The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Vacuum compression molding (VCM) is a novel technology supporting the research and development of pharmaceutical solid dispersions. It is widely applied due to its precision and convenience in sample preparation. This technology integrates the principles of heating, melting, cooling, and vacuum compression to transform solid powders into shaped solids directly. By selecting different molds, temperatures, and pressures, researchers can prepare samples with diverse characteristics. This paper presents an overview of the equipment composition and working principles of VCM technology, demonstrating its distinct advantages in the formulation screening process of amorphous solid dispersions through comparative analysis with hot melt extrusion using case studies, and introduces its applications in the development of drug delivery systems and rheological characterization analysis, with a perspective on the future development of its functions.

Objective To investigate the clinical effect of ultrasound induction combined with acupunc-ture points and polyethylene glycol 4000 powder for treating constipation in elderly patients with hip fracture. Methods A randomized parallel controlled method was adopted.A total of 100 inpatients meeting the inclu-sion criteria were divided into the control group and treatment group.Fifty cases in the control group were given polyethylene glycol 4000 powder,10 g/d,taking at a draught in 1 h after lunch.Fifty cases in the treat-ment group adopted the ultrasound induction combined with Shenque acupoint and Guanyuan acupoint,which was implemented at 1 h after lunch every day,once a day,30 min each time,and the intensity was appropriate for the patients to tolerate.The two groups were continuously treated for 1 week.The clinical symptoms be-fore and after treatment in the two groups were observed.The constipation score,quality of life score,treat-ment efficacy and safety were compared between before and after treatment.Results There were 3 dropout cases in the control group and 47 cases were finally included.Among them,14 cases were excellently effective,20 cases were effective,13 cases were ineffective,and the total effective rate was 72.34％;there were 2 dropout cases in the treatment group and 48 cases were finally included.Among them,15 cases were excellently effec-tive,18 cases were effective,15 cases were ineffective,and the total effective rate was 68.75％;the total effec-tive rate had no statistical difference between the two groups (P>0.05).The effect onset time of the treat-ment group was earlier than that of the control group with statistical difference (P<0.05).The abdominal symptom dimension and total score in the constipation scores after treatment in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05).After treat-ment,the physiological,satisfaction dimension scores and total score in life quality score in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05). During the test process,2 cases in the control group had adverse drug reactions,which manifested by mild di-arrhea at the end of the treatment course,and no adverse reactions were found in the treatment group.Conclu-sion The ultrasound induction combined with acupuncture points for treating constipation in elderly patients with hip fracture has equivalence with polyethylene glycol 4000 powder,moreover which has the advantages in the aspects of effect onset time and improvement of abdominal symptoms.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective:To investigate the clinical efficacy of arthroscopic modified anatomic glenoid reconstruction with Enden-Hybinette procedure combined with loop plate fixation in the treatment of recurrent anterior dislocation of shoulder combined with severe glenoid bone loss.Methods:A retrospective case series study was conducted to analyze 36 patients with recurrent anterior dislocation of the shoulder combined with severe glenoid bone loss who were admitted to 901st Hospital of the Joint Logistics Support Force of PLA from January 2019 to January 2021, including 28 males and 8 females, aged 18-33 years [(29.5±3.0)years]. All the patients had injury history. The dislocation frequency range was 2-40 times [(20.5±6.5)times]. Beighton scale scores were 3-9 points [(4.0±0.8)points]. All the patients underwent anatomic reconstruction of the glenoid bone with arthroscopic modified Enden-Hybinette procedure using iliac autograft and loop plate elastic fixation. Posterior glenoid version angle, the breadth of the glenoid cavity and the A-P glenoid cavity depth were measured and osseous anatomy of the reconstructed glenoid bone was evaluated. Union of the Iliac bone block and glenoid bone loss was observed and the absorption rate of the bone block was evaluated at 6 months after surgery. The shoulder stability score, functional activity score, joint range of motion score and total Rowe score of shoulder function were used to evaluate the shoulder stability, functional activity and movement before surgery, at 3, 6 months after surgery and at the last follow-up. The incidence of complications was observed.Results:All the patients were followed up for 12-24 months [(18.8±3.5)months]. At 1, 3, 6 months after surgery and at the last follow-up, posterior glenoid version angle was (11.3±1.7)°, (10.6±1.2)°, (9.1±2.0)° and (9.2±1.9)° respectively; the breadth of the glenoid cavity was (34.2±1.3)mm, (33.2±1.0)mm, (32.2±1.0)mm and (31.3±1.1)mm respectively; the A-P glenoid cavity depth was (2.6±0.1)mm, (2.4±0.1)mm, (2.3±0.2)mm and (2.2±0.2)mm respectively, which were all significantly improved compared with those before surgery [(-5.9±1.0)°, (24.3±1.2)mm and (0.6±0.1)mm respectively] ( P<0.01), with no significant differences among those at different postoperative time points ( P>0.05). Bony union was observed in the iliac bone block and glenoid bone loss after bone grafting in all the patients at 6 months after surgery and the iliac bone block resorption rate was (20.5±4.1)%. At 3, 6 months after surgery and at the last follow-up, the shoulder stability score was (41.5±6.1)points, (43.9±6.3)points and (44.7±5.0)points respectively; the functional activity score was (26.9±2.5)points, (27.1±2.5)points and (28.6±2.3)points respectively; the joint range of motion score was (13.9±1.0)points, (14.9±1.2)points and (15.8±1.5)points respectively; the total Rowe score of shoulder function was (81.4±11.5)points, (85.8±12.3)points and (86.4±9.8)points respectively, which were significantly improved compared with those before surgery [(6.1±1.5)points, (11.9±1.5)points, (8.5±1.4)points and (27.4±7.5)points respectively] ( P<0.01), with no significant differences among those at different postoperative time points ( P>0.05). At the follow-up, no complications such as incision infection, neurological injuries, implant failure of displacement, recurrent re-dislocation of the shoulder or osteoarthritis were observed. Conclusion:Arthroscopic modified anatomic glenoid reconstruction with Enden-Hybinette procedure combined with loop plate fixation in the treatment of recurrent anterior dislocation of shoulder combined with severe glenoid bone loss has the advantages of better osseous anatomy of the reconstructed glenoid bone, better bony union, satisfactory shoulder stability, functional restoration, etc.

The nasal swab samples of swine influenza(SI)suspected pigs were collected and tested for H3 subtype swine influenza virus(SIV)positive by RT-qPCR.The positive samples were inoc-ulated into SPF chicken embryos for virus isolation.The full genome sequencing and sequence anal-ysis of the isolated H3N2 subtype SIV were conducted,and its pathogenicity was studied.The re-sults showed that a strain of SIV was successfully isolated and identified as H3N2 subtype by RT-PCR,named A/Swine/Yunnan/KM/06/2023(H3N2).The BLSAT results showed that the eight segments of SIV H3N2 KM had the highest homology with eight different strains of swine influ-enza or human influenza viruses,reaching 95.41％-97.49％.The HA and NA segments were de-rived from H3N2 subtype SIV,the NP segment was derived from H1N1 subtype human influenza virus,the M segment was derived from H1N2 subtype SIV,and all other segments were derived from H1N1 subtype SIV.The key receptor sites(190D,223V,226I,228S)of HA protein remained unchanged.The pathogenicity experiment results showed that infected piglets exhibited symptoms such as fever,sneezing,runny nose,the virus could be detoxified to the outside through the nasal cavity,and the lungs had different degrees of lesion.Immunohistochemistry(IHC)showed that the virus could replicate in the lungs.In conclusion,a strain of H3N2 subtype SIV was successfully iso-lated,and the genetic evolution,molecular characteristics and pathogenicity of the virus were stud-ied.It revealed that H3N2 subtype SIV is constantly evolving and had pathogenicity to piglets,pro-viding a reference for monitoring and preventing SIV epidemics in China,and provided a candidate strain for SI vaccine development.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

AIM:To assess the evolving burden of cataracts in China from 1990 to 2019.METHODS: Data on disease burden related to cataracts in China were retrieved from the Global Burden of Disease(GBD)2019 study based on large public databases. Utilizing data from the GBD 2019 study, we extracted information on cataract-related disease burden in China from extensive public databases. Analysis of prevalence and disability-adjusted life years(DALYs)associated with cataracts in China was conducted based on GBD 2019 findings. The variable characteristics of age-standardized prevalence rates(ASPR)and age-standardized DALYs rates(ASDR)in China and its neighboring countries were also explored.RESULTS: Between 1990 and 2019, the number of prevalent cases of blindness and vision loss caused by cataracts in China increased by 223.54%, and the corresponding DALYs raised by 142.14%. Over the past 30 years, females exhibited higher age-standardized prevalence and DALYs rates compared to males. Meanwhile, individuals aged 65 to 84 years were found to be more susceptible to cataracts than other age groups. Compared with neighboring countries, China ranked from the 9th position in 1990(867.09, 95%UI: 761.36 to 975.42, per 100 000 population)to the 11th in 2019(991.56, 95%UI: 861.52 to 1131.04, per 100 000 population)in ASPR, while from the 9th in 1990(65.85, 95%UI: 46.39 to 89.41, per 100 000 population)to the 10th position in 2019(59.16, 95%UI: 41.70 to 80.15, per 100 000 population)in ASDR. However, on a global scale, China maintained relatively low ASDR and ASPR for cataracts in 2019.CONCLUSION: The study highlights a substantial rise in the prevalence and DALYs associated with blindness and vision loss due to cataracts from 1990 to 2019 in China, and underscores the urgent need for increased early screening of cataracts, particularly among the elderly and females.

Objective To explore the clinical significance of nucleolar antinuclear antibodies(ANA)in re-lated diseases.Methods This study was a retrospective study.Clinical samples of 71780 patients who visited the hospital from January 2017 to May 2022 were collected.Indirect immunofluorescence was used to detect ANA in clinical samples.Statistical analysis was conducted on the positivity rate of nucleolar ANA in clinical patients,as well as the relevant clinical information and laboratory characteristics of patients with autoimmune diseases(AID)with nucleolar ANA positivity.Results Among 71780 patients who underwent routine ANA testing,16778 were positive for ANA,with a positive rate of 23.37％.Among them,there were 1 708 cases of nucleolar type,accounting for 2.38％of all routine ANA tests,and the proportion of ANA positive cases was 10.18％.There was a statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the＞20-＜50 year old group and the ≥ 50 year old group(P＜0.05),while there was no statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the ≤ 20 year old group(P＞0.05).There was a statistically significant difference in the positivity rate of nucleolar ANA among women of different age groups(P＜0.05),among them,the highest positive rate of nucleolar ANA was found in women aged between 20 and 50 years old.There was no statistically significant difference in the positive rate of nucleolar ANA among males of different age groups(P＞0.05).The positivi-ty rate of ANA was the highest among patients in the Department of Rheumatology and Immunology(70.35％),but nucleolar ANA positivity was mainly seen in departments such as Reproductive Medicine Cen-ter(12.90％),Respiratory Medicine(12.40％),and Neurology(11.29％),and the difference in positivity rates between departments was statistically significant(P＜0.05).Out of 1 708 nucleolar ANA positive indi-viduals,420 underwent ANA titers,including 34 AID patients and 386 non AID patients.There was no statis-tically significant difference in nucleolus positive titers between non AID patients and AID patients(P＞0.05).Conclusion The nucleolus type is a common fluorescence pattern in ANA positive individuals,and there are gender and age differences in ANA positive individuals.The positive rate and titer of nucleolar ANA vary among different AID diseases.Combined with other immune function indicators,and it is helpful for early differential diagnosis of AID.