Prevalence of Mycobacterium bovis in deer in mainland China: a systematic review and meta-analysis.

Background: Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis. Methodology: This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses. Results: In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). Elaphurus davidianus was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis. Conclusion: Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.

Seroprevalence and potential risk factors of brucellosis in sheep from America, Africa and Asia regions: A systematic review and meta-analysis.

BACKGROUND: Brucellosis, a neglected and global zoonotic disease, infect a variety of mammals, among which sheep are one of the main hosts. This disease results in huge economic losses and is a widespread concern around the world. RESULT: Based on the selection criteria, 40 articles from 2010 to 2021 of five databases (CNKI, Wanfang, VIP, PubMed and Science Direct) reported in America, Africa and Asia were included. The data showed that during this period, the overall seroprevalence of sheep brucellosis on these three continents was 6.2%. At the regional level, sheep brucellosis had the highest seroprevalence (8.5%) in Africa and the lowest seroprevalence (1.9%) in the Americas. With regard to the age of the sheep, the seroprevalence was significantly higher in adult sheep (15.5%) than in lambs (8.6%). Further, the seroprevalence was significantly higher in sheep that had abortion (44.3%) than in pregnant (13.0%) and non-pregnant sheep (9.5%). With regard to herd size, herds with >20 sheep (35.4%) had a significantly higher seroprevalence than herds with <20 sheep (16.8%). In terms of farming and grazing mode, free-range rearing (8.4%) was associated with a significantly higher seroprevalence than intensive farming (2.8%), and mixed grazing (37.0%) was associated with a significantly higher seroprevalence than single grazing (5.7%). CONCLUSION: Sheep brucellosis is widely distributed in sheep-rearing regions of America, Africa and Asia, and sheep are susceptible to brucellosis by themselves or from other infectious sources. Therefore, timely monitoring of ovine brucellosis and improving farming and grazing patterns are critical to reducing the prevalence of brucellosis.

Safety and effectiveness for oral intake of carbohydrate-rich drink at preoperative 2 hours before painless colonoscopy.

The aim of this study was to evaluate the feasibility, safety, and optimal dose of oral intake of carbohydrate-rich drinks 2 hours before painless colonoscopy. All patients receiving painless colonoscopy were randomly divided into 3 groups: control group (no carbohydrate-rich drink, n = 33), low-dose group (5 mL/kg carbohydrate-rich drink, n = 30), and high-dose group (8 mL/kg carbohydrate-rich drink, n = 30). Use of vasoactive drugs, the visual analog scale including thirst and hunger, degree of satisfaction, the time required for Modified Post Anesthetic Discharge Scoring System scale, first urination time, electrolyte level (sodium, potassium, and calcium), and blood glucose level were also determined. A total of 93 patients were recruited in this study. No significant difference was observed in the cross-sectional area (CSA) of the gastric antrum area at T0 between low- and high-dose groups (P = .912). There was a significant difference in CSA of gastric antrum at 120 minutes after oral intake between the low- and high-dose groups (P = .015). No significant difference was observed in the CSA of gastric antrum at 0 minutes and 120 minutes in the low-dose group (P = .177). In the high-dose group, the CSA of gastric antrum significantly differed at 0 minutes and 120 minutes (P < .001). There was a significant difference in the visual analog scale scores of thirst and hunger at 4 and 5 hours after bowel preparation among 3 groups (P = .001, P = .029, P < .001, P = .001). The degree of satisfaction in low- and high-dose groups was significantly higher than that in the control group (both P < .001). In conclusion, it is feasible and safe to deliver an oral intake of 5 mL/kg carbohydrate-rich drink 2 hours before painless colonoscopy. The comfort level and degree of satisfaction of patients can be further improved.

Mycobacterium tuberculosis Rv3435c regulates inflammatory cytokines and promotes the intracellular survival of recombinant Mycobacteria.

Mycobacterium tuberculosis is a pathogenic bacterium that is parasitic in macrophages and show high adaptation to the host's immune response. It can also trigger a complex immune response in the host. This relies on proteins encoded by a series of M. tuberculosis-encoded virulence genes. We found that the M. tuberculosis Rv3435c gene is highly conserved among pathogenic mycobacteria, and might be a virulence gene. To explore the gene function of Rv3435c, we used Mycobacterium smegmatis to construct a recombinant mycobacterium expressing Rv3435c heterologously. The results that Rv3435c is a cell wall-related protein that changes bacterial and colony morphology, inhibits the growth rate of recombinant mycobacteria, and enhances their resistance to various stresses. We also found that the fatty acid levels of the recombinant strain changed. Simultaneously, Rv3435c can inhibit the expression and secretion of inflammatory factors and host cell apoptosis, and enhance the survival of recombinant bacteria in macrophages. Experimental data indicated that Rv3435c might play an important role in Mycobacterium tuberculosis infection.

The effect of fibroblast growth factor 21 on a mouse model of bovine viral diarrhea.

Previously, we researched that bovine viral diarrhea virus (BVDV) induced a very significant increase in fibroblast growth factor 21 (FGF21) expression in mouse liver and that FGF21 was increased in the peripheral blood of BVD cattle and BVD mice. To determine the role of FGF21 in relieving clinical symptoms and inhibiting the intestinal damage caused by BVDV in BVD development in mice, BALB/c mice were intraperitoneally injected with cytopathic biotype (cp) BVDV-LS01 (isolated and identified by our group) to establish a BVD mouse model. The role of FGF21 in the BVD mouse model was investigated by injecting the mice with FGF21. The animals were divided into control, BVDV challenge, BVDV + FGF21, BVDV + FGF21Ab (anti-FGF21 antibody), and BVDV + IgG (immunoglobulin G) groups. The stool consistency, the degree of bloody diarrhea, histopathological changes, inflammatory cell infiltration, weight loss percentage, and detection of BVDV in the feces of the mice were examined, and the pathological changes and inflammatory cytokine expression were analyzed. The results showed that after BVDV challenge, the average BVD mouse model score of the BVDV mice was 11.6 points. In addition to mild diarrhea and tissue damage, BVDV was detected in the stools of 13 BVDV mice. Only two mice in the control group had scores (both, 1 point each). The comprehensive scoring results demonstrated the successful establishment of the BVD mouse model. FGF21 alleviated the clinical symptoms in the BVD mice and significantly improved weight loss. Furthermore, FGF21 inhibited the BVDV-induced leukocyte, platelet, and lymphocyte reduction while inhibiting the expression of BVDV-induced inflammatory factors. In the BVD mice, FGF21 promoted duodenal epithelial cell proliferation, thereby significantly improving the damage to the cells. In conclusion, FGF21 exerted a good therapeutic effect on the BVD mouse model.

Spectrum-Efficacy Relationships between GC-MS Fingerprints of Essential Oil from Valerianae Jatamansi Rhizoma et Radix and the Efficacy of Inhibiting Microglial Activation.

The bioactive ingredients of essential oil from Valerianae Jatamansi Rhizoma et Radix (the Rhizome et Radix from Valerianae Jatamansi Jones) (EOVJRR) on the efficacy of inhibiting microglial activation were investigated with the approach of spectrum-efficacy relationship. Fourteen batches of Valerianae Jatamansi Rhizoma et Radix were extracted and analyzed by gas chromatography-mass spectrometry (GC-MS), and their activities in the efficacy of inhibiting microglial activation were assayed by measuring the inflammatory responses induced by lipopolysaccharide (LPS) in microglia cells from mice. The spectrum-efficacy relationships between fingerprints and the efficacy of inhibiting microglial activation of EOVJRR were established by grey relational analysis (GRA). Twenty common peaks were obtained from the GC-MS fingerprints of EOVJRR. P12 (vetivenol), P1 (bornyl acetate), P5 (seychellene), and P3 (ß-elemene) indicated inhibition on microglia activation together, according to the spectrum-efficacy relationships. The current results established a general model for the spectrum-efficacy relationships of EOVJRR by GC-MS and the efficacy of inhibiting microglial activation, which could be applied to identify the bioactive ingredient and control the quality of herbs.

Application of Immune Checkpoint Inhibitors in the Treatment of Cholangiocarcinoma.

Cholangiocarcinoma is a general term for intrahepatic and extrahepatic malignant tumors deriving in the biliary system. According to the location, it is divided into intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma. Progressive cholangiocarcinoma yields poor outcomes with radiotherapy; therefore, there is an urgent need for new therapeutic breakthroughs. Immune checkpoint inhibitor (ICI) therapy brings the treatment for cancer into a new field, with the use of drugs targeting PD-1/PD-L1 and CTLA-4 considerably extending the survival of patients with melanoma, lung cancer, and other solid tumors. The FDA has approved the application of pembrolizumab for solid tumors with high microsatellite instability and defective mismatch repair, including cholangiocarcinoma. Moreover, the combination of ICIs with chemotherapy and radiation therapy showed good promise. The aim of the present study was to review the application of ICIs in the treatment of cholangiocarcinoma and to summarize the reported individualized immunotherapy-based protocols and ongoing clinical trials for clinical reference.

Prevalence of Bovine Tuberculosis in Yaks Between 1982 and 2020 in Mainland China: A Systematic Review and Meta-Analysis.

Bovine tuberculosis (bTB) is a major chronic bacterial disease in cattle and is the major economic and animal welfare issue in the world. Although the economic costs and public health safety risks associated with the disease are considerable, the overall epidemiology of the Chinese yak (Bos grunniens) bTB is unclear. To fully reveal the basic prevalence of yak bTB in different regions of China, we searched five databases including PubMed, Science Direct, CNKI (China National Knowledge Infrastructure), Wanfang and Chongqing VIP. Based on the incidence and prevalence of yak tuberculosis in China from 1982 to 2020, a meta-analysis of yak bTB in China was established for the first time. By formulating the search formula, 97 studies were searched in five databases. According to the established exclusion criteria and excluded comments and repeated and irrelevance research, we finally selected 19 cross-sectional studies, which showed the prevalence of bTB in Chinese yaks. Random-effect meta-regression model analysis showed that the estimated prevalence of 122,729 yaks in China was 1.0 (95% confidence interval [CI]: 0.0-1.0). The regional prevalence varies greatly, northwest China prevalence rate 0. 39% (95% CI: 0.2-0. 64) and southwest China prevalence rate 2.59% (95% CI: 1.94-3.34); in terms of province level, the prevalence was highest in Tibet 2.59% (95% CI: 1.94-3.34), followed by Xinjiang 2.36% (95% CI: 0.86-4.58), and Shanxi has the lowest 0.00% (95% CI: 0.00-0.98). This systematic review and meta-analysis identified the estimated prevalence of bTB in Chinese yaks and estimated the underlying factors associated with bTB, including geographic location, sampling year, age, and TB detection method. Provide evidence to plan corresponding disease control strategies for policymakers and to assess future economic risks accurately.

Prevalence and Risk Factors of Brucellosis, Chlamydiosis, and Bluetongue Among Sika Deer in Jilin Province in China.

Brucellosis and chlamydiosis are important zoonotic diseases and bluetongue virus (BTV) is an arthropod-borne viral disease of ruminants. They are widely distributed around the world, cause large economic losses, and significant harmful effects on humans. However, epidemiological information relating to transmission from commercial sika deer in China is limited. Therefore, from 2016 to 2017, 458 sika deer blood samples were collected from three cities in Jilin Province in China. The Brucella antigen and specific antibodies to Chlamydia and BTV were examined using RT-PCR, indirect hemagglutination assay, and ELISA, respectively. The prevalence of Brucella was found to be 12.9% (59/458) and the seroprevalence of Chlamydia and BTV was 14.4% (66/458) and 17.0% (78/458), respectively. Seasonality was considered a risk factor for the presence of Brucella or BTV in sika deer and the region was considered a risk factor for Chlamydia infection. These data provides reference values for both further research and disease control.

[Advance in studies on pharmacokinetics of baicalin].

Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin in vivo at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.

Anti-hepatitis B virus effects of dehydrocheilanthifoline from Corydalis saxicola.

In this report, the anti-hepatitis B virus (HBV) activity of dehydrocheilanthifoline (DHCH), a quaternary ammonium alkaloid isolated from the traditional Chinese medicine Corydalis saxicola Bunting (Papaveraceae), was determined in vitro. Following six days of treatment, DHCH efficiently suppressed the secretions of HBsAg and HBeAg in HepG2.2.15 cell cultures, with a half-maximal inhibitory concentration (IC(50)) of 15.84 and 17.12 µM, and with a therapeutic index (TI) of 7.32 and 6.77, respectively. Further studies revealed that DHCH reduced the levels of extracellular DNA, intracellular DNA and covalently closed circular DNA (cccDNA) of HBV in a dose-dependent and time-dependent manner, with IC(50) values of 15.08, 7.62 and 8.25 µM, respectively after six days of treatment. In contrast, the level of viral pre-genomic RNA (pgRNA) increased 6.13-fold after treatment with DHCH. Together, it was demonstrated for the first time that DHCH could significantly inhibit the replication of HBV, which warrants further studies on the antiviral mechanisms of DHCH, and suggests that it may be a promising candidate in the therapy of HBV infection.

BJ-B11, a novel Hsp90 inhibitor, induces apoptosis in human chronic myeloid leukemia K562 cells through the mitochondria-dependent pathway.

In the past few years heat shock protein 90 (Hsp90) inhibitors have been reported to possess significant antitumor activity. We investigated, for the first time, the antitumor activity of a novel Hsp90 inhibitor 2-(4-acetyloxycyclohexylamino)-4-(3, 6, 6-trimethyl-4-oxo-4, 5, 6, 7-tetrahydro-1H-indazol-1-yl)-benzamide (BJ-B11) and the molecular mechanism underlying the apoptosis it induces in human chronic myeloid leukemia K562 cells. The results revealed that BJ-B11 triggered growth inhibition in K562 cells and other malignant cell lines in vitro with only minor toxicity in a normal human cell line. BJ-B11 inhibited the proliferation of K562 cells in a concentration- and time-dependent manner, with IC(50) values of 1.1 ± 0.2 µM and 0.4 ± 0.1 µM after 48 and 72 h incubations respectively. This most likely results from cell cycle arrest at the G(0)/G(1) phase and the induction of apoptosis. In addition, BJ-B11 degraded the Hsp90 client proteins Bcr-Abl and Akt, induced activation of caspase-9 and caspase-3, and subsequent cleavage of PARP. The caspase signals may originate from mitochondrial dysfunction, which is supported by the finding of cytochrome c release. In addition, inactivation of the Akt signaling pathway may be involved in the process of BJ-B11-induced apoptosis. Taken together, our data provide a putative molecular mechanism for the anticancer effect of BJ-B11 on K562 cells, and suggest a potential application for BJ-B11 in chronic myeloid leukemia therapy.

Pentagalloylglucose downregulates cofilin1 and inhibits HSV-1 infection.

To investigate the anti-herpesvirus mechanism of pentagalloylglucose (PGG), we compared the proteomic changes between herpes simplex virus type 1 (HSV-1) infected MRC-5 cells with or without PGG-treatment, and between non-infected MRC-5 cells with or without PGG-treatment by 2-DE and MS-based analysis. Differentially expressed cellular proteins were mainly involved with actin cytoskeleton regulation. Significantly, PGG can down-regulate cofilin1, a key regulator of actin cytoskeleton dynamics. PGG can inhibit HSV-1-induced rearrangements of actin cytoskeleton which is important for infectivity. Furthermore, cofilin1 knockdown by siRNA also inhibited the HSV-1-induced actin-skeleton rearrangements. Both PGG-treatment and cofilin1 knockdown can reduce HSV-1 DNA, mRNA, protein synthesis and virus yields. Altogether, the results suggested that down-regulating cofilin1 plays a role in PGG inhibiting HSV-1 infection. PGG may be a promising anti-herpesvirus agent for drug development.