Objective To analyze the adverse reaction reports （ADRs） of drug-induced liver injury in recent ten years, explore the characteristics and related rules of drug-induced liver injury, and provide reference for clinical safe drug use. Methods ADRs in our hospital from 2011 to 2021 which belonged to drug-induced liver injuries were collected, and Pareto analysis was carried on. Results In 259 ADR reports, the most common type of drug-induced liver injury was hepatocellular injury （37.84%）. The age of drug-induced liver injury was mainly over 46 years, totaling 195 （75.28%）. Drugs were mainly distributed in cardiovascular system medicine （44.02%）, anti-infective medicine （23.94%）and anti-tumor medicine （11.58%）. Among the cardiovascular drugs, atorvastatin calcium 40mg and over 40mg were the highest proportion, with 53 cases （46.49%）. The main anti-infectious drugs were cephalosporins （29.03%）, carbapenem （19.35%）， antifungal （17.74%）and quinolones （11.29%）. Adverse reactions occurred within 6 days （69.88%）, the duration of adverse reactions was 1-2 weeks （31.66%）, and most patients were improved （47.88%） or cured （37.07%）. Conclusion For middle-aged and elderly patients, when the application of cardiovascular system drugs, anti-infective drugs or anti-tumor drugs, it is necessary to monitor the liver function changes of patients for at least 6 days. If there are abnormalities, the drugs should be stopped or given treatment in time, to avoid the progress of drug-induced liver injury.

OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation （STC） by regulating acid-sensitive ion channel 3 （ASIC3）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate. The successfully modeled rats were randomly divided into model group， Shaoyao gancao decoction group （1.5 g/mL）， lactulose group （208.4 mg/mL， positive control）， and combined inhibition group （Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg）， with 12 rats in each group. Additionally， 12 healthy rats were selected as the blank group. They were given relevant medicine once a day and continuously intervened for 14 days. After intervention， the intestinal propulsion function and visceral sensitivity of the model rats were detected. The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining. mRNA expressions of ASIC3， ERK1 and ERK2 as well as protein expressions of ASIC3， ERK1/2 and phosphorylated ERK1/2 （p-ERK1/2） in colon tissue of rats were detected； the ultrastructural changes of the enteric nervous system （ENS） -interstitial cell of Cajal （ICC）-smooth muscle cell （SMC） network in the rat colon were observed under electron microscopy. RESULTS Compared with the model group， the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased， while the visceral pain threshold was significantly decreased. The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased. The relative mRNA expression levels of ERK1， ERK2， and ASIC3， as well as the relative protein expression levels of p-ERK1/2 and ASIC3， and the p-ERK1/2 to ERK1/2 in the colonic tissue， were all significantly increased （P＜0.05 or P＜0.01）. Additionally， there was marked repair of the morphological structure of ICC and SMC， with closer gap junctions observed. Compared with the Shaoyao gancao decoction group， the combined inhibition group exhibited a diminished improvement in intestinal motility of rats， with statistically significant differences in the levels of some indicators （P＜0.05 or P＜0.01）； the repairing of the morphological structure of ICC and SMC was notably attenuated. CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats， and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway， thus promoting intestinal motility and reducing visceral sensitivity.

Objective To study the mechanism of Yangjing Zhongyu Decoction in regulating the initiation of primordial follicles in model rats with diminished ovarian reserve(DOR)based on lncRNA.Methods Three-day-old female rats were selected and their ovaries were cultured in vitro.The blank group,model group,DHEA group and Yangjing Zhongyu Decoction high-,medium-and low-dosage groups were set.The DOR model was induced by triptolide,corresponding drug containing serum was given to culture respectively.HE staining was used to observe germ cells and follicles,Western blot was used for determining the expressions of AMH,BMP15,PTEN,MST,TGF-β1,p-Smad1 protein,RT-PCR was used to detected AMH,BMP15,PTEN,MST,LTCONS-00011173,TGF-β1,Smad1 mRNA expression.Results Compared with the blank group,the number of primordial and growing follicles in the model group rats decreased(P<0.05),the expression of AMH,BMP15,TGF-β1,p-Smad1 protein in ovarian tissue decreased(P<0.05),expressions of PTEN and MST proteins increased(P<0.05),AMH,BMP15,TGF-β1,Smad1 mRNA expression decreased(P<0.05),while the expressions of PTEN,MST,and LTCONS-00011173 mRNA increased(P<0.05).Compared with the model group,the DHEA group and Yangjing Zhongyu Decoction high-and medium-dosage groups showed an increase in the number of primordial and growing follicles(P<0.05),the expressions of AMH,BMP15,TGF-β1 and p-Smad1 protein in ovarian tissue increased(P<0.05),PTEN and MST protein expressions decreased(P<0.05),AMH,BMP15,TGF-β1,Smad1 mRNA expressions increased(P<0.05),while PTEN,MST,and LTCONS-00011173 mRNA expressions decreased(P<0.05).Conclusion Yangjing Zhongyu Decoction may mediate TGF-β1/Smad1 signaling pathway through LTCONS-00011173,regulating primordial follicle initiation in DOR model rats.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Objective To investigate the anti-estrogenic activity of bisphenol A and its substitutes, and to analyze the relevant mechanisms. Methods Bisphenol A and its three most widely used substitutes (bisphenol S, bisphenol F and bisphenol AF) were selected as the docking ligand molecules, and estradiol was used as the control ligand molecule. The ligand molecules docking was simulated with estrogen receptor (ER) α and ERβ using AutoDock software. Results Bisphenol A forms a hydrogen bond with ERα at the His474 residue and with ERβ via three hydrogen bonds at Leu260, His428, and Asn431 residues. Similar to bisphenol A, bisphenol S, bisphenol F, bisphenol AF and estradiol primarily interact with ERα and ERβ through hydrophobic interactions and hydrogen bonds, but with varying optimal binding sites and affinities. The binding forces of the optimal binding sites for bisphenol A, bisphenol F, bisphenol AF, bisphenol S and estradiol with ERα were -4.15, -4.19, -2.73, -4.62 and -5.37 kcal/mol, respectively, and with ERβ were -3.76, -3.91, -2.86, -3.93, and -4.98 kcal/mol, respectively. The affinity ranking for two ERs with these five molecules from high to low was estradiol > bisphenol S> bisphenol F> bisphenol A > bisphenol AF. Conclusion The affinity between bisphenol compounds with ERα and ERβ is mainly based on the hydrophobic interaction with non-polar residues of the receptor and hydrogen bonding with key residues. Bisphenol S, bisphenol F and bisphenol AF showed similar or even stronger endocrine disrupting effects than bisphenol A.

As a severe clinical manifestation of nonalcoholic fatty liver disease， nonalcoholic steatohepatitis （NASH） is characterized by lipid deposition and inflammatory damage in the liver. At present， clinical medications for NASH are still in the exploratory phase， and it is urgent to make progress. Recent studies have shown that the pathogenesis of NASH is associated with circadian rhythm disorders in the liver， with the specific manifestation of dysregulated expression of liver clock genes such as BMAL1， which increases hepatic lipogenesis， reduces fatty acid oxidation， and activates pro-inflammatory factors. Therefore， improving circadian rhythm of the liver and regulating the expression of liver clock genes are feasible strategies for the prevention and treatment of NASH. Currently， some medications for NASH via activating the proteins encoded by clock genes have been applied in animal experiments， for example， the REVERB full-agonist SR9009 can inhibit the development of liver inflammation， which confirms the possibility of NASH treatment by targeting the proteins encoded by clock genes. This article summarizes the role of hepatic clock genes in regulating lipid metabolism and the development and progression of inflammation in the liver and elaborates on the recent advances in medications targeting clock genes and the proteins encoded by clock genes， in order to provide new targets for the treatment of NASH.

Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Objective To analyze the medication law of core prescriptions and categorized prescriptions of TCM for the treatment of heart failure with preserved ejection fraction(HFpEF);To provide references for clinical prescriptions of HFpEF.Methods The clinical research literature on TCM for HFpEF was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from establishment of the databases to November 1,2023.Data mining methods,such as complex network,prescription similarity network and community detection method were used to explore the prescription medication law of HFpEF.Results Totally 142 articles related to TCM treatment of HFpEF were included,containing 146 prescriptions and involving 162 kinds of Chinese materia medica.The most frequently used drugs were represented by Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma and Poria.The core prescription and the commonly used modified law of HFpEF treatment were obtained by complex network analysis.The core prescription consisted of Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Cinnamomi Ramulus,Descurainiae Semen Lepidii Semen,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Rubra,Ophiopogonis Radix and Angelicae Sinensis Radix.Further based on the prescription similarity network and community detection method,the basic prescriptions of the 3 major community of categorized prescription corresponding to the HFpEF staging and syndrome types were obtained,and the staged diagnosis and treatment medication law with the development of the HFpEF disease course were found.Conclusion Invigorating qi and activating blood circulation,warming yang and promoting diuresis are the main therapeutic principles of HFpEF.Data mining technology provides a feasible method for the analysis of core prescriptions and categorized prescriptions for HFpEF,which can provide a basis for the diagnosis and treatment law and medication experience of HFpEF in TCM.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

A 9-year-old girl presented with a symptomless irregular dark brown papule on the vulva for 2 weeks. The patient was initially clinically diagnosed with pigmented nevus, and underwent surgical excision. Postoperative histopathological examination showed dilated glands and tubules in the dermis, eosinophilic secretions and pigment granules in the tubules, decapitation secretion in the inner layer cells, and flat myoepithelial cells around the tubules; a large amount of brown-black pigments were seen in the glands, tubular epithelium and interstitium, and lymphocytes and plasma cells infiltrated the interstitium. Finally, the diagnosis of pigmented apocrine hamartoma was made.