This study investigates whether compounds in Salvia miltiorrhiza Bunge can bind to the Toll like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) protein complex and exhibit anti-inflammatory activity. Virtual screening of reported chemical components of Salvia miltiorrhiza Bunge against TLR4/MD2 was conducted in this study. The selected compound, neoprzewaquinone A (Neo A), was tested for its impact on the binding of lipopolysaccharide (LPS) to receptors on the cell membrane, its affinity for the protein, its influence on the dimerization of TLR4 and MD2 in LPS-induced cells, and its effects on the phosphorylation of nuclear factor-κB (NF-κB) p65 protein and the secretion of inflammatory cytokines in cells. Results indicate that Neo A in Salvia miltiorrhiza Bunge exhibited the highest virtual binding affinity with TLR4/MD2, with a value of -12.8 kcal·mol^-1. Neo A significantly inhibited the binding of LPS to receptors on the cell membrane (P < 0.01). Moreover, Neo A demonstrated affinity for rhTLR4/MD2, rhTLR4, and rhMD2, with K_D values of 267, 534, and 228 nmol·L^-1, respectively. Amino acid residues like TYR131 and PHE121 in TLR4/MD2 might play a role in the alkyl and π-alkyl hydrophobic interactions with Neo A. Neo A also significantly inhibited the dimerization of TLR4 and MD2 in LPS-mediated cells (P < 0.01) and markedly suppressed the phosphorylation of NF-κBp65 protein (P < 0.05). Furthermore, Neo A significantly or markedly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced cells (P < 0.05, P < 0.01). In conclusion, Neo A exerts its anti-inflammatory effects by binding TLR4/MD2 then disrupting the binding of LPS to TLR4/MD2. It may serve as a TLR4/MD2 inhibitor with the potential to treat inflammation-related diseases targeting TLR4/MD2.

Ubiquitin-specific protease 1 (USP1) is one of the deubiquitinating enzymes which has received increasing attention in cancer research. USP1 is overexpressed in many types of cancer cells, and has been found to control tumorigenesis and progression by regulating various proteins associated with tumors, such as SIK2, GSK-3β, and Bcl-2. Knockdown or pharmacological inhibition of USP1 can effectively suppress tumors and is also expected to address the issues of cisplatin and poly ADP-ribose polymerase (PARP) inhibitor resistance. This review describes the structure and function of USP1 and the relationship between USP1 targets and tumors and systematically summarizes the structure-activity relationships of small molecule USP1 inhibitors disclosed from 2013 to 2023. Finally, this review discusses the challenges and opportunities in developing small molecule USP1 inhibitors.

Based on the species-specific peptides of Pheretima and its common counterfeit (Metaphire magna), an identification method was established using ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) for quality evaluation of Pheretima and its preparations. Separation was performed on a CORTECS T3 C18 column with 0.1% formic acid and acetonitrile as the mobile phases. Mass spectrometry with multiple reaction monitoring (MRM) using ESI⁺ mode was used to simultaneously monitor three ion pairs. The results indicated that the method was specific and could distinguish Guang Dilong, Hu Dilong, and M. magna, which were consistent with those of DNA barcode identification. The adulteration test showed that the LOD of peptide M was 1 μg·g^-1. Peptide M could be detected when 1% M. magna was added to Guang Dilong, indicating the high sensitivity of the method. Fifty-four batches of commercially available samples contained 35% Guang Dilong, 35% Hu Dilong, and 15% M. magna. No ions were detected in 15% of the samples, and DNA barcode identification revealed that they were mainly from Amynthas, with similar appearance to Hu Dilong. The analysis results of the formulation showed that no peptide ions were detected in 3 batches of Xiaohuoluo pills (3/6) and M. magna were detected in 2 batches of Shenjindan capsules (2/4). The developed method in the study has good specificity, sensitivity, and feasibility, and could be used for quality control of Pheretima and its related preparations. It is of great significance for improving quality standards and regulating the medicinal market of Pheretima.

A new cadinane-type sesquiterpenoid, pogocablene P (1), and a new natural product with cyclohexanone skeleton, pogocablone A (2), were isolated from the EtOAc soluble fraction of the aerial parts of Pogostemon cablin by several chromatographic methods, such as silica gel, Sephadex LH-20, ODS and high performance liquid chromatography (HPLC), and so on. Their structures were identified by means of mass spectrometry and nuclear magnetic resonance spectroscopy. In addition, the absolute configuration of compound 2 was determined by electronic circular dichroism (ECD) calculation. Furthermore, the anti-influenza virus and anti-inflammatory activities of compounds 1 and 2 were evaluated.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To investigate the clinical efficacy of a compound oral sulfate solution for preoperative bowel cleansing in colonic polyp patients.Methods Patients who underwent colonoscopic polypectomy were divided into control group and treatment group according to cohort method methods.Patients in the control group were given compound polyethylene glycol electrolyte powder.They started taking it 4-6 hours before colonoscopy and completed the 4 liters of solution within 2 hours.Patients in the treatment group were given a compound oral sulfate solution.They took 1.5 liters of the solution the evening before surgery and repeated the same dosage on the day of the operation.Intestinal cleanliness was assessed using the Boston bowel preparation scale(BBPS),bowel preparation compliance,drug tolerance,patient satisfaction,and incidence of adverse drug reactions were compared between the two groups.Results Control group and treatment group each consisted of 40 cases.The total BBPS scores for the control group and treatment group were(6.68±1.19)and(7.43±1.23)points,respectively.This difference was statistically significant(P＜0.01).Medication compliance rates in the control group and treatment group were 70.00％(28 cases/40 cases)and 95.00％(38 cases/40 cases),respectively;movement compliance rates were 67.50％(27 cases/40 cases)and 97.50％(39 cases/40 cases)in the two groups,while medication tolerance rates were 67.50％(27 cases/40 cases)and 90.00％(36 cases/40 cases);patient satisfaction with bowel preparation were(1.89±0.75)and(2.42±0.43)points for the control and treatment groups,respectively;statistically significant differences were found between the control and treatment groups in all the above indicators(P＜0.05,P＜0.01,P＜0.001).The main adverse drug reactions in the control and treatment groups were nausea and vomiting,with occurrence rates of 10.00％(4 cases/40 cases)and 5.00％(2 cases/40 cases),respectively.The comparison of adverse drug reactions occurrence rate between the two groups showed no statistically significant difference(P＞0.05).Conclusion Taking compound oral sulfate solution for intestinal preparation,the intestinal cleaning effect is better than that of compound polyethylene glycol electrolyte powder,and the patient's compliance and drug tolerance are higher,and the patient's satisfaction can be effectively improved.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

Objective lo investigate the protective effect of dihydromyricetin(DHM)against exercise-induced muscle damage(EIMD)in mice and its potential mechanism. Methods Adult male C57BL/6J mice were randomly divided into control group(CG),exercise group(EG),and exercise+100 mg/kg weightd DHM(DHM)group.The intervention lasted for four weeks,during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day.The day after the training,a 90-min treadmill exercise(slope:0 and speed:18 m/min)was conducted in both EG and DHM groups.Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise,followed by the measurement of serum creatine kinase(CK)and lactate dehydrogenase(LDH)activities,total superoxide dismutase(T-SOD)activity,malondialdehyde(MDA),and skeletal muscle mitochondrial enzyme complex Ⅰ and Ⅱ activities.Histological changes in the skeletal muscle were observed by transmission electron microscopy,and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG.The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention.Western blotting demonstrated that the expressions of sirtuin type 3(SIRT3),estrogen-related receptor alpha,and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. Conclusion DHM can relieve EIMD in mice,possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

Objective To investigate the expression and prognostic value of spindle and kinetochore-associated complex subunit 2(SKA2)in cervical cancer tissues,as well as its impact on the proliferation,migration and invasion of cervical cancer cells.Methods The expression of SKA2 in cervical cancer tissues was analyzed by bioinformatics database and immunohistochemical SP method,and the relationship between SKA2 expression level and clinicopathological features of cervical cancer patients and its prognostic value was analyzed.The mRNA expression of SKA2 in human normal cervical cells(HcerEpic)and cervical cancer cells(HeLa,SiHa,CaSki,C-33A)was detected by RT-qPCR.Cervical cancer cells SiHa with higher SKA2 expression level was selected for further study.SiHa cell model with down-regulated SKA2 expression was constructed,and its knockdown effect was verified.Cell proliferation capacity was detected by CCK-8 method,cell migration capacity was detected by cell scratch wound healing assay,and cell migration and invasion capacity was detected by Transwell assay.Results Compared with normal cervical tissues and cells,the expression levels of SKA2 mRNA and protein were higher in cervical cancer tissues and cells,and the differences were statistically significant(P<0.05).High SKA2 expression was associated with FIGO staging in patients with cervical cancer.Furthermore,SKA2 knockdown could inhibit the proliferation,migration and invasion of SiHa cells in cervical cancer(P<0.05).Conclusion SKA2 is up-regulated in cervical cancer tissues and cells,and can promote the proliferation,migration and invasion of cervical cancer cells.The expression level of SKA2 is associated with the progression of cervical cancer,and the prognosis of cervical cancer patients with high SKA2 expression is worse.

Objective:To explore the genotypes and frequency distribution of thalassemia in Lingui District,Guilin City,and provide reference for the prevention and control of thalassemia in this area. Methods:The results of genetic testing for thalassemia in 1501 suspected cases at the Second Affiliated Hospital of Guilin Medical University were analyzed retrospectively. The deletional mutations of α-thalassemia were detected by gap-PCR,the non-deletional mutations of α-thalassemia and β-thalassemia mutations were detected by PCR-reverse dot blot (PCR-RDB). Results:In 1501 samples,a total of 678 cases of thalassemia carriers were detected,with a detection rate of 45.17％. Among them,379 cases were α-thalassemia (including deletional α-thalassemia and non-deletional α-thalassemia),with a detection rate of 25.25％,the most common genotype was--SEA/αα (227 cases,15.12％),followed by-α3.7/αα (53 cases,3.53％). 270 cases of β-thalassemia were detected,with a detction rate of 17.99％,and βCD41-42/βN (144 cases,9.59％) was the main genotypes,followed by βCD17/βN (66 cases,4.40％) . In addition,there were 29 cases of αβ compound thalassemia,accounting for 1.93％,and the most common genotype was--SEA/αα complex βCD41-42/βN (5 cases,0.33％). Conclusion:Lingui District in Guilin City is a high-incidence area of thalassemia,and the genotypes of carriers are complex and diverse,with genetic heterogeneity. The results of this study provide a scientific basis for genetic counseling and prenatal diagnosis in this area.