Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States. AIM: To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents. METHODS: We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared. RESULTS: 49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased. CONCLUSION: IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

[Prevalence Survey of Functional Dyspepsia and Irritable Bowel Syndrome in Chinese College Students Based on Rome â £ Diagnostic Criteria].

Objective: To investigate the prevalence and risk factors of functional dyspepsia (FD) and irritable bowel syndrome (IBS) among college students in China. Methods: An online questionnaire survey of college students aged 17-35 from across China was conducted. The online questionnaire survey was supplemented by an offline survey. A total of 2025 valid samples were included for statistical analysis. χ 2 test and logistic regression were performed for statistical analysis. Results: The prevalence of FD among college students who met the Rome Ⅳ diagnostic criteria was 5.5% (112/2025), with most of them, or 66.1% (74/112), suffering from postprandial discomfort syndrome (PDS). Smoking (odds ratio [ OR]=2.334, 95% confidence interval [ CI]: 1.187-4.589, P=0.014), depression ( OR=2.447, 95% CI: 1.421-4.214, P=0.001), and insomnia ( OR=1.947, 95% CI: 1.291-2.937, P=0.001) were positively correlated with the prevalence of FD. The prevalence of IBS was 1.9% (38/2025), with IBS-diarrhea dominant (IBS-D) being the most important subtype that accounted for 44.7%. Anxiety ( OR=3.63, 95% CI: 1.34-9.88, P=0.012) and insomnia ( OR=2.35, 95% CI: 1.18-4.68, P=0.015) were positively correlated with the prevalence of IBS. Conclusion: Based on Rome Ⅳ criteria, IBS and FD are not uncommon among Chinese university students. Psychological disorders and some related lifestyle factors may be related to the development of the disease. In the future, more series of studies based on different diagnostic criteria, different regions, and multiple factors should be conducted in China.

Glycemic control by umbilical cord-derived mesenchymal stem cells promotes effects of fasting-mimicking diet on type 2 diabetic mice.

BACKGROUND: Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting may impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effect of UC-MSCs on improving the lipid metabolism disorder is not quite satisfactory. We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism. METHODS: C57/BL6 mice were fed with high-fat diet (HFD) to induce a diet-induced obese (DIO) mouse model. Leptin receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: phosphate buffer saline (PBS), UC-MSCs, FMD, and UC-MSCs + FMD. At the end of the study period, mice were fasted and sacrificed, with the measurement of physiological and biochemical indexes. In addition, the fresh liver, skin, and white adipose tissue were analyzed by histology. RESULTS: FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD. CONCLUSIONS: We established a strategy that combined UC-MSC infusion and FMD and was effective in treating T2D, which provided potential approaches for developing novel clinical T2D therapies.

Transmission patterns of COVID-19 in the mainland of China and the efficacy of different control strategies: a data- and model-driven study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has seriously endangered the health and lives of Chinese people. In this study, we predicted the COVID-19 epidemic trend and estimated the efficacy of several intervention strategies in the mainland of China. METHODS: According to the COVID-19 epidemic status, we constructed a compartmental model. Based on reported data from the National Health Commission of People's Republic of China during January 10-February 17, 2020, we estimated the model parameters. We then predicted the epidemic trend and transmission risk of COVID-19. Using a sensitivity analysis method, we estimated the efficacy of several intervention strategies. RESULTS: The cumulative number of confirmed cases in the mainland of China will be 86 763 (95% CI: 86 067-87 460) on May 2, 2020. Up until March 15, 2020, the case fatality rate increased to 6.42% (95% CI: 6.16-6.68%). On February 23, 2020, the existing confirmed cases reached its peak, with 60 890 cases (95% CI: 60 350-61 431). On January 23, 2020, the effective reproduction number was 2.620 (95% CI: 2.567-2.676) and had dropped below 1.0 since February 5, 2020. Due to governmental intervention, the total number of confirmed cases was reduced by 99.85% on May 2, 2020. Had the isolation been relaxed from February 24, 2020, there might have been a second peak of infection. However, relaxing the isolation after March 16, 2020 greatly reduced the number of existing confirmed cases and deaths. The total number of confirmed cases and deaths would increase by 8.72 and 9.44%, respectively, due to a 1-day delayed diagnosis in non-isolated infected patients. Moreover, if the coverage of close contact tracing was increased to 100%, the cumulative number of confirmed cases would be decreased by 88.26% on May 2, 2020. CONCLUSIONS: The quarantine measures adopted by the Chinese government since January 23, 2020 were necessary and effective. Postponing the relaxation of isolation, early diagnosis, patient isolation, broad close-contact tracing, and strict monitoring of infected persons could effectively control the COVID-19 epidemic. April 1, 2020 would be a reasonable date to lift quarantine in Hubei and Wuhan.

Spleen-Associated Effects on Immunity in Hepatitis B Virus-Related Cirrhosis with Portal Hypertension.

Our study aimed to investigate the histologic and immunological changes of portal hypertension (PH) pre- and postsplenectomy in hepatitis B virus (HBV)-related cirrhosis. Peripheral blood samples were obtained from 30 patients with HBV-related cirrhosis and PH at pre- and postsplenectomy time points and from 15 healthy subjects. Spleen tissue specimens were collected from 15 of the patients with HBV-related cirrhosis and from 8 control patients who had undergone splenectomy due to trauma. Immunohistochemical staining was performed to evaluate the immune effector cells and the expression of negative immune regulators. Flow cytometry was used to investigate the immunophenotypes and percentages. The spleen of cirrhotic patients with PH showed extensive depletion of splenic CD4, CD8, and human leukocyte antigen DR cells along with overexpression of the inhibitory receptors programmed death-1 (PD-1) and T cell immunoglobulin domain and mucin domain-3 and their ligands (PD-L2 and galectin-9). Peripheral blood of patients with PH showed remarkable decrease in proportions of CD8 T cell and natural killer (NK) cells and increase in regulatory T (Treg) cells, as well as high expression of PD-1 in CD4/8 T cells. Compared with presplenectomy patients, cirrhotic patients with PH showed increased proportions of CD8 and NK cells, decreased proportion of Treg cells, and decreased expression of PD-1 in peripheral blood CD4/8 T cells after splenectomy. PH-spleen could lead to peripheral tolerance and immunosuppression in HBV cirrhotic patients, and splenectomy may cause beneficial immunological changes.

[Oestrogen inhibits invasion and metastasis of hepatocellular carcinoma MHCC97H cells by regulating the activity of AKT signaling pathway].

OBJECTIVE: To explore the inhibitory effect of estrogen against metastasis of human hepatocellular carcinoma MHCC97H cells and explore the molecular mechanism. METHODS: The inhibitory effect of estrogen on the migration and invasion of MHCC97H cells was evaluated with wound healing assay and Transwell assay. Western blotting was used for investigating the expression of MMP-2, MMP-9, AKT and p-AKT in the cells treated with estrogen. RESULTS: Estrogen treatment significantly inhibited the migration and invasion of MHCC97H cells in a dose-dependent manner. Estrogen significantly down-regulated the protein expressions of MMP-2 and MMP-9 and lowered the phosphorylation level of AKT. CONCLUSION: The anti-metastatic effect of estrogen involves inhibition of MMP-2 and MMP-9 in MHCC97H cells probably by regulating AKT signal pathway.

Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C.

Interstitial pneumonitis (IP) is an uncommon pulmonary complication associated with interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection. Pneumonitis can occur at any stage of HCV treatment, ranging from 2 to 48 wk, usually in the first 12 wk. Its most common symptoms are dyspnoea, dry cough, fever, fatigue, arthralgia or myalgia, and anorexia, which are reversible in most cases after cessation of IFN therapy with a mean subsequent recovery time of 7.5 wk. Bronchoalveolar lavage in combination with chest high resolution computed tomography has a high diagnostic value. Prompt discontinuation of medication is the cornerstone, and corticosteroid therapy may not be essential for patients with mild-moderate pulmonary functional impairment. The severity of pulmonary injury is associated with the rapid development of IP. We suggest that methylprednisolone pulse therapy followed by low dose prednisolone for a short term is necessary to minimize the risk of fatal pulmonary damage if signs of significant pulmonary toxicity occur in earlier stage. Clinicians should be aware of the potential pulmonary complication related to the drug, so that an early and opportune diagnosis can be made.

[Clinical features of interstitial pneumonitis due to interferon alpha therapy for chronic hepatitis C].

OBJECTIVE: To analyze the clinical features of interstitial pneumonitis (IP) associated with interferon therapy for chronic hepatitis C. METHODS: We report the first case of IP in China resulting from pegylated interferon alpha-2a in combination with ribavirin for treatment of hepatitis C viral infection. A statistical analysis of the related literatures documenting such IP cases was performed using SPSS 11.5 software. RESULTS: Of the 22 patients reported to develop IP after interferon therapy alone or in combination with ribavirin, 83%, 72% and 56% of the patients had the symptoms of dyspnoea, dry cough and fever, respectively. Twenty of these cases presented with restrictive pulmonary functional impairment and/or hypoxemia, and diffuse infiltration on chest radiography and/or CT. Complications were documented in 71% of the cases within 12 weeks of the treatment. The majority (85%) of the patients had favorable prognoses with an average recovery time of 7.5 weeks. Compared with the patients with mild and moderate pulmonary function impairment, 8 patients with severe pulmonary functional impairment had early onset of IP during the interferon therapy (6.6 vs 14.1 weeks, P<0.05), and a higher rate of corticosteroid treatment (75% vs 54%, P>0.05). CONCLUSION: IP is a rare pulmonary complication associated with IFN therapy, and patients with chronic hepatitis C should be followed up closely in the first 12 weeks of interferon therapy. Prompt discontinuation of medication is mandatory in the presence of IP, and corticosteroid therapy may not be essential for patients with mild or moderate pulmonary functional impairment under close monitoring. The severity of pulmonary damage is associated with the time of complication occurrence, and corticosteroids are required when obvious pulmonary toxicity occurs in early stage of the treatment (within 6 weeks) to reduce the pulmonary damage.

[Expression of E-cadherin, beta-catenin and cyclin D1 in epidermal skin lesions of patients with active psoriasis vulgaris].

OBJECTIVE: To examine the expressions of E-cadherin, beta-catenin and cyclin D1 in the skin lesions of patients with psoriasis vulgaris, and understand their possible roles in keratinocyte hyperproliferation in these patients. METHODS: Immunohistochemistry was performed to detect the expressions of E-cadherin, beta-catenin and cyclin D1 in the normal skin tissues and psoriatic lesions. RESULTS: In normal skin tissues, positive staining for E-cadherin and beta-catenin was detected in all layers of the normal epidermis at the sites of cell-cell junctions, and downregulation of E-cadherin and beta-catenin expression was found in the granular layer and basal layer of the psoriatic lesions. Cyclin D1 overexpression was observed mainly in the basal layer of the lesions, which was correlated to abnormal expression of beta-catenin. CONCLUSION: Downregulation of E-cadherin and beta-catenin expression and cyclin D1 overexpression in psoriatic skin are probably involved in keratinocyte hyperproliferation in psoriasis vulgaris.

[Expression of E-cadherin and beta-catenin in Bowen's disease and squamous cell carcinoma].

OBJECTIVE: To investigate the involvement of E-cadherin-catenin adhesion system in Bowen's disease (BD) and cutaneous squamous cell carcinoma (SCC). METHODS: Fifteen normal skin, 28 BD and 18 SCC specimens were stained with monoclonal antibodies against E-cadherin and beta-catenin. Evaluation of the staining results was performed with semi-quantification of the pattern and intensity of staining, percentage of positive cells, and cytoplasmic staining. RESULT: Normal skins strongly expressed membranous E-cadherin and beta-catenin, but their expression was remarkably reduced in BD and SCC. Abnormal staining of beta-catenin was observed in the cytoplasm or cell nuclei of BD and SCC. CONCLUSION: Abnormal expression of the E-cadherin/catenin complex is common in SCC and BD.