the general condition of nude mice in each group was observed， and the tumor volume was measured every 4 days. On the 30th day of administration， the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate， spleen coefficient， the number of red blood cells， white blood cells and platelets in the whole blood of nude mice in each group， and the content of aspartate aminotransferase （AST） and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 （LC3），selective autophagy adaptor protein p62， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Caspase-3 protein in tumor tissues. RESULT Compared with the model group， the tumor volume， tumor weight， white blood cells，red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased （P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly increased （P＜0.05 or P＜0.01）. Compared with the oxaliplatin group， the tumor volume and tumor weight of nude mice in the combination group were significantly decreased （P＜0.01）； the white blood cells， red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased （P＜0.05 or P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly decreased （P＜0.01）； the expression levels of LC3， Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased （P＜0.01）， and the expression levels of p62 and Bcl-2 proteins were significantly decreased （P＜0.01）. CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy， and can alleviate the peripheral neurotoxicity， hematological toxicity， hepatorenal toxicity， and immune organ toxicity caused by oxaliplatin in nude mice.

Study on the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis / 中国药房

OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.

Research advances in traditional Chinese medicine regulation of programmed cell death in intervening against hepatic fibrosis / 临床肝胆病杂志

Hepatic fibrosis （HF） is a pathological process of abnormal repair of liver tissue structure caused by chronic liver injury， and its pathogenesis has not been fully clarified. Related studies have shown that programmed cell death may be associated with the onset of HF， and traditional Chinese medicine （TCM） has a significant effect in regulating programmed cell death to intervene against HF. This article reviews the main mechanism of the influence of programmed cell death on HF and discusses the possible mechanism of TCM regulation of programmed cell death in improving HF， which provides new ideas for TCM prevention and treatment of HF.

Abnormal liver biochemical parameters in pregnancy during the epidemic of coronavirus disease 2019 / 临床肝胆病杂志

ObjectiveTo investigate the differences in abnormal liver biochemical parameters in pregnant patients during the epidemic or non-epidemic period of coronavirus disease 2019 （COVID-19）. MethodsA retrospective analysis was performed for 539 pregnant women who were discharged from Department of Obstetrics， Peking University First Hospital， from October 2017 to March 2022 and had at least one abnormal liver biochemical parameter among alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBil）， and total bile acid. The patients in the epidemic period of COVID-19 and those in the non-epidemic period of COVID-19 were compared in terms of etiology， coagulation parameters， aminotransferases， bile acid， and renal function. The independent samples t-test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsAmong the patients discharged from Department of Obstetrics during the non-epidemic period of COVID-19， 262 had abnormal liver biochemical parameters， accounting for 1.46%， while 277 patients had abnormal liver biochemical parameters during the epidemic period of COVID-19， accounting for 1.73% among the patients discharged from Department of Obstetrics during the same period of time， and there was a significant difference between these two groups （χ2=3.947， P=0.047）. The etiological analysis of the patients with abnormal liver biochemical parameters during the two periods showed that there was no difference in the proportion of patients with four pregnancy-specific liver diseases （hyperemesis gravidarum， preeclampsia and eclampsia， intrahepatic cholestasis of pregnancy， and acute fatty liver of pregnancy）. As for the patients with abnormal liver biochemical parameters in pregnancy， there was no significant difference in the proportion of patients with normal creatinine and stimated glomerular filtration rate （eGFR） between the epidemic period and the non-epidemic period （86.78% vs 87.90%， χ2=0.141， P=0.708）. The patients with ALT≥5×upper limit of normal accounted for 7.94% in the epidemic period of COVID-19 and 9.54% in the non-epidemic period （χ2=0.433， P=0.511）， and the patients with severe cholestasis accounted for 7.75% in the epidemic period of COVID-19 and 9.27% in the non-epidemic period （χ2=0.392， P=0.531）. The proportion of patients with obstetric bleeding during the epidemic period of COVID-19 was significantly lower than that during the non-epidemic period （14.61% vs 24.19%， χ2=489.334， P<0.001）. ConclusionThere is no difference in the proportion of patients with pregnancy-specific liver diseases among the patients with abnormal liver biochemical parameters in pregnancy between the epidemic period and the non-epidemic period of COVID-19， and there is no change in the proportion of patients with normal creatinine and eGFR among these patients in the epidemic period of COVID-19.

Role and mechanism of action of phytoestrogen biochanin A in improving liver fibrosis in ovariectomized mice / 临床肝胆病杂志

ObjectiveTo investigate the effect of phytoestrogen biochanin A （BCA） on liver fibrosis induced by CCl4 in female mice with bilateral oophorectomy （ovariectomized） and its mechanism. MethodsA total of 50 ovariectomized Kunming mice were selected and given intraperitoneal injection of CCl4 to establish a model of liver fibrosis， and then according to body weight， they were randomly divided into model group， positive control group， and low-， middle-， and high-dose BCA groups， with 10 mice in each group. In addition， 10 female mice in the same litter were given resection of a small amount of adipose tissue near both ovaries to establish the sham-operation group. The mice in the positive control group were given estradiol 2 mg/kg by gavage， and those in the low-， middle-， and high-dose BCA groups were given BCA by gavage at a dose of 25， 50， and 100 mg/kg， respectively， once a day for 7 consecutive weeks； the mice in the sham-operation group and the model group were given an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage. The mice were anesthetized and sacrificed after administration to collect samples. Liver index and uterus index were measured； HE staining and Masson staining were used to observe liver histopathological changes； the biochemical analysis was used to measure the activity of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； ELISA was used to measure the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in liver tissue， and Western blot was used to measure the relative protein expression levels of collagen Ⅰ， transforming growth factor-beta 1 （TGF-β1）， alpha-smooth muscle actin （α-SMA）， estrogen receptor beta （ERβ）， and p-NF-κBp65/NF-κBp65 in liver tissue. The t-test was used for comparison of continuous data between two groups； a one-way analysis of various was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsCompared with the sham-operated group， the model group had a significant increase in liver index and a significant reduction in uterus index， as well as significant increases in the activities of serum AST and ALT， the levels of IL-6 and TNF-α in liver tissue， and the protein expression levels of collagen Ⅰ， TGF-β1， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in the expression of ERβ in liver tissue （P>0.05）， and the model group showed significant fibrosis lesions in the liver， such as hepatocyte edema， steatosis， and necrosis with inflammatory cell infiltration and hyperplasia， deposition， and staggered distribution of collagen fibers. Compared with the model group， the low-， middle-， and high-dose BCA groups had significant reductions in liver index， the activities of serum AST and ALT， the levels of IL-6 and TNF-α， and the protein expression levels of collagen Ⅰ， TGF-β1， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in uterine index （P>0.05）， as well as a significant increase in the protein expression level of ERβ in liver tissue （P<0.05） and varying degrees of improvement in liver fibrosis lesions. ConclusionBCA can effectively improve CCL4-induced liver fibrosis in ovariectomized female mice， possibly by upregulating ERβ to inhibit the NF-κB signaling pathway and then alleviating inflammatory response.

Changes in the total volume and contour density of oval cells in hepatic lobules of rats with carbon tetrachloride-induced hepatic fibrosis： A stereological study / 临床肝胆病杂志

ObjectiveTo quantitatively investigate the changes in the total volume and contour density of hepatic oval cells （HOC） in hepatic lobules of rats with carbon tetrachloride （CCl4）-induced hepatic fibrosis. MethodsA total of 11 healthy male Sprague-Dawley rats were randomly divided into control group with 5 rats and hepatic fibrosis group with 6 rats， and CCl4 and olive oil suspension were injected subcutaneously twice a week， 3 mL/kg each time. After five weeks of hepatic fibrosis modeling， five liver tissue blocks with a size of about 1 mm3 were randomly selected from the liver of each rat to prepare one Epon812 epoxy resin-embedded ultrathin section， and the stereological method and transmission electron microscopy were used for the quantitative analysis of the total volume and contour density of HOC in the hepatic lobules of rats. In addition， four liver tissue blocks with a thickness of 2 mm were randomly selected from the remaining liver of each rat to prepare two paraffin-embedded Masson staining sections， and the degree of liver fibrosis in each rat was qualitatively evaluated according to the Metavir staging criteria for liver fibrosis. The independent-samples t test was used for comparison of continuous data between groups. ResultsThe quantitative stereological analysis showed that the total volume of HOC in hepatic lobules was 15.40±7.63 mm3 in the control group and 146.80±114.00 mm3 in the liver fibrosis group， and compared with the control group， the total volume of HOC in hepatic lobules of rats in the liver fibrosis group was significantly increased by 8.53 times （t=-2.551， P=0.031）； the contour density of HOC in hepatic lobules was 56.20±40.40 in the control group and 566.50±317.00 in the liver fibrosis group， and compared with the control group， the contour density of HOC in hepatic lobules of rats in the liver fibrosis group was significantly increased by 9.08 times （t=-3.539， P=0.006）. Qualitative observation showed that liver fibrosis stage of rats reached stage Ⅱ-Ⅲ according to the Metavir scoring criteria， and massive proliferation of HOC was observed around the proliferation site of hepatic stellate cells in the perisinusoidal space of rats. ConclusionCCl4 induces significant proliferation of HOC in hepatic lobules of rats with liver fibrosis.

Research advances in hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Hepatic sinusoidal obstruction syndrome （HSOS）， also known as hepatic veno-occlusive disease， is hepatic vascular disease of hepatic sinusoidal obstruction and hepatic venular occlusion and fibrosis due to various causes. This article systematically elaborates on the research advances in HSOS from the aspects of understanding and naming， etiology and pathogenesis， clinical manifestation， diagnosis and differential diagnosis， prevention， and treatment. HSOS can occur in patients receiving bone marrow hematopoietic stem cell transplantation， radiotherapy/chemotherapy， and medication containing pyrrolidine alkaloids， and the common clinical manifestations of HSOS include abdominal distension， distending pain in the liver area， ascites， jaundice， and hepatomegaly. The diagnostic criteria for HSOS vary with etiology， and it needs to be differentiated from other diseases such as drug-induced liver diseases and hepatic venous outflow tract obstruction. Defibrotide and low-molecular-weight heparin have a therapeutic effect on HSOS associated with hematopoietic stem cells and pyrrolidine alkaloids， respectively， and there are currently no effective drugs for HSOS caused by oxaliplatin chemotherapy.

Experimental study of Lentinan antagonizes against hepatic lipid deposition induced by sodium arsenite in mice / 公共卫生与预防医学

Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.

Efficacy of Tiaogan Huaxian Pills in Prevention and Treatment of Hepatic Fibrosis in Hepatitis B and Its Effect on Diffusion-weighted Imaging / 中国实验方剂学杂志

ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

Advances in the treatment of acute hepatic porphyria / 临床肝胆病杂志

Acute hepatic porphyria （AHP） is a rare disease with abnormal heme metabolism， and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods， this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage， including RNAi therapy， enzyme replacement therapy， genetic supplementation of DNA or mRNA， drug molecular chaperones， and glycine transporter inhibitors for reducing heme synthesis. Moreover， this article also reviews the treatment of AHP-related comorbidities and complications， such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China， and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP， and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.

Value of MRI biliary score and liver/muscle ratio in evaluating the pathological grade of liver fibrosis / 临床肝胆病杂志

ObjectiveTo investigate the value of biliary score and hepatic signal intensity-to-muscle signal intensity ratio （HMR） obtained by multiphase contrast-enhanced MRI scan using Gd-EOB-DTPA in evaluating the pathological grade of liver fibrosis. MethodsA retrospective analysis was performed for the MRI and clinical data of 51 patients with chronic hepatitis B liver fibrosis in Wuming Hospital Affiliated to Guangxi Medical University from January 2020 to May 2023. The 51 patients with liver fibrosis were divided into low-grade group （S1-S2） and high-grade group （S3-S4）. GE Architact 3.0T MR scanner was used to perform MRI scans， including routine plain scan and contrast-enhanced scan at arterial phase， portal venous phase， delayed phase， hepatobiliary phase， and excretory phase， and biliary score and HMR were measured for the patients with different grades of liver fibrosis. The t-test was used for comparison of continuous data between groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the value of MRI indicators in determining the pathological grade of liver fibrosis. ResultsAmong the 51 patients with liver fibrosis， there were 30 patients in the low-grade group and 21 in the high-grade group. Compared with the high-grade group， the low-grade group had significantly higher biliary score （3.67±0.55 vs 2.57±0.75， t=6.05， P<0.001） and HMR at portal venous phase （2.38±0.76 vs 1.97±0.18， t=2.41， P=0.020）， delayed phase （2.48±0.70 vs 1.99±0.27， t=3.09， P=0.003）， and hepatobiliary phase （4.10±0.63 vs 3.16±0.47， t=5.81， P<0.001）. The above indicators had an area under the ROC curve （AUC） of 0.86， 0.79， 0.82， and 0.88， respectively， in distinguishing low- and high-grade liver fibrosis， with a positive rate of 70%， 63.3%， 83.3%， and 96.7%， respectively， and a negative rate of 90%， 95.2%， 74.1%， and 100%， respectively， in the diagnosis of high-grade liver fibrosis. Biliary score combined HMR had an AUC of 0.95， with a positive rate of 85.7% and a negative rate of 96.7%. ConclusionBiliary score and HMR at hepatobiliary phase obtained by multiphase contrast-enhanced MRI scan using Gd-EOB-DTPA has a relatively high diagnostic efficacy in distinguishing between low- and high-grade liver fibrosis and a certain guiding value for the diagnosis and treatment of liver fibrosis in clinical practice.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-l ,4-dione on resisting hepatic fibrosis induced by CC14 in rats and its mechanisms via TGF-pi/Smads signaling pathway / 中国药理学通报

Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis / 中国血吸虫病防治杂志

Objective To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection / 中国血吸虫病防治杂志

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

Expression of neutrophil extracellular traps and phagocytic functions among patients with hepatic alveolar echinococcosis / 中国血吸虫病防治杂志

Objective To investigate the expression of neutrophil extracellular traps (NETs) and phagocytic function in the peripheral blood of patients with hepatic alveolar echinococcosis (HAE), and to examine their correlations with clinical inflamma tory indicators and liver functions. Methods A total of 50 patients with HAE admitted to Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qinghai University from August 2022 to June 2023 were enrolled, while 50 age- and gender-matched healthy individuals from the Centre for Healthy Examinations of the hospital during the same period served as controls. The levels of NETs markers neutrophil myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using enzyme-linked immunosorbent assay (ELISA). Peripheral blood neutrophils were isolated using density gradient centrifugation, stimulated in vitro using phorbol 12-myristate 13 acetate (PMA), and the levels of MPO and citrullination histone H3 (CitH3) released by neutrophils were quantified using flow cytometry. The phagocytic functions of neutrophils were examined using flow cytometry. In addition, the correlations of MPO and NE levels with clinical inflammatory indicators and liver biochemical indicators were examined using Spearman correlation analysis among HAE patients. Results The peripheral blood plasma MPO［(417.15 ± 76.08) ng/mL vs. (255.70 ± 80.84) ng/mL; t = 10.28, P < 0.05］, NE［(23.16 ± 6.75) ng/mL vs. (11.92 ± 3.17) ng/mL; t = 10.65, P < 0.05］and CitH3 levels［(33.93 ± 18.93) ng/mL vs. (19.52 ± 13.89) ng/mL; t = 4.34, P < 0.05］were all significantly higher among HAE patients than among healthy controls, and a lower phagocytosis rate of neutrophils was detected among HAE patients than among healthy controls［(70.85 ± 7.32)% vs. (94.04 ± 3.90)%; t = 20.18, P < 0.05］, and the ability to produce NETs by neutrophils was higher among HAE patients than among healthy controls following in vitro PMA stimulation. Pearson correlation analysis showed that the phagocytosis rate of neutrophils correlated negatively with platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) level and C-reactive protein (CRP) level (rs = −0.515 to −0.392, all P values < 0.05), and the MPO and NE levels positively correlated with inflammatory markers NLR, PLR, CRP and IL-6 (rs = 0.333 to 0.445, all P values < 0.05) and clinical liver biochemical indicators aspartic transaminase, alanine aminotransferase, direct bilirubin and total bilirubin among HAE patients (rs = 0.290 to 0.628, all P values < 0.001). Conclusions Excessive formation of NETs is found among HAE patients, which affects the phagocytic ability of neutrophils and results in elevated levels of inflammatory indicators. NETs markers may be promising novel biomarkers for early diagnosis, monitoring, and severity assessment of liver disease.