Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

In recent years, China’s capacity for new drug research and development has been significantly strengthened, with major breakthroughs across multiple therapeutic areas, including cancer, autoimmune diseases, and metabolic disorders. An increasing number of domestically developed innovative drugs have been approved for marketing, gradually establishing a competitive position against imported drugs and expanding into global markets. This article systematically reviews the latest research progress of Class 1 innovative drugs in China from 2023 to 2024, categorizes representative approved drugs by therapeutic area, summarizes the clinical advantages and characteristics of representative drugs approved, analyzes in depth the current development trends of and challenges for China’s innovative pharmaceutical industry, and explores future directions, aiming to provide some reference for innovative drug research, industrial development, and policy-making in China.

Purpose To identify the distinct MRI findings of gastric-type endocervical adenocarcinoma(GEA)that can help differentiate it from usual-type endocervical adenocarcinoma(UEA)and reveal the radiologic-pathologic correlation.Materials and Methods All consecutive patients with cervical GEA(27 cases)and UEA(45 cases)treated at Shanghai First Maternity and Infant Hospital from January 2015 to August 2023 were included retrospectively.All patients underwent enhanced pelvic MRI examination.The clinical characteristics,tumor location,tumor shape,presence and size of cysts,and presence of hydrometra were evaluated between the two groups.Results The clinical characteristics included vaginal discharge in 12 cases of GEA and one case of UEA,vaginal bleeding in seven cases of GEA and 28 cases of UEA(P=0.048).Additionally,there were two cases of Peutz-Jeghers syndrome in GEA.Among the 27 GEA cases,the lesion was in the upper cervix in nine cases and involved the entire cervix in 16 cases;among the 45 UEA cases,the lesions were in the upper,lower and entire cervix in 12,29 and four cases,respectively(P=0.023).Regarding the tumor growth pattern,in the GEA group,there were nine cases of mass-forming growth pattern and 18 cases of diffuse infiltrative pattern;in the UEA group,there were 35 cases of mass-forming growth pattern and ten cases of diffuse infiltrative pattern,with a statistically significant difference(χ2=10.718,P=0.014).In 27 GEA cases,14 cases had observed intrauterine fluid,while in 45 UEA cases,eight cases had observed intrauterine fluid(χ2=12.657,P=0.002).Among the GEA cases,five had no cysts,12 had microcysts and ten had macrocysts;among the UEA cases,14 had no cysts,31 had microcysts and macrocysts were not observed(P=0.001).The maximum diameter of the GEA masses was(4.030±0.375)cm,and that of UEA masses was(2.315±0.769)cm,with a statistically significant difference(t=7.134,P<0.001).Conclusion By integrating multiple MRI features of the diffuse infiltrative growth pattern(such as the predominant location in the upper or entire cervix,frequent association with uterine cavity effusion or larger cysts,and a maximum mass diameter≥4 cm),it aids in distinguishing GEA from UEA.

Objective To investigate the clinical value of baseline 18F-fluorodeoxyglucose(18F-FDG)PET/CT metabolic parame-ters and certain clinical indicators in predicting the prognosis of patients with diffuse large B-cell lymphoma(DLBCL).Methods A retrospec-tive analysis was conducted on the baseline 18 F-FDG PET/CT data of 73 DLBCL patients who received R-CHOP treatment.Patients were divided into progression group(24 cases)and non-progression group(49 cases)based on disease progression within 2 years post-treatment.The lesion maximum standardized uptake value(SUVmax),tumour-to-liver blood pool SUVmax ratio(LLR)and tumour-to-mediastinal blood pool SUVmax ratio(L-BPR)were analyzed using receiver operating characteristic(ROC)curves.Kaplan-Meier(K-M)survival curves analysis were performed based on the optimal thresholds of SUVmax,LLR and L-BPR.x2 tests were used to analyze and compare the relationship between each parameter and disease progression.Indicators that were significant in the x2 tests were included in the multivariate Cox regression analysis.Results The area under the curve(AUC)for LLR,L-BPR,and SUVmax were 0.920,0.914,and 0.848,respectively,with optimal thresholds of 7.41,10.67,and 14.70.Based on these thresholds,K-M survival curves analysis showed that the 2-year progression-free survival(PFS)rates for DLBCL patients were 79.2％vs 30.8％(P＜0.001),74.3％vs 22.0％(P=0.009),and 79.5％vs 51.6％(P=0.002),respectively.Significant differences were observed between the progression and non-progression groups in terms of LLR,L-BPR,SUVmax,extranodal involvement,international prognostic index(IPI)score,lactate dehydrogenase(LDH)level,Eastern Cooperative Oncology Group(ECOG)score,and β2-microglobulin(β2-MG)levels(P＜0.05).Multivariate Cox regression analysis revealed that the IPI score and LLR were independent predictors affecting the 2-year PFS of DLBCL patients(P＜0.05).Conclusion Baseline 18F-FDG PET/CT metabolic parameter LLR and IPI score are inde-pendent factors for predicting the prognosis of DLBCL patients.

Demethyleneberberine(DMB),one of the active me-tabolite of berberine,displays versatile pharmacological proper-ties.Numerous studies indicate diverse biological activities,such as actions against infection,inflammation,fibrosis,cancer cells,blood lipids,etc.It presents considerable potential in treating neurodegenerative diseases.This article provides a con-cise review of the pharmacological actions and mechanisms made in demethyleneberberine research to facilitate a deeper under-standing of its pharmacology and provide a scientific foundation for its prudent development.

This study was aimed at preliminarily investigating the genetic and antimicrobial resistance characteristics of Salmonella Alachua isolates through whole-genome analyses.Five Salmonella Alachua isolates from various sources(both hu-man and non-human)were collected and identified.Phenotype and serotype verification,antimicrobial susceptibility testing,and whole-genome sequencing were performed.Virulence genes,antimicrobial resistance genes,and plasmid replicons were predicted according to globally available Salmonella Alachua genomic data.A phylogenetic tree was constructed to explore the genetic background.The first report of Salmonella Alachua in China emerged in Shanghai in 2015,and patients presented pri-marily with diarrhea.The isolates have been found predominantly in the eastern and southern coastal regions.Among the five i-solates analyzed,four belonged to sequence type(ST)2061,and one belonged to ST1298.All isolates were susceptible to most commonly used clinical antibiotics.Whole-genome analyses revealed that two ST2061 strains carried the blaKPC-2 gene,and one ST1298 strain carried the fosA7 gene.Phylogenetic analysis of global Salmonella Alachua populations indicated that the ST2061 clone belonged to the C1 clade,which was closely related to strains from the UK,whereas the ST1298 clone was found in the C4 clade,a globally disseminated fosA 7-positive lineage.This study provides initial insights into the genetic and antimi-crobial resistance characteristics of Salmonella Alachua in China,highlighting the presence of strains carrying blaKPC-2 and fo-sA7 genes.These findings may provide a reference for future large-scale molecular epidemiological surveillance and source-trac-ing efforts,and they underscore the importance of enhanced resistance monitoring for Salmonella Alachua.

Objective To observe the effects of LINC01915 on the proliferation,migration and invasion of human colorectal cancer cells,and to explore its possible regulatory mechanism.Methods The colorectal cancer cell lines of SW620,SW480,LOVO,HCT116 and the normal colorectal cell line of NCM460 were selected,and the expression of LINC01915 was detected by RT-qPCR.HCT116 cell line with the highest expression of LINC01915 was taken and divided into the upregulation group,the downregulation group,the upregulation control group,the downregulation control group and the blank group.The transfection efficiency of each group was detected by fluorescence microscope;RT-qPCR was used to detect the expression of LINC01915 in each group;methyl thiazolyl tetrazolium(MTT)assay was used to detect the proliferative activity in each group;scratch wound healing assay and Transwell assay were used to detect the migration and invasion activities in each group;RT-qPCR was used to detect the expression of miR-92a-3p and mRNA expression of large tumor suppressor homolog 2(LATS2),transcription factor 21(TCF21)and Kruppel like factor 4(KLF4);and Western blot was used to detect the expression of LATS2,TCF21,and KLF4 proteins.Dual-fluorescein reporter assay was used to verify the targeting relationship between LINC01915 and miR-92a-3p.Results The expression of LINC01915 in various human colorectal cancer cell lines were lower than that in the NCM460 cell(P<0.05),and the highest LINC01915 expression in human colorectal cancer cell lines was observed in HCT116(P<0.05).The transfection efficiency of cells in each transfection group was high.Compared with the blank group and the upregulation control group,the expression of LINC01915,and mRNA and protein expression of LATS2,TCF21,and KLF4 in the upregulation group increased(P<0.05),and the A value,scratch healing rate,number of invasive cells and miR-92a-3p expression decreased(P<0.05).Compared with the blank group and the downregulation control group,the expression of LINC01915,and mRNA and protein expression of LATS2,TCF21,and KLF4 in the downregulation group decreased(P<0.05),and the A value,scratch healing rate,number of invasive cells and miR-92a-3p expression increased(P<0.05).LINC01915 had binding sites with miR-92a-3p,and compared with the miR-NC group,the miR-92a-3p mimics group showed a decrease in the luciferase activity of WT-LINC01915(P<0.05).Conclusion The expression of LINC01915 in the human colorectal cancer cell lines decreases,and upregulation of LINC01915 expression can inhibit cell proliferation,migration,and invasion,which may be related to the up-regulation of the expression of LATS2,TCF21 and KLF4 by inhibiting miR-92a-3p.

Objective To explore the clinical efficacy and medical costs of high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,and high ligation of the great saphenous vein combined with foam sclerotherapy for treating varicose of great saphenous vein.Methods The clinical data of patients with varicose of great saphenous vein undergoing high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,or high ligation of the great saphenous vein combined with foam sclerotherapy were analyzed retrospectively.The evaluation included efficacy assessment,quality of life evaluation,hospitalization days and costs,postoperative complications,and recurrence after surgery.Results There were no statistical differences in gender,age,disease course and clinical etiology anatomy pathophysiology(CEAP)grading system among the three groups(P＞0.05).The clinical efficacy assessments in all patients among the three groups showed significant effects at 3 and 6 months postoperatively.One patient in the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy suffered deep vein thrombosis of lower extremity after operation.In terms of quality of life,there was no statistically significant difference in venous clinical severity score(VCSS)among the three groups at 3 months postoperatively(P＞0.05).The group treated with simple foam sclerotherapy showed significantly shorter hospitalization days compared with the other two groups.Additionally,the group treated with simple foam sclerotherapy showed lower hospitalization expenses,which was not statistically significant when compared to the group treated with high ligation and stripping of the great saphenous vein group(P＞0.05),but there was a statistical difference compared to the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy(P＜0.05).Conclusion There are no significant differences in clinical efficacy,postoperative pain,and quality of life evaluation among the three methods.However,simple foam scle-rotherapy may reduce the length of hospitalization stay and direct medical costs.

Objective To explore the clinical efficacy and medical costs of high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,and high ligation of the great saphenous vein combined with foam sclerotherapy for treating varicose of great saphenous vein.Methods The clinical data of patients with varicose of great saphenous vein undergoing high ligation and stripping of the great saphenous vein,simple foam sclerotherapy,or high ligation of the great saphenous vein combined with foam sclerotherapy were analyzed retrospectively.The evaluation included efficacy assessment,quality of life evaluation,hospitalization days and costs,postoperative complications,and recurrence after surgery.Results There were no statistical differences in gender,age,disease course and clinical etiology anatomy pathophysiology(CEAP)grading system among the three groups(P＞0.05).The clinical efficacy assessments in all patients among the three groups showed significant effects at 3 and 6 months postoperatively.One patient in the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy suffered deep vein thrombosis of lower extremity after operation.In terms of quality of life,there was no statistically significant difference in venous clinical severity score(VCSS)among the three groups at 3 months postoperatively(P＞0.05).The group treated with simple foam sclerotherapy showed significantly shorter hospitalization days compared with the other two groups.Additionally,the group treated with simple foam sclerotherapy showed lower hospitalization expenses,which was not statistically significant when compared to the group treated with high ligation and stripping of the great saphenous vein group(P＞0.05),but there was a statistical difference compared to the group treated with high ligation of the great saphenous vein combined with foam sclerotherapy(P＜0.05).Conclusion There are no significant differences in clinical efficacy,postoperative pain,and quality of life evaluation among the three methods.However,simple foam scle-rotherapy may reduce the length of hospitalization stay and direct medical costs.

Barrett's esophagus(BE),a precancerous state of esophageal adenocarcinoma,poses a major challenge for prevention and treatment owing to its complex mechanism of inflammation-cancer transformation and the lack of effective clinical treatment and torsion strategies.Building upon the"preventing disease progression"theory,this study aimed to address the critical clinical challenge of intercepting the pathological progression during the inflammation-cancer transformation of BE by proposing an innovative"two critical nodes-three stages"pathomechanism framework.The pathogenesis of BE originates from liver depression and qi stagnation.The pathological progression evolves through two critical nodes:liver depression transforming into heat and heat transforming into blood stasis,representing a three-stage evolutionary pattern of qi stagnation,heat transformation,and blood stasis formation.Acidic bile salts,acting as a pathogenic toxin,permeate the entire process and catalyze carcinogenesis.Based on this understanding,the therapeutic principles of"treatment from the liver"and"truncation and torsion"were established,emphasizing stage-specific interventions.For the qi stagnation stage,treatment focuses on soothing the liver and regulating qi,as well as moistening,harmonizing,and descending the qi.This is achieved by combining modified Chaihu Shugan Powder with Xuanfu Daizhe Decoction,while using pungent and drying herbs cautiously and supplementing them with light and floral herbs.In the heat transformation stage,the strategy aims to clear the liver and drain heat while protecting yin and harmonizing the stomach,employing modified Huaganjian combined with Yiguanjian and supplemented with Jinlingzi Powder to clear depressed fire.For the blood stasis formation stage,treatment involves activating blood and resolving stasis,combined with supporting healthy qi and removing toxins.This is achieved using a modified Gexia Zhuyu Decoction,supplemented with Liujunzi Decoction,and additions such as Radix Salviae Miltiorrhizae and turtle carapace to disperse nodules and reduce masses.This theoretical framework establishes a diagnostic and therapeutic model characterized by the integration of disease mechanisms with pathology and the mutual reference of macro-level signs with micro-level indicators.It provides a comprehensive clinical practice pathway,complete with principles,methods,formulas,and herbs,for the stage-specific interception of inflammation-cancer transformation in BE using traditional Chinese medicine.