The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Appendicular lean mass and the risk of stroke and Alzheimer's disease: a mendelian randomization study.

BACKGROUND: Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer's disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. METHODS: A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). RESULTS: The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89-0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85-0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77-0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73-0.89; P < 0.001). Regarding multivariable MR analysis, ALM retained the stable effect on AIS when adjusting for BMI, LDL-C, and AF, while a suggestive association was observed after adjusting for T2DM. And the estimated effect of ALM on LAS was significant after adjustment for BMI and AF, while a suggestive association was found after adjusting for T2DM and LDL-C. Besides, the estimated effects of ALM were still significant on SVS and AD after adjustment for BMI, T2DM, LDL-C, and AF. CONCLUSIONS: The two-sample MR analysis indicated that genetically predicted ALM was negatively related to AIS and AD. And the subgroup analysis of AIS revealed a negative causal effect of genetically predicted ALM on LAS or SVS. Future studies are required to further investigate the underlying mechanisms.

Lower serum creatinine to cystatin C ratio associated with increased incidence of frailty in community-dwelling elderly men but not in elderly women.

BACKGROUND: Sarcopenia has been reported to play an important role in frailty syndrome. The serum creatinine/serum cystatin C ratio (Scr/Cys C ratio) has recently been recognized as a valuable indicator for assessing sarcopenia. However, few studies have examined the association between serum creatinine/serum cystatin C ratio and frailty. The objective of this study is to investigate the relationship between the serum creatinine/serum cystatin C ratio and frailty among older adults residing in the community. METHODS AND MATERIALS: A Total of 1926 community-dwelling older adults aged ≥ 60 years in the 2011 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The participants' frailty status was determined using a 39 item frailty index (FI), which classified individuals as "robust" (FI ≤ 0.1), "pre-frailty" (0.1 < FI < 0.25), or "frailty" (FI ≥ 0.25). The Scr/Cys C ratio was determined by dividing the serum creatinine level (mg/dL) by the cystatin C level (mg/L). The one-way analysis of variance(ANOVA) and Chi-squared test (χ2)were applied to compare the differences between the 3 groups. Both linear regression and logistic regression models were used to further investigate the relationship between Scr/Cys C ratio and frailty. RESULTS: After adjusting for potential confounding factors, the study revealed that participants in the Q1 quartile of Scr/Cys C ratio had increased odds of frailty (Q1vs.Q4: OR = 1.880, 95% CI 1.126-3.139, p = 0.016) compared with those in the Q4 quartile group. In fully adjusted logistic regression models, male participants in the Q2 quartile of Scr/Cys C ratio were significantly correlated with higher odds of pre-frailty (Q2 vs.Q4: OR = 1.693, 95%CI 1.040-2.758, p = 0.034). However, this correlation was not observed in females (OR = 0.984, 95% CI 0.589-1.642, p = 0.950,). Additionally, the study observed an increase in both the frailty index and the incidence of frailty as age increased in both males and females. CONCLUSION: Among community-dwelling older adults, lower Serum creatinine to cystatin C ratio were found to be associated with increased odds of frailty prevalence in males.

Parishin alleviates vascular ageing in mice by upregulation of Klotho.

Senescence of vascular endothelial cells is the major risk of vascular dysfunction and disease among elderly people. Parishin, which is a phenolic glucoside derived from Gastrodia elata, significantly prolonged yeast lifespan. However, the action of parishin in vascular ageing remains poorly understood. Here, we treated human coronary artery endothelial cells (HCAEC) and naturally aged mice by parishin. Parishin alleviated HCAEC senescence and general age-related features in vascular tissue in naturally aged mice. Network pharmacology approach was applied to determine the compound-target networks of parishin. Our analysis indicated that parishin had a strong binding affinity for Klotho. Expression of Klotho, a protein of age-related declines, was upregulated by parishin in serum and vascular tissue in naturally aged mice. Furthermore, FoxO1, on Klotho/FoxO1 signalling pathway, was increased in the parishin-intervened group, accompanied by the downregulated phosphorylated FoxO1. Taken together, parishin can increase Klotho expression to alleviate vascular endothelial cell senescence and vascular ageing.

Impact of the COVID-19 pandemic and the dynamic COVID-zero strategy on HIV incidence and mortality in China.

BACKGROUND: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Chinese government implemented the dynamic COVID-zero strategy. We hypothesized that pandemic mitigation measures might have reduced the incidence, mortality rates, and case fatality ratios (CFRs) of the human immunodeficiency virus (HIV) in 2020-2022. METHOD: We collected HIV incidence and mortality data from the website of the National Health Commission of the People's Republic of China from January 2015 to December 2022. We compared the observed and predicted HIV values in 2020-2022 with those in 2015-2019 using a two-ratio Z-test. RESULTS: From January 1, 2015, to December 31, 2022, a total of 480,747 HIV incident cases were reported in mainland China, of which 60,906 (per year) and 58,739 (per year) were reported in 2015-2019 (pre-COVID-19 stage) and 2020-2022 (post-COVID-19 stage), respectively. The average yearly HIV incidence decreased by 5.2450% (from 4.4143 to 4.1827 per 100,000 people, p <  0.001) in 2020-2022 compared with that in 2015-2019. However, the average yearly HIV mortality rates and CFRs increased by 14.1076 and 20.4238%, respectively (all p <  0.001), in 2020-2022 compared with those in 2015-2019. During the emergency phase in January 2020 to April 2020, the monthly incidence was significantly lower (23.7158%) than that during the corresponding period in 2015-2019, while the incidence during the routine stage in May 2020-December 2022 increased by 27.4334%, (all p <  0.001). The observed incidence and mortality rates for HIV decreased by 16.55 and 18.1052% in 2020, by 25.1274 and 20.2136% in 2021, and by 39.7921 and 31.7535% in 2022, respectively, compared with the predicted values, (all p <  0.001). CONCLUSIONS: The findings suggest that China's dynamic COVID-zero strategy may have partly disrupted HIV transmission and further slowed down its growth. Without China's dynamic COVID-zero strategy, HIV incidence and deaths in the country would have likely remained high in 2020-2022. There is an urgent need to expand and improve HIV prevention, care, and treatment, as well as surveillance in the future.

IL-17A contributes to skeletal muscle atrophy in lung cancer-induced cachexia via JAK2/STAT3 pathway.

Cachexia is a complex metabolic syndrome that occurs in approximately 50% of patients with cancer. Skeletal muscle atrophy is the primary clinical feature. Interleukin (IL)-17A, a proinflammatory factor, plays an important role in many chronic inflammatory diseases. Here, we describe a novel signaling pathway through which IL-17A induced muscle atrophy. We conducted a retrospective clinical study to investigate the relationship between IL-17A and the skeletal muscle index in patients with lung adenocarcinoma. We also investigated the involvement of JAK2/STAT3 signaling pathway regarding the main features of cachexia by injecting Lewis lung carcinoma (LLC) cells into C57BL/6 mice as a model to replicate cancer-induced cachexia. In vitro, C2C12 myotubes were treated with recombinant IL-17A, anti-IL-17A monoclonal antibody, STAT3 inhibitor AG490, and LLC-conditioned medium. Cell viability and aging were also evaluated. We found that in cancer conditions, increased serum levels of IL-17A were related to muscle wasting. JAK2/STAT3 phosphorylation was observed in the muscle of LLC tumor-bearing mice, accompanied by decreased MHC/Myog levels and increased MuRF1/Atrogin-1 levels. Administration of anti-IL-17A monoclonal antibody and AG490 slowed muscle atrophy development. Consistent with the in vivo findings, C2C12 myotubes treated with IL-17A and LLC-conditioned medium demonstrated phosphorylated JAK2/STAT3 signaling, resulting in MHC loss and myotube atrophy. IL-17A also inhibited C2C12 cell proliferation, cell cycle breaking, and cellular senescence. Our results identify that phosphorylation of IL-17A/JAK2/STAT3 signaling pathway appears to be an important component in the pathogenesis of LLC tumor-induced cachexia. Targeted therapy of IL-17A may be a promising approach to reduce skeletal muscle loss in patients with cancer.

Paraneoplastic myelitis associated with durvalumab treatment for extensive-stage small cell lung cancer.

Paraneoplastic neurologic syndromes(PNSs) caused by immune checkpoint inhibitors(ICIs) is rare and requires clinicians to differentiate between disease progression and immune-related adverse effects(irAEs). We hereby report the case of immune-related myelitis accompanied by positive paraneoplastic autoantibodies following durvalumab treatment for extensive-stage small cell lung cancer (ES-SCLC). A 70-year-old Chinese woman with ES-SCLC was administered durvalumab with etoposid-platinum(EP) as first-line treatment. Four cycles after treatment with EP plus ICI, she developed immune-related myelitis with positive paraneoplastic autoantibodies (CV2, SOX1, ZIC4). Spinal MRI showed diffuse abnormal signal shadow in the cervicothoracic spinal cord. She was discontinued for chemotherapy, and treated with high-dose steroids, intravenous immunoglobulin and plasmapheresis, maintenance therapy with steroids resulted in a favorable neurologic outcome. This is the first report of durvalumab-related PNSs. We supposed that the development of paraneoplastic myelitis was causally related to immune activation by durvalumab. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of paraneoplastic myelitis.

Sarcopenia is associated with the presence of nonalcoholic fatty liver disease in Zhejiang Province, China: a cross-sectional observational study.

BACKGROUND: Currently, both non-alcoholic fatty liver disease (NAFLD) and sarcopenia have attracted extensive attention in public health. However, the relationship between NAFLD and sarcopenia remains unclear. This study aimed to clarify the sex-specific association between sarcopenia and NAFLD according to the Asian Working Group for Sarcopenia (AWGS). METHODS: Dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography were measured in 578 participants (92 men and 486 women) during their annual health examinations. Multivariate logistic regression models were used to explore the association between NAFLD and sarcopenia with its two components. RESULTS: A total of 154 participants (30 men and 124 women) had NAFLD. The prevalence of sarcopenia was higher among the participants with NAFLD than among those without NAFLD (men: 20.0% vs. 9.7%, P = 0.295, women: 15.3% vs. 8.0%, P = 0.019). Low muscle mass (LMM) was independently associated with NAFLD in both men and women (men: odds ratio [OR], 2.88; 95% confidence interval [CI] 1.52-5.46; women: OR, 2.08; 95% CI 1.63-2.67). However, low muscle strength (LMS) was independently associated with NAFLD only in male participants, with an OR of 1.15 (95% CI 1.02-1.28). CONCLUSION: The occurrence of sarcopenia was associated with a higher risk of NAFLD, especially in men, as demonstrated by lower muscle mass and lower muscle strength.

Ultrasound for Measuring the Cross-Sectional Area of Biceps Brachii Muscle in Sarcopenia.

Background: Ultrasound is emerging as an effective method for measuring muscle mass in elderly people. It has been applied in numerous studies to obtain measurement of lower limbs. The study aims to explore the relationship between sarcopenia and ultrasound measurements of biceps brachii. Methods: Participants (n=179) aged over 60 years were enrolled from the first affiliated hospital of Zhejiang University. The muscle thickness (MT), cross-sectional area (CSA) and fat thickness (FT) of these participants were recorded. Spearman test and partial correlation test was used to determine the correlation between indicators. Mann-Whitney U test was performed to compare ultrasonic parameters between sarcopenia group and non-sarcopenia group. The binary logistic regression analysis was employed to detect the potential indicators and prediction equation of sarcopenia. Receiver operating characteristic (ROC) curve analysis was performed for the accuracy of equation. Results: The prevalence of sarcopenia were 16.3% and 10.8% respectively in men and women. CSA was significantly lower in sarcopenia group than non-sarcopenia group in women (P<0.05). CSA was positively correlated with skeletal muscle mass index (SMI) and grip strength (men: r=0.460, 0.433; women: r=0.267, 0.392). After controlling of age and BMI, these correlations disappeared. Binary logistic regression analysis showed that age (OR=1.149, 95%CI: 1.060-1.246; P=0.001) and CSA (OR=0.465, 95%CI: 0.225-0.963; P=0.039) was significant indicators associated with sarcopenia. Area Under Curve was 0.822 (95%CI: 0.725-0.919, P<0.001) for the prediction equation composed of age, gender and CSA for sarcopenia. Conclusion: CSA of the biceps brachii measured with ultrasound is an important indicator associated with sarcopenia.

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

BACKGROUND: Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. METHODS: Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. RESULTS: Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. CONCLUSIONS: H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted.

Chemoresistance is associated with overexpression of HAX-1, inhibition of which resensitizes drug-resistant breast cancer cells to chemotherapy.

Acquired resistance to standard chemotherapy is the common and critical limitation for cancer therapy. Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) has been reported to be upregulated in numerous cancers. However, the role of HAX-1 in oncotherapy remains unclear. In this study, we established MDA-MB-231 cell lines which were resistant to cisplatin (MDA-MB-231/CR) or doxorubicin (MDA-MB-231/DR) to study the chemoresistance in breast cancer. As a result, the HAX-1 which is an apoptosis-associated protein was observed to be overexpressed in both MDA-MB-231/CR and MDA-MB-231/DR compared with the routine MDA-MB-231 cells. Moreover, knockdown of HAX-1 via RNA interference decreased IC50 level of cisplatin by 70.91% in MDA-MB-231/CR cells, and the IC50 level of doxorubicin was decreased by 76.46% in MDA-MB-231/DR cells when the HAX-1 was downregulated. Additionally, we found that the knockdown of HAX-1 induced the release of cytochrome C from mitochondria, resulting in the activation of caspases. Taken together, our study indicates that the overexpression of HAX-1 is essential in the development of chemoresistance in breast cancer. Furthermore, we identify that HAX-1 may become the target for cancer therapy.

Acute Kidney Infarction Due to Left Ventricular Thrombus Embolization In Patient with Isolated Left Ventricular Noncompaction: A Case Report.

Noncompaction of the ventricular myocardium (NVM) is a rare congenital cardiomyopathy that is characterized by multiple prominent trabeculations and deep intertrabecular recesses, and occurs due to arrest of normal embryogenesis of the endocardium and myocardium. It is also referred to as isolated left ventricular noncompaction (LVNC), because lesions are mainly in the left ventricle. The main clinical manifestations are heart failure, arrhythmia, systemic embolism, and sudden death. Systemic embolism is related to the occurrence of atrial arrhythmias or thrombus formation in the left ventricle. Most resulting thromboembolisms are cerebral or in the arteries of the lower limbs, and renal artery embolisms are rare. There are reports of a few previous cases of renal infarction with diagnoses of NVM on echocardiography, but a thrombus from the left ventricle has never been identified as the cause of a renal artery embolism. This paper reports a 53-year-old male who was admitted to our hospital for LVNC and renal infarction. He had a history of atrial fibrillation 3 years previously. We diagnosed LVNC with a thrombus in the left ventricle using echocardiography. The patient was discharged after renal replacement therapy and treatment with an anticoagulant. During the 2 years of follow-up, his condition remained stable.

The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.

In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95% CI 0·50, 1·67; P< 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95% CI - 0·18, 0·54; P= 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95% CI - 0·32, 0·44; P= 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.

Alterations of Bacteroides sp., Neisseria sp., Actinomyces sp., and Streptococcus sp. populations in the oropharyngeal microbiome are associated with liver cirrhosis and pneumonia.

BACKGROUND: The microbiomes of humans are associated with liver and lung inflammation. We identified and verified alterations of the oropharyngeal microbiome and assessed their association with cirrhosis and pneumonia. METHODS: Study components were as follows: (1) determination of the temporal stability of the oropharyngeal microbiome; (2) identification of oropharyngeal microbial variation in 90 subjects; (3) quantitative identification of disease-associated bacteria. DNAs enriched in bacterial sequences were produced from low-biomass oropharyngeal swabs using whole genome amplification and were analyzed using denaturing gradient gel electrophoresis analysis. RESULTS: Whole genome amplification combined with denaturing gradient gel electrophoresis analysis monitored successfully oropharyngeal microbial variations and showed that the composition of each subject's oropharyngeal microbiome remained relatively stable during the follow-up. The microbial composition of cirrhotic patients with pneumonia differed from those of others and clustered together in subgroup analysis. Further, species richness and the value of Shannon's diversity and evenness index increased significantly in patients with cirrhosis and pneumonia versus others (p < 0.001, versus healthy controls; p < 0.01, versus cirrhotic patients without pneumonia). Moreover, we identified variants of Bacteroides, Eubacterium, Lachnospiraceae, Neisseria, Actinomyces, and Streptococcus through phylogenetic analysis. Quantitative polymerase chain reaction assays revealed that the populations of Bacteroides, Neisseria, and Actinomycetes increased, while that of Streptococcus decreased in cirrhotic patients with pneumonia versus others (p < 0.001, versus Healthy controls; p < 0.01, versus cirrhotic patients without pneumonia). CONCLUSIONS: Alterations of Bacteroides, Neisseria, Actinomyces, and Streptococcus populations in the oropharyngeal microbiome were associated with liver cirrhosis and pneumonia.

The protective role of interleukin-18 binding protein in a murine model of cardiac ischemia/reperfusion injury.

IL-18, a proinflammatory cytokine, is produced by macrophages, epithelial cells, T cells, neutrophils, NK-T cells, and B cells, and has been implicated in the pathophysiology of a variety of inflammatory diseases including ischemia/reperfusion (IR) injury, transplant rejection, and autoimmune disease. Recent study indicated that neutralization of IL-18 with anti-IL-18 antibody or IL-18-binding protein (IL-18BP) ameliorates IR-induced myocardial injury. However, the mechanism needs to be further investigated. In our current study, syngeneic heterotopic heart transplantation was performed by a modified non-suture cuff technique. We found that IL-18BP treatment ameliorated cardiomyocyte necrosis and infiltration of CD4(+) T cells, neutrophils, and macrophages. IL-18BP-treated mice exhibited decreased expression of inflammatory cytokines including IL-1ß, IL-23, IL-18, and IL-17. IL-18BP treatment suppressed Th17 differentiation in vivo and in vitro. Adoptive transfer of T cells from IL-18BP-treated mice showed alleviated cardiac IR injury when compared with that transferred from control mice. Furthermore, the decreased infiltration of mononuclear cells and production of troponin T (TnT) induced by IL-18BP treatment were both abrogated by additional administration of recombinant mouse IL-17 (rmIL-17). These data revealed a protective role of IL-18BP in cardiac IR injury. Above all, IL-18BP ameliorates cardiac IR injury in part through suppression of Th17 differentiation.

[Therapeutic effects and mechanisms of androgen and simvastatin on osteoporosis in castrated rats].

OBJECTIVE: To study the therapeutic effects and mechanisms of androgen and simvastatin on osteoporosis in castrated rats. METHODS: Fifty 12-month-old male SD rats were divided into five groups randomly: castrated group (A), sham operated group (B), androgen group (C), simvastatin group (D), androgen+ simvastatin group (E). Each group has 10 rats. In this study, osteoporosis model was established by castration.All the groups were given testis and epididymis resection except sham operated group. The drugs were administrated on 9 weeks after operation. C, D and E group were treated by the different drugs lavage for 12 weeks. A and B group were given normal saline at the same time. Lumbar spine bone mineral densities (BMD) of rats were measured on pre-operation, before administration, 6 weeks and 12 weeks after administration.All rats were sacrificed on 12 weeks after administration. Serum osteocalcin (BGP), interleukin-6 (IL-6) and Ca2+ were measured. Bone histology was observed. RESULTS: After the treatment by simvastatin or androgen for 12 weeks, BMD of the group C and group D was significantly higher than that of group A (P<0.01). After the treatment by simvastatin and androgen for 6 weeks, BMD of the group E was significantly higher than that of group A, C and D (P<0.05). The level of serum BGP in group A was significantly lower than that in group B (P<0.05) and the level of serum BGP in group E was significantly higher than that in group B (P<0.05). The serum IL-6 in each treated group were significantly lower than that in group A (P<0.05). CONCLUSION: The combination of simvastatin and androgen could inhibit bone absorption and promote bone formation, which could improve the osteoporosis.

An analysis of microbiota-targeted therapies in patients with avian influenza virus subtype H7N9 infection.

BACKGROUND: Selective prophylactic decontamination of the digestive tract is a strategy for the prevention of secondary nosocomial infection in patients with avian influenza virus subtype H7N9 infection. Our aim was to summarize the effectiveness of these therapies in re-establishing a stable and diverse microbial community, and reducing secondary infections. METHODS: Comprehensive therapies were dependent on the individual clinical situation of subjects, and were divided into antiviral treatment, microbiota-targeted therapies, including pro- or pre-biotics and antibiotic usage, and immunotherapy. Quantitative polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE) were used for real-time monitoring of the predominant intestinal microbiome during treatment. Clinical information about secondary infection was confirmed by analyzing pathogens isolated from clinical specimens. RESULTS: Different antibiotics had similar effects on the gut microbiome, with a marked decrease and slow recovery of the Bifidobacterium population. Interestingly, most fecal microbial DGGE profiles showed the relative stability of communities under the continual suppression of the same antibiotics, and significant changes when new antibiotics were introduced. Moreover, we found no marked increase in C-reactive protein, and no cases of bacteremia or pneumonia, caused by probiotic use in the patients, which confirmed that the probiotics used in this study were safe for use in patients with H7N9 infection. Approximately 72% of those who subsequently suffered exogenous respiratory infection by Candida species or multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae were older than 60 years. The combination of probiotics and prebiotics with antibiotics seemed to fail in these patients. CONCLUSIONS: Elderly patients infected with the influenza A (H7N9) virus are considered a high-risk group for developing secondary bacterial infection. Microbiota restoration treatment reduced the incidence of enterogenous secondary infection, but not exogenous respiratory infection. The prophylactic effects of microbiota restoration strategies for secondary infection were unsatisfactory in elderly and critically ill patients.

Epidemiological Features of Hepatitis C in China From 2015 to 2021: Insights From National Surveillance Data.

The COVID-19 pandemic overwhelmed national health care systems, not least in the context of hepatitis elimination. This study investigates the effects of the pandemic response on the incidence rate, mortality rate, and case fatality rate (CFR) for hepatitis C virus (HCV) cases in China. We extracted the number of hepatitis C cases and HCV-related deaths by month and year for 2015 to 2021 in China and applied two proportional tests to analyze changes in the average yearly incidence rates, mortality rates, and CFRs for 2015 to 2020. We used the autoregressive integrated moving average model to predict these three rates for 2020 based on 2015 to 2019 HCV data. The incidence of hepatitis C decreased by 7.11% and 1.42% (P < .001) in 2020 and 2021, respectively, compared with 2015 to 2019, while it increased by 6.13% (P < .001) in 2021 relative to 2020. The monthly observed incidence in 2020 was significantly lower (-26.07%) than predicted. Meanwhile, no differences in mortality rate or CFR were observed between 2021, 2020, and 2015 to 2019. Our findings suggest that nonpharmaceutical interventions and behavioral changes to mitigate COVID-19 could have reduced hepatitis C incidence and accelerated China's implementation of a plan to eliminate HCV infection.

Effects of autocrine vascular endothelial growth factor (VEGF) in non-small cell lung cancer cell line A549.

It is reported that the autocrine loop of the vascular endothelial growth factor (VEGF) is crucial for the survival and proliferation of non-small cell lung cancer (NSCLC) tumors. In this study we aimed to systematically investigate the role of autocrine vascular VEGF in NSCLC cell line A549 through inhibition of endogenous VEGF. A549 cells were transfected with florescence-labeled VEGF oligodeoxynucleotide with lipofectamine. For the experimental group, cells were transfected with VEGF anti-sense oligodeoxynucleotide (ASODN), sense oligodeoxynucleotide (SODN) and mutant oligodeoxynuleotide (MODN) respectively. For the control group cells were mock transfected with lipofectamine or culture medium. At indicated time point after transfection, the expression levels of VEGF mRNA and protein in A549 cells were analyzed by RT-PCR and ELISA respectively. Cell viability was measured by the MTT assay. Cell cycle distribution was detected by flow cytometry. As revealed by RT-PCR assay, the mRNA level of VEGF in cells transfected with ASDON was significantly lower than the other four groups (P < 0.05) at 24 and 48 h after transfection. ELISA assay yielded similar result with significantly decreased level of VEGF protein expression (P < 0.05). The survival fraction of A549 cells transfected with ASDON was significantly lower than the other four groups (P < 0.05) at 24 h after transfection. Also the percentage of G2 phase cells of ASODN group was significantly lower than other four groups. Our data indicate that VEGF expression is efficiently inhibited in A549 cells by ASODN transfection and this inhibition leads to inhibited cell growth and impaired cell cycle distribution.