Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

OBJECTIVE To study the therapeutic effect of saikosaponins and paeoniflorin on rats with premenstrual dysphoric disorder(PMDD) model of liver Qi depression and the effect on neurotransmitters in hippocampal brain area. METHODS The PMDD rat model of liver Qi depression was prepared by the time-chosen chronic restraint stress method, and the depressive symptoms of rats were evaluated by the intervention of saikosaponins and paeoniflorin, the open field experiment and forced swimming experiment, and the changes of neurotransmitter levels in the hippocampal brain region of rats were detected by UHPLC-MS/MS target metabolomics. RESULTS The levels of 5-HT, Glu, GABA and NE in the hippocampal brain area of PMDD rats were significantly increased, and the levels of 5-HT, Glu, GABA, NE, DA and E were not statistically significant from those of the normal group after the intervention of saikosaponins and paeoniflorin. CONCLUSION Saikosaponins and paeoniflorin alleviates depression in rats with PMDD by regulating neurotransmitter levels, and it may be the pathway for the clinical treatment of PMDD with liver qi depression in the formulations of Bupleuri Radix and Paeoniae Radix Alba.

With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.

Diesel exhaust (DE), Group 1 carcinogen, is an important source of air pollutants. Studies show that DE exposure associates with elevated incidences of respiratory and cardiovascular diseases. The toxic effects of DE are closely related to its components. Polycyclic aromatic hydrocarbons (PAHs) are one of the main toxic components in DE and are often used as human exposure biomarkers to DE. However, the exposure assessment of DE using PAHs as biomarkers could be interfered due to the other sources of PAHs. Therefore, identification of highly specific and reliable PAHs sourced biomarkers of DE exposure has become a hotspot of current research. New biomarkers of DE may play an important role in determining human exposure to DE and establishing dose-response relationship of DE exposure and health outcomes of interest. This paper focused on current progress in terms of PAHs sourced biomarkers of human exposure to DE with the following aims: (1) to clarify the types of PAHs sourced biomarkers to DE; (2) to explore the applicability and limitations of PAHs sourced biomarkers for DE exposure assessment in occupational exposure and environmental exposure analysis; and (3) to summarize the analysis methods for PAHs sourced exposure biomarkers in human urine samples and compare the advantages and disadvantages of different analytical methods.

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

Objective: To propose reasonable suggestions to promote the standardization of clinical studies by reviewing the systematic reviews and meta-analyses of acupuncture-moxibustion treatment of essential hypertension (EH). Methods: Computer retrieval was conducted through Excerpta Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure (CNKI), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), and Wanfang Academic Journal Full-text Database (Wanfang) to collect systematic reviews and meta-analyses relevant to treating EH with acupuncture-moxibustion therapy. The time range was from the database's inception till July, 2020. The studies were screened based on the inclusion and exclusion criteria and then data-extracted. The study's quality and evidence ratings were performed by referring to the preferred reporting items for systematic review and meta-analysis (PRISMA), a measurement tool to assess systematic reviews 2 (AMSTAR 2), and the grading of recommendations, assessment, development, and evaluation (GRADE). Results: A total of 14 studies, 10 in Chinese and 4 in English, published between 2012 and 2019, were included, involving 70 outcome measures. The methodological quality was rated as critically low, the reporting was relatively complete or had certain flaws, and the evidence strength was rated as low or very low. Conclusion: Regarding the acupuncture-moxibustion treatment of EH, the methodological quality and outcome measure evidence of existing systematic reviews and meta-analyses are relatively low, and the reporting quality also expects further improvements.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Abstract: Objective To compare the diagnostic efficacy of the upgraded version of the GeneXpert automated fluorescent quantitative PCR system (GeneXpert MTB/RIF Ultra, GeneXpert Ultra) and the original version of the GeneXpert system (GeneXpert MTB/RIF, Xpert), real-time fluorescent quantitative nucleic acid detection (FQ-PCR), real-time fluorescent thermostatic amplification of Mycobacterium tuberculosis RNA (SAT-RNA), real-time fluorescent thermostatic amplification detection of DNA (thermostatic amplification method) and traditional BACTEC MGIT 960 liquid culture (culture method) for special specimens of tuberculosis, in order to analyze its application value in clinical detection. Methods Using prospective research methods, a total of 170 special specimens (including 47 pleural and ascites effusion samples, and 34 24-hour urinary sediment specimens, 49 tissue specimens and 40 fester specimens) were collected i'an Chest Hospital from January to September 2021. GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were used for detection. Clinical diagnosis was used as the standard, and sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate, and Kappa value were compared among the methods. Results The sensitivities of GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were 65.18% (73/112), 49.11% (55/112), 37.50% (42/112), 19.64% (22/112), 8.04% (9/112), and 22.32% (25/112), respectively. The sensitivity of GeneXpert Ultra was higher than that of the other five methods, and the differences were statistically significant (χ2=66.25, 42.10, 28.89, 13.09, 4.92, 15.18, all P<0.05). GeneXpert Ultra result analysis showed that: 5.48%(4/73) cases had trace, that is, trace Mycobacterium tuberculosis load, 79.45% (58/73) cases were extremely low, 10.96% (8/73) cases were low, 2.74% (2/73) were medium, , and 1.36% (1/73) were high load. In 4 trace samples, the Xpert detection was negative for all. Of the 73 GeneXpert Ultra positive reports, 63 were rifampicin-sensitive, 6 were rifampicin-resistant, and 4 were rifampicin-resistant but of unclear resistance. Of the 55 Xpert positive reports, 45 were rifampicin-sensitive, 2 were rifampicin-resistant, and 8 were rifampicinresistant but of unclear resistance.. Conclusions The new generation of GeneXpert MTB/RIF Ultra has high sensitivity, specificity and drug resistance detection rate, and its advantage is even more apparent in the pathogenic diagnosis of special specimens of tuberculosis. It can be used as one of the preferred methods in samples with low bacterial load.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy* ; Humans ; SARS-CoV-2 ; Treatment Outcome

Objective:To investigate the correlation between nutritional status and nosocomial infection in elderly patients with acute leukemia.Methods:A total of 202 elderly patients with acute leukemia hospitalized in the Department of Hematology of the First Affiliated Hospital of Anhui Medical University from June 2015 to December 2017 were randomly included as research objects.The nutritional status of patients was assessed by the Patient-Generated Subjective Global Assessment(PG-SGA), and the blood routine and biochemical indexes were compared among patients with different nutritional conditions.The correlations between clinical characteristics and PG-SGA score and between nutritional status and nosocomial infection were analyzed.Univariate analysis and multivariate Logistic regression analysis were used to evaluate the related factors for the nosocomial infection.Results:The hemoglobin and albumin were higher in patients with PG-SGA score of 0-8[(97.02±2.86)g/L and (39.78±0.50)g/L, respectively]than in patients with PG-SGA score ≥ 9[(83.02±3.28)g/L and (37.71±0.71)g/L]( P=0.003, 0.016). And C-reactive protein(CRP)was lower in patients with PG-SGA score of 0-8[(33.98±5.34)mg/L]than in patients with PG-SGA score ≥ 9[(58.82±8.36)mg/L]( P=0.015). There were significant differences in PG-SGA scores among patients with different age, disease stage, disease type and gastrointestinal reaction( t=-6.562, 3.292, 2.869 and 2.268, P=0.000, 0.001, 0.006 and 0.041). The PG-SGA score was positively correlated with the incidence of nosocomial infection( r=0.544, P=0.000). Logistic regression analysis showed that PG-SGA score was an independent risk factor( OR=2.11, 95% CI: 1.66-2.71, P=0.000). And albumin was a protective factor( OR=0.86, 95% CI: 0.77-0.93, P=0.000)for the nosocomial infection in elderly patients with acute leukemia. Conclusions:The nutritional status is closely related to the occurrence of nosocomial infection in elderly patients with acute leukemia.Elderly acute leukemia patients with malnutrition should be given adequate nutritional support as soon as possible to improve their nutritional status and improve prognosis.