Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Rudimentary horn pregnancy: clinical analysis of 12 cases and literature review / 中华妇产科杂志

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Threatened Abortion / 中国实验方剂学杂志

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Photoelectric therapy for rosacea / 中华皮肤科杂志

Rosacea is a chronic inflammatory dermatosis mostly occurring on the central face, and its pathogenesis is still unclear. Currently, drug treatment is the first-line therapy for rosacea. In recent years, photoelectric therapy has showed a favorable therapeutic effect on rosacea by selective photothermolysis. This review summarizes latest advances in photoelectric therapy for rosacea.

A case of mitochondrial diabetes mellitus complicated with hypopituitarism and literature review / 中华内分泌代谢杂志

The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.

Relationship between ALDH2 rs671 gene polymorphism and body fat content in Han population / 中华健康管理学杂志

Objective:To investigate the relationship between ALDH2 rs671 gene polymorphism and body fat content in Chinese Han population.Methods:It was a cross-sectional study. A total of 3 943 Chinese Han people were selected for physical examination in the Department of Health Medicine in the Second Medical Center of Chinese PLA General Hospital from January 2017 to January 2020, including 2 749 males and 1 194 females; the average age was (48.12±7.98) years. The research subjects were divided into obesity group and non-obesity group according to their body fat rate. The basic information including age, gender, disease history, height, weight, body fat content and blood samples were collected; the ALDH2 rs671 gene polymorphism was detected. Genotype and allele frequencies were compared between groups by using χ2 test. The comparison of clinical data between different genotypes was conducted by using one-way analysis of variance. The correlation between various indicators, lifestyle and genotype was analyzed by using a logistic regression model. Results:The distribution of ALDH2 rs671 genotype was wild genotype GG (68.6%), heterozygous mutant genotype GL (28.7%) and homozygous mutant genotype LL (2.7%). In terms of baseline characteristics, there were significant differences in male (67.5% vs 71.3%), body mass index (BMI, (23.12±2.64) kg/m 2 vs (27.10±2.75) kg/m 2), genotype distribution (GG 65.6% vs 70.6%), drinking history (64.4% vs 68.8%), history of hypertension (18.7% vs 36.9%), coronary heart disease (3.7% vs 5.6%) and diabetes (9.7% vs 15.0%) between the obesity and non-obesity group (all P<0.05). Multifactor logistic regression showed that ALDH2-GG genotype ( OR=1.386, 95% CI: 1.078-1.782), age ( OR=1.051, 95% CI: 1.035-1.068), and BMI ( OR=2.182, 95% CI: 2.043-2.331) were risk factors for obesity differentiated by body fat percentage, and male ( OR=0.175, 95% CI: 0.123-0.250) was protective factor (all, P<0.05). Conclusion:ALDH2 rs671 polymorphism is related to body fat content. The risk of excessive body fat content in individuals with GG genotype is significantly increased.

Correlation between serum non-high density lipoprotein cholesterol and bone mass levels in different body parts in physical examination population / 中华健康管理学杂志

Objective:To compare the relationship between non-high-density lipoprotein cholesterol (non-HDL-C) and bone mass in different body parts in the physical examination population.Methods:It was a cross-sectional study. The data of 595 physical examiners who visited the Institute of Health Management, PLA General Hospital from June to September 2016 were retrospectively analyzed. The bone mass levels of lumbar 1-4 vertebral body (spine) and femur, average bone density were measured by double light energy X-ray bone density instrument. The basic information and biochemical indices of the physical examiners were collected. The difference between blood lipid components (including Non-HDL-C) and bone mass level of each body part were analyzed.Results:According to blood lipid stratification, there were significant differences in spine T value (T-spine) between triglyceride (TG) groups (-0.15±1.41 vs -0.38±1.3), Non-HDL-C groups (-1.01±0.74 vs -1.21±0.59, -1.04±0.73 vs -1.30±0.45,-1.07±0.71 vs -1.30±0.26) and low-density lipoprotein cholesterol (LDL-C) groups (-1.01±0.71 vs -1.32±0.56)(all P<0.05). There was no statistically significant difference in other lipid groups and femoral T values in each component′s blood lipids. The T-spine decreased significantly in the LDL-C≥3.4 mmol/L group, and the differences were all significant among the Non-HDL-C group (all P<0.05). In binary logistic regression analysis, LDL-C≥3.4 mmol/L ( OR=3.961,95% CI:1.310-11.974) and Non-HDL-C>4.1 mmol/L ( OR=3.600,95% CI:1.035-12.524) were risk factors for vertebral bone mass loss (both P<0.05). Conclusion:People with elevated serum TG, Non-HDL-C and LDL-C in the physical examination population are prone to bone abnormalities. Non-HDL-C≥4.1 mmol/L and LDL-C≥3.4 mmol/L are more closely related to the vertebral bone mass loss and are the risk factors for vertebral bone mass loss.

Discussion on application of control level of radioactive contamination on personnel′s body surface in a nuclear and radiological emergency / 中华放射医学与防护杂志

There are differences and inconsistencies to some degree in the radioactive contamination control level of personnel′s body surface availiable in many national standards, thus puzzling the users. Therefore, it is proposed to compare the applicable scope, conditions and differences between relevant national standards, and combine with similar clinical nuclear medicine standards of radiological protection content to presevent recommendations on the contamination control level that should be correctly applied in an event of nuclear and radiological emergency. Based on the discussion of similar standards, the contaminated personnel with α of 0.04-10 Bq/cm 2 and β of 0.4-100 Bq/cm 2 are advised to be treated in the institutions with higher than secondary medical insititution. Both α econtamination control levels less than 0.04 Bq/cm 2 and β levels less than 0.4 Bq/cm 2 could be achivable, if fully decontaminated.

Research progress of epigallocatechin gallate in radiation protection / 中国辐射卫生

Epigallocatechin gallate (EGCG) is a major polyphenol component in green tea. EGCG has high free radical scavenging activity, radiation protection efficiency, and metal-chelating capacity due to its unique structure with hydroxyl groups. EGCG and its derivatives have been reported in various fields. This paper reviews the effects of EGCG, including radiation protection, heavy metal ion adsorption, and promotion of heavy metal ion excretion. EGCG has the potential to be used as an ideal radiation protection agent, heavy metal adsorbent, and even excretion promoting agent.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Effects of Methionine Restriction on Proliferation, Cell Cycle, and Apoptosis of Human Acute Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells.@*METHODS@#Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay.@*RESULTS@#Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase (P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 (P < 0.05), CDC2 (P < 0.01) and Bcl-2 (P < 0.001) in HL-60 and Jurkat cells.@*CONCLUSION@#Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.

Quantitative assessment of choriocapillaris perfusion in patients with diabetic retinopathy using ultra-high-speed swept source optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the characteristics of choriocapillary blood flow in different patients with diabetic retinopathy(DR)based on the measurement of choriocapillaris(CC)perfusion density(PFD)using ultra-high-speed swept-source optical coherence tomography angiography(SS-OCTA)METHODS: The cross-sectional observational study was conducted on 139 cases(139 eyes)who admitted to the Second People's Hospital of Hefei, including 115 DR cases(115 eyes)and 24 control cases(24 eyes). The color retinal images were graded according to the Early Treatment Diabetic Retinopathy Study(ETDRS)scale, and the DR eyes were classified into non-DR group, nonproliferative diabetic retinopathy(NPDR)group, NPDR combined with diabetic macular edema(DME)group and proliferative diabetic retinopathy(PDR)group. The ultra-high-speed SS-OCTA was used to scan a 3mm×3mm region centered on the macular central fovea, the CC perfusion area was measured by the built-in software, and PFD was calculated. Multivariable linear regressions were used to evaluate the correlation between PFD of CC and DR degree.RESULTS: The degree of DR had a correlation with blood perfusion of CC after adjusting for various confounding factors. When compared to the control group, the PFD of CC in the central fovea of the NPDR group decreased by 9.358 units(95%CI -18.484～-0.232, P=0.045)and 9.284 units in the paracentral fovea(95%CI -18.487～-0.090, P=0.048); In the NPDR combined with DME group, the central fovea CC PFD decreased by 18.173 units(95%CI -28.583～-7.762, P=0.001), while the paracentral fovea decreased by 17.032 units(95%CI -27.521～-6.544, P=0.002); In the PDR group, the central fovea CC PFD decreased by 28.309 units(95%CI -39.978～-16.640, P&#x003C;0.001), while the paracentral fovea decreased by 25.841 units(95%CI -37.597～-14.085, P&#x003C;0.001).CONCLUSION: The macular perfusion can be objectively quantified by the measurement of CC PFD with ultra-high-speed SS-OCTA. The CC PFD in the macular region was significantly reduced in more advanced stages of DR. Furthermore, future research should focus on longitudinal studies in the causal relationship between CC perfusion and DR progression.

Vitreous properties in patients with diabetes mellitus and its relationship with proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

When it comes to diabetic patients, persistent hyperglycemia and associated pathological conditions will not only cause diabetic retinopathy(DR)but also have an impact on the metabolism of vitreous, leading to diabetic vitreopathy. Owing to the adjacent anatomical position between the vitreous and retina, diabetic vitreopathy and DR are mutually promoted. Changes in vitreoretinal interface such as posterior vitreous detachment(PVD)and vitreoschisis, provide a scaffold for fibrovascular proliferative membrane and are closely associated with pars plana vitrectomy(PPV). This article sorts out the variation of diabetic patients' vitreous structure and biochemical components, along with the changes in the vitreous-retinal interface, particularly for the related research on its relationship with proliferative diabetic retinopathy(PDR), aiming at providing further cognition of diabetic vitreopathy as well as references for DR treatment and formulation of PPV.

Efficacy of hepatic arterial infusion chemotherapy and its multimodality therapeutic regimens in treatment of patients with advanced hepatocellular carcinoma and related prognostic factors / 临床肝胆病杂志

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

Effect and mechanism of gerbeloid J from Gerbera piloselloides (L.) Cass. on cycle and apoptosis of breast cancer cells / 药学学报

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.

Technique optimization of intravenous or intraperitoneal injection of Evans blue combined with retinal preparations in mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.

GPRC5B protects osteoarthritis by regulation of autophagy signaling

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish / 南方医科大学学报

OBJECTIVE@#To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder.@*METHODS@#Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated.@*RESULTS@#Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05).@*CONCLUSION@#Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.

Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad / 中华肝脏病杂志

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.