Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

Melicope pteleifolia is a plant belonging to the Melicope genus of the Rutaceae family. Known for a bitter taste and cold nature, its stems and tender branches with leaves possess properties of clearing heat, detoxifying, dispelling wind, and removing dampness and can be used to treat sore throat, malaria, jaundice hepatitis, rheumatic bone pain, eczema, dermatitis, and sores and ulcers. In this study, 19 compounds were isolated from the chloroform and n-butanol extracts of M. pteleifolia leaves by using liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR)-guided separation techniques. The compounds were identified as isoleptonol(1), leptaones B-E(2-5), friedelin(6), evodionol(7), ethyl p-hydroxybenzoate(8), litseachromolaevane A(9), quercetin-7,3',4'-trimethyl ether(10), kokusaginin(11), 8-(1-hydroxyethyl)-5,6,7-trimethoxy-2,2-dimethyl-2H-1-benzopyran(12), ethyl p-hydroxycinnamate(13), 3-hydroxy-9-methyl-6H-benzo\[c\]chromen-6-one(14), agrimonolide(15), 7-hydroxycoumarin(16), scopoletin(17), isoscutellarein(18), and agrimonolide 6-O-glucoside(19). Among these, the new compounds included one chromene and four meroterpenoid(1-5). The anti-inflammatory activities of the newly identified compounds 1-5 were screened in vitro, showing that the five compounds(1-5) exhibited inhibitory effects on nitric oxide(NO) production in BV2 cells induced by lipopolysaccharide(LPS)/interferon(IFN)-γ, with IC_(50) values ranging from 12.25 to 36.48 μmol·L~(-1).
Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Rutaceae/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; Nitric Oxide/immunology*

OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

OBJECTIVE: The aim of this study is to re-evaluate the systematic reviews and meta-analyses on statins for the treatment of erectile dysfunction (ED) and construct an umbrella review, thereby providing robust evidence-based for the clinical application of statins in ED treatment. METHODS: A comprehensive computerized search was conducted across CNKI, Wanfang Database, VIP, WOS, Embase, PubMed, and Cochrane Library databases from their inception to September 12, 2024, for all systematic reviews and meta-analyses addressing statin interventions in ED. The methodological quality, reporting quality, and evidence quality of the included studies were assessed and summarized using PRISMA 2020, AMSTAR 2, and GRADE systems. RESULTS: Four systematic reviews and meta-analyses were included. According to the AMSTAR 2 evaluation, one paper was rated as low quality, while the remaining three were classified as very low quality. PRISMA 2020 evaluation results indicated that the average score of the four included studies was 29, with all being of medium quality but exhibiting partial deficiencies. The proportion of fully consistent items across the four studies ranged from 52.38% to 80.95%. GRADE system tool evaluation revealed 11 outcome indicators, of which only one was rated as intermediate evidence. The remainders were categorized as low or very low evidence, with no high-quality evidence identified. CONCLUSION Statins demonstrate efficacy in treating ED. However, the current quality of relevant systematic reviews is suboptimal, with notable deficiencies in methodological, reporting, and evidential quality. Further high-quality studies are warranted to provide more reliable evidence-based medical guidance for clinical practice.
Humans ; Erectile Dysfunction/drug therapy* ; Male ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Meta-Analysis as Topic ; Systematic Reviews as Topic

The objective assessment of hearing loss is one of the critical components in forensic clini-cal research.Auditory brainstem response(ABR)is an important method for objectively assessing hearing levels.It is divided into various types based on different stimulus signals,each with its own characteris-tics and applications.Among them,narrow-band Chirp ABR,due to its frequency specificity,fulfills the basic requirements for objective assessment of forensic audiology,promising to be an important method of objective hearing assessment in forensic medicine.This article reviews the development history,charac-teristics and clinical applications of Chirp ABR,and envisions its application prospects in forensic audi-tory identification.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

Objective To explore the effect of shikonin on the recovery of nerve function after acute spinal cord injury(SCI)in rats.Methods 96 male Sprague-Dawley(SD)rats were divided into 4 groups randomly:sham operation group(Group A),sham operation+shikonin group(Group B),SCI+DMSO(Group C),SCI+shikonin group(Group D).The acute SCI model of rats was made by clamp method in groups C and D.After subdural catheterization,no drug was given in group A.rats in groups B and D were injected with 100 mg·kg-1 of shikonin through catheter 30 min after modeling,and rats in group C were given with the same amount of DMSO,once a day until the time point of collection tissue.Basso-Beattie-Bresnahan(BBB)scores were performed on 8 rats in each group at 6,12,and 3 d after moneling,and oblique plate tests were performed on 1,3,7 and 14 d after modeling,and then spinal cord tissues were collected.Eight rats were intraperitoneally injected with propidine iodide(PI)1 h before sacrificed to detection PI positive cells at 24 h in each group.Eight rats were sacrificed in each group at 24 h after modeling,the spinal cord injury was observed by HE staining.The Nissl staining was used to observe survivor number of nerve cells.Western-blot technique was used to detect the expression levels of Bcl-2 protein and apoptosis related protein RIPK1.Results After modeling,BBB scores were normal in group A and B,but in group C and D were significantly higher than those in group A and B.And the scores in group D were higher than those in group C in each time point(P＜0.05).At 12 h after modeling,the PI red stained cells in group D were significantly reduced compared with that in group C,and the disintegration of neurons was alleviated(P＜0.05).HE and Nissl staining showed nerve cells with normal morphology in group A and B at 24h after operation.The degree of SCI and the number of neuronal survival in group D were better than those in group C,the differ-ence was statistically significant at 24h(P＜0.05).The expression of Bcl-2 and RIPK1 proteins was very low in group A and B;The expression of RIPK1 was significantly increased in Group C and decreased in Group D,with a statistically significant dif-ference(P＜0.05);The expression of Bcl-2 protein in group D was significantly higher than that in group C(P＜0.05).Conclu-sion Shikonin can alleviate the pathological changes after acute SCI in rats,improve the behavioral score,and promote the re-covery of spinal nerve function.The specific mechanism may be related to the inhibition of TNFR/RIPK1 signaling pathway mediated necrotic apoptosis.

Objective To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group.Methods Forty healthy subjects (12 males and 28 females) were recruited.A portable digital quantitative muscle strength tester,Micro FET2TM,was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension,0° neutral,and 30° flexion,respectively.Palmar abduction strength of the thumb was measured at 30° and 60°,respectively.Ten subjects were randomly selected from the 40 subjects,and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days.Results Except for the fact that in males,there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position,the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics:30° of wrist extension>neutral 0° posi-tion>30° of flexion,and the PAST was 30°>60°;The flexor muscle strength of all the subjects was thumb>index finger>middle finger>ring finger>little finger;All muscle strength values of male were greater than those of female,and the difference was statistically significant (P<0.05);There was no significant difference between the left and right side muscle strength values of all subjects (P>0.05).The reliability of muscle strength values measured at different times in 10 subjects was good.Conclu-sion The quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position,and a standardized and uniformed test position should be adopted in the actual identification.Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing.The 30° ex-tension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint.The 30° position can be used as the best standardized test position for PAST.

Chronic atrophic gastritis(CAG)is a common intractable gastric disease in clinic,which belongs to the gastric precancerous lesions.Professor LIU Feng-Bin and his team have performed the exploration and practice in the field of CAG for more than 30 years,and they proposed that the evolution of the traditional Chinse medicine(TCM)pathogenesis of inflammation-to-tumor transition(ITT)in CAG was characterized by spleen deficiency being the root cause,qi stagnation,blood stasis and dampness retention being the branch cause,and stasis and toxin being the aggravating factors.Deificiency of the spleen and stomach is the initial factor of CAG,which influences the whole process of the disease.Qi stagnation,blood stasis and dampness retention are the triggering and aggravating factors for the ITT in CAG.The formation of blood stasis and toxin is the key to the progression and transition of CAG.Treatment of ITT in CAG should be based on the results of syndrome differentiation and gastroscopic findings by staging therapy.Before treatment,disease dianosis and syndrome differentiation should be made,and macro and micro syndrome differentiation should be carried out for assistance.Therapy of strengthening the spleen and supporting healthy qi should be implemented throughout the whole process of the disease.The early stage of CAG has the features of gastric mucosa with mild to moderate atrophy and with or without mild intestinal epithelial hyperplasia,the pathogenesis of early CAG is characterized by weakness of the spleen and stomach and is accompanied with the pathological factors of qi stagnation,damp-retention and blood stasis,and the basic treatment should adopt the therapies of strengthening the spleen and clearing heat,regulating qi and activating blood stasis.The advanced stage of CAG has the features of severe atrophic gastric mucosa with or without moderate to severe intestinal epithelial and/or mild to moderate intraepithelial neoplasia,the pathogenesis is characterized by weakness of the spleen and stomach,phlegm blended with blood stasis,and stasis-toxin in the gastric collaterals,and the basic treatment should adopt the therapies of supporting healthy qi and dissipating masses,and unblocking the collaterals and removing toxin,so as to construct an intact line to blocking the ITT in CAG with traditional Chinese medicine.