[Study on mechanism of Chinese Yam polysaccharide synergizing nucleoside analogues against hepatitis B virus through p38 MAPK signaling pathway].

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.

Effect of endoscopic therapy and drug therapy on prognosis and rebleeding in patients with esophagogastric variceal bleeding.

Esophagogastric variceal bleeding (EVB) is one of the common digestive system emergencies with poor prognosis and high rate of rebleeding after treatment. To explore the effects of endoscopic therapy and drug therapy on the prognosis and rebleeding of patients with EVB, and then select better treatment methods to effectively improve the prognosis. From January 2013 to December 2022, 965 patients with EVB who were hospitalized in gastroenterology Department of the 940 Hospital of Joint Logistic Support Forces of PLA were retrospectively analyzed. Patients were divided into endoscopic treatment group (ET, n = 586) and drug treatment group (DT, n = 379). Propensity score matching (PSM) analysis was performed in both groups, and the general information, efficacy and length of hospital stay were recorded. The patients were followed up for 3 months after bleeding control to determine whether rebleeding occurred. There were 286 cases in each group after PSM. Compared with DT group, ET had higher treatment success rate (P < 0.001), lower rebleeding rate (P < 0.001), lower mortality rate within 3 months, and no significant difference in total hospital stay (P > 0.05). Compared with drug therapy, endoscopic treatment of EVB has short-term efficacy advantages, and can effectively reduce the incidence of rebleeding and mortality within 3 months.

Ileal perforation involvement in Wegener granulomatosis comorbid with COVID-19 infection: A case report and review of the literature.

RATIONALE: Granulomatosis with polyangiitis (GPA) is a systematic autoimmune disease. The typical clinical involvement of GPA entails the upper and lower respiratory tracts, and the kidneys. Gastrointestinal (GI) involvement is uncommon and unless detected and treated promptly, may lead to life-threatening complications such as perforation. We aim to review all available publications since the first description in 1982 dealing with GI perforation in patients with Wegener granulomatosis and draw attention to this serious situation. PATIENT CONCERNS: We present a 54-year-old man diagnosed with GPA who presented initially with nasal symptoms and suffered ileal perforation following Corona Virus Disease 2019 infection. We also review previously reported patients with Wegener granulomatosis who had GI perforation to investigate the perforation site and period, pathology, diagnosis, and treatment methods. DIAGNOSES AND INTERVENTIONS: The case of a GPA-diagnosed patient who presented initially with nasal symptoms and suffered ileal perforation following Corona Virus Disease 2019 infection. We recommended a renal puncture biopsy, steroids, and immunosuppressants to improve the patient condition. The patient and his family refused these treatment recommendations. OUTCOMES: Our patient exhibited continued progressive vascular inflammatory changes and eventual irreversible systemic damage. These sequelae were attributed to the patient declining prednisolone and immunosuppressant therapy. LESSONS: GI perforation is rare in GPA but severe complication. Consequently, we recommend that early diagnosis and treatment with steroid hormones and immunosuppressants for GPA patients with GI perforation.

Risk factors of infection among close contacts of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first detected in December 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. METHODS: PubMed, Web of Science, Embase, CNKI, and other databases were searched by computer, and relevant literature published from December 2019 to November 2022 on the influencing factors of infection in close contacts with novel coronavirus pneumonia was collected. Meta-analysis was carried out after literature screening, quality assessment, and data extraction. RESULTS: A total of 425 articles were retrieved and 11 were included. Meta-analysis showed that there were 6 risk factors, and the combined OR value and 95% CI of each influencing factor were 5.23 (3.20, 8.57) for family members, 1.63 (0.56, 4.77) for regular contact, 2.14 (0.62, 7.32) for the elderly, 0.58 (0.001569.89) for cohabitation, 1.97 (1.02, 3.82) for women and 0.75 (0.01, 54.07) for others. The Deeks' funnel diagram indicates that there is no potential publication bias among the included studies. CONCLUSION: Family members and gender differences are the risk factors of infection among close contacts, and it cannot be proved that there are differences in infection among frequent contact, advanced age, and living together.

[Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway].

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.

Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation.

Retiform hemangioendothelioma (RH) is a type of low-grade malignant angiosarcoma. It commonly involves the skin and subcutaneous tissue of the lower extremities, but a few cases have been reported in the gut. However, hepatic RH has not been previously reported. This report presents the case of RH of the liver in a 61-year-old woman who was admitted to the hospital having presented with liver space-occupying lesions of 2 months evolution. The patient underwent an abdominal ultrasound examination, which indicated a hemangioma, but abdominal computed tomography diagnosed a liver abscess. In order to determine the nature of the lesion, an ultrasound-guided liver biopsy was performed, after which a pathological diagnosis confirmed the presence of RH in the liver. The patient underwent ultrasound-guided microwave ablation three times and has been followed up for 8 years with no tumor recurrence or metastasis. Surgical excision is still the first choice for the treatment of hepatic RH. As shown in this case, however, for patients who refuse to undergo surgery or have surgical contraindications, ultrasound-guided microwave ablation is an alternative treatment option. The report of this case expands the scope of liver tumors to a certain extent and provides a reference for clinical diagnosis and treatment.

Expression and Correlation of MIF and ERK1/2 in Liver Cirrhosis and Hepatocellular Carcinoma Induced by Hepatitis B.

Objective: To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular carcinoma (HCC) with a background of HBILC and analyze the correlation of MIF and ERK1/2 with HBILC and HCC. Methods: Twenty cases of normal liver tissues were collected as a control group, and 48 specimens of HBILC tissues and 48 specimens of HCC tissues were collected as the experimental group, which were assigned as the HBILC group and HCC group, respectively. All tissue specimens were processed into tissue chips. The expressions of MIF, ERK1/2, and their phosphorylated proteins were detected via immunohistochemistry, and MIF and ERK1/2 nucleic acid expressions were detected by in situ hybridization. The results were statistically analyzed using the chi-square test. Results: Proteins and nucleic acids of MIF and ERK1/2 presented low expression in the control group and high expression in the HBILC group and HCC group. MIF expression in the three groups was 25.0%, 75.0%, and 79.17%, respectively, while that of the nucleic acids was 25.0%, 70.83%, and 68.75%, respectively. Expression of ERK1/2 in the three groups was 40.0%, 60.42%, and 81.25%, respectively, and that of nucleic acids was 40.0%, 79.17%, and 77.08%. Expression of pERK1/2 was low in the control and HBILC group and high in the HCC group. Expression of pERK1/2 in the three groups was 20%, 45.83%, and 75%, respectively. Expression of pERK1/2 in the HCC group was significantly different from that in the HBILC and control group (P<0.05), but the difference between the HBILC group and control group was not statistically significant (P>0.05). Conclusion: Occurrence and development of HBILC and HCC are not only related to the high expression of MIF but also closely related to the activation of the ERK1/2 signaling pathway.

Research progress of a new immune checkpoint inhibitor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain in anti-tumor immunotherapy / 中国热带医学

@#The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells (NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells. TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies (mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC) patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.

New HIV diagnoses in patients with COVID-19: two case reports and a brief literature review.

BACKGROUND: COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. Immunocompromised patients often present atypical presentations of viral infected diseases. CASE PRESENTATION: We report newly diagnosed HIV infections in two patients with COVID-19 in China. In our two cases, both patients with elevated IL-6 received Tocilizumab treatment, but did not present obvious therapeutic effect. CONCLUSIONS: These cases highlight possible co-detection of known immunocompromised diseases such as HIV. The two cases we reported stressed the risk of misdiagnosis, especially during the pandemic of an infectious disease and the importance of extended testing even if in immune-compromised condition the immune state may be ignored.

Matrine inhibits proliferation and migration of HepG2 cells by downregulating ERK1/2 signaling pathways.

OBJECTIVE: To research the effect of matrine on the proliferation and migration of HepG2 cells through extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. METHODS: HepG2 cell was selected and divided into blank control group, experimental group (matrine 1, 2, and 4 mg/mL), and positive control group (PD98059, ERK1/2 inhibitor). MTT measure was used to detect the effective time and concentration which matrine inhibits HepG2 cells. After 24 h, the effect of effective concentration of matrine on the of morphological changing HepG2 cells was observed. The invasion ability was assayed by transwell method, the expression of ERK1/2 and pERK1/2 were detected through Western blot, and reverse transcription polymerase chain reaction was used to test the expression level of ERK1/2 mRNA. RESULTS: With the increase of matrine concentration, the number of adherent HepG2 cells gradually decreased, the morphologic changes gradually became spherical, some cell morphology was incomplete, and even cell fragments appeared. The proliferation and invasion ability of HepG2 cells decreased. The expression of ERK1/2, pERK1/2, and ERK1/2 mRNA downregulated with the increase of matrine concentration (P < 0.05). CONCLUSION: Matrine inhibits the proliferation and migration of HepG2 cells by downregulating the ERK1/2 signaling pathway.

Type I enteropathy-associated T-cell lymphoma in the colon of a 29-year-old patient and a brief literature review.

Enteropathy-associated T-cell lymphoma (EATL) is a rare gastrointestinal non-Hodgkin's lymphoma, originating from intraepithelial T-lymphocyte, which is specifically associated with celiac disease. EATL most commonly presents in the sixth and seventh decades of life. We report a unique case of type I EATL in the colon with liver metastasis, which was presented with nonspecific radiological findings and at a very young age (29 years old) compared with previously published data. We suggest that EATL should be regarded as part of differential diagnosis in any patient presenting with abdominal pain, diarrhea, weight loss, and malabsorption because delay in treatment can result in an irreversible clinical outcome.

High altitude increases the expression of hypoxia-inducible factor 1α and inducible nitric oxide synthase with intest-inal mucosal barrier failure in rats.

BACKGROUND: The failure of intestinal mucosal barrier may induce multiple organ dysfunction and systemic inflammatory response syndrome, but little work has been done on whether hypobaric hypoxia related to the failure of intestinal mucosal barrier. AIMS: To study the expression of hypoxia-inducible factor 1α (HIF-1α), inducible nitric oxide synthase (iNOS) and morphological changes of intestinal mucosa in albino rats at different altitude. METHODS: 30 male Wistar rats raised in plain for one month were randomly divided into 3 groups: Plain 500 m group (n=10), High-altitude (HA) 3842 m group (n=10) and HA4767 m group (n=10). Each group was delivered to different altitude area at the same shipping time and executed after 3 days' exposure to different altitude. Intestinal segments with the same location of all rats were removed for morphological analyses. Morphologic parameters (villous height, crypt depth, mucosal wall thickness and villous surface area) were measured by optical and scanning electron microscope. The expression of iNOS and HIF-1α were detected by immunohistochemistry. RESULTS: Morphological indexes in higher altitude groups were exacerbated obviously compared with those of lower altitude groups. While the expression of iNOS and HIF-1α in higher altitude groups were significantly increased than those of lower altitude groups. Linear correlation analysis showed that the expression of iNOS was positively correlated with that of HIF-1α. CONCLUSIONS: Hypobaric hypoxia increases the expression of HIF-1α and iNOS in intestinal mucosa, however exacerbates the mucous morphologic parameters with altitude increasing. HIF-1α may regulate the expression of iNOS and be involved in the damage of intestinal mucosa.

Activation of autophagy in rats with plateau stress-induced intestinal failure.

Hypobaric hypoxia may damage the intestinal mucosa, which may induce multiple organ dysfunction. However, little work has been done regarding whether high altitude hypoxia is associated with failure of the intestinal mucosal barrier. The aim of this study was to investigate the change of the autophagy after the intestinal failure in rats acutely exposed to plateau stress. Fifty Wistar rats were randomly divided into five groups: the plain group, plateau for 6 h, 12 h, 24 h, and 48 h (n = 10 in each group). The acute exposure to plateau was established at a simulated altitude of 4767 meters (m) in a decompression chamber. Intestinal injury was verified by light microscopy. The autophagosomes in the intestinal epithelial cells were observed by transmission electron microscopy (TEM). The protein expression of Beclin1 and LC3B in the intestinal epithelial cells were analyzed by immunohistochemistry. Compared with the plain group, acute exposure to plateau led to a time-dependent damage of the intestinal epithelium. The autophagosome was observed after the intestinal failure following acute exposure to high altitude for 6 h. The expression of Beclin1 and LC3B protein in the rats exposed to acute plateau for 6 h, 12 h, 24 h and 48 h were significantly higher than those in the plain group. The expression of autophagy also showed a significant increase in rats with intestinal failure following acute exposure to plateau stress.

Expression of breast cancer resistance protein in peripheral T cell subsets from HIV­1­infected patients with antiretroviral therapy.

The aim of the present study was to investigate the expression of breast cancer resistance protein (BCRP) in peripheral T cell subsets of human immunodeficiency virus 1 (HIV­1)­infected patients, and to analyze the association between the levels of BCRP expression and disease progression in HIV­1 infection. Peripheral blood mononuclear cells (PBMCs) were obtained from HIV­1­infected patients (n=118), including 92 patients with antiretroviral therapy (ART) and 26 patients without a history of ART. Control samples from 30 healthy donors were also analyzed. The expression levels of BCRP in T cells were evaluated by flow cytometry. A high inter­individual variability was observed in CD4+ and CD8+ T cells in the HIV­1­infected patients and healthy donors; however, the analyzed expression levels of BCRP were significantly higher in the HIV­1­infected group with ART than those in the group with no history of ART (P<0.01). Furthermore, the frequency of BCRP­expressing T cells was inversely correlated with CD4+ and CD8+ T cell counts in HIV­1­infected patients with ART. The results suggested that BCRP expression varied among HIV­1­infected patients and healthy donors but was significantly higher in HIV­1 patients undergoing ART. In conclusion, the present study suggested that overexpression of BCRP may be involved in disease progression of the HIV­1 infection and may participate in drug resistance to ART, thus contributing to the failure of highly active ART in HIV­1 therapeutics.

Gene profiling in the dynamic regulation of the lifespan of the myelin sheath structure in the optic nerve of rats.

Aging of the nervous system leads to impairments in cognition and motor skills, and is a major risk factor for several neurological disorders. Recently, numerous nerve function deficits that appear with aging have been found to be a consequence of myelin abnormalities; however, the genetic mechanism of the age­related alterations in the myelin sheath has not yet been fully elucidated. In the present study, the morphology of the myelin sheath in the optic nerve of rats was analyzed at 10 time­points throughout life. Marked alterations in the myelin sheath were observed in aging and aged optic nerves, and these became progressively more severe with time. To determine the biological processes affected by aging in the myelin sheath, the age­related profiling of the myelin sheath in rat optic nerves was established using microarray hybridization at 10 time­points throughout life, between birth and senescence. From the results, 3,826 transcripts associated with the age­related alterations in the myelin sheath of the optic nerve were identified. It was found that the biological processes most significantly altered by aging were lipid metabolism, the immune response and transmitter transport. This suggests that the downregulation of lipid synthesis genes and the upregulation of immune and neurotransmitter transport genes in aging may be the genetic basis for the age­related alterations observed in the myelin sheath.

Effects of normal aging on myelin sheath ultrastructures in the somatic sensorimotor system of rats.

Previous studies have presented qualitative and quantitative data regarding the morphological changes that occur peripherally in myelin sheaths and nerve fibers of rats during their lifespan. However, studies on ultrastructural features of myelinated fibers (MFs) in the central nervous system (CNS) remain limited. In the present study, morphological analyses of the somatic sensorimotor MFs in rats at time­points between postnatal day 14 and postnatal month (PNM) 26 were conducted using electron microscopy. Significant alterations in the myelin sheath were observed in the sensorimotor system of aging and aged rats, which became aggravated with age. The ultrastructural pattern of myelin lamellae also exhibited age dependence. The transformation of the myelin intraperiod line from complete to incomplete fusion occurred after PNM 5, leading to an expansion of periodicity in myelin lamellae. These pathological changes in the myelin structure occurred very early and showed a significant correlation with age, indicating that myelin was the part of the CNS with the highest susceptibility to the influence of aging, and may be the main target of aging effects. In addition to the myelin breakdown, continued myelin production and remyelination were observed in the aging sensorimotor system, suggesting the presence of endogenous mechanisms of myelin repair.

Expression levels of P-glycoprotein in peripheral blood CD8+ T lymphocytes from HIV-1-infected patients on antiretroviral therapy.

In this study, we aimed to measure P-glycoprotein (P-gp) expression in CD8(+) T lymphocytes of HIV-1-infected patients, to investigate how P-gp levels are affected by antiretroviral therapy (ART) in HIV-1 infection, and to assess the value of using P-gp expression to predict virologic response to ART. Peripheral blood mononuclear cells (PBMCs) were obtained from a cohort of HIV-1­infected patients in China: 140 patients on ART, and 49 ART-naïve patients. We also enrolled 24 healthy blood donors as the controls. The expression levels of P-gp in CD8(+) T cells of HIV-1-infected patients were evaluated by quantitative reverse transcription PCR, ELISA and flow cytometry. A high inter-individual variability was observed in the CD8(+) T cells of both HIV-1-infected patients and healthy donors; however, the expression levels of P-gp were significantly higher in the HIV-1-infected group on ART compared to the ART-naïve group. The relative proportion of P-gp(+)CD8(+) T cells inversely correlated with the blood CD4(+) T cell count in the HIV-1­infected patients on ART (r=-0.3343, P=0.0375). Groups of both good and poor responders showed significantly elevated levels of P-gp(+)CD8(+) T cells. The percentage of P-gp(+)CD8(+) T cells appeared to provide a sensitive estimate of the virologic response to ART compared to the CD4(+) T cell count. Our results suggest that P-gp expression varies among HIV-1­infected patients, but is significantly higher in HIV-1­infected patients on ART. The overexpression of P-gp is involved in ART initiation during HIV-1 infection, and P-gp(+)CD8(+) T cells may be an additional criterion for the evaluation of the antiretroviral response to ART.