OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Neuropathic pain(NPP)is a recurrent and intractable pain syndrome,and microglial polarization is closely related to it.Recent studies have shown that after cell polarization,M1 pro-inflammatory and M2 anti-inflammatory types could be formed,and M1 and M2 microglial cells are involved in NPP through the modulation of inflammatory responses.The two types of microglial cells have different roles in NPP,just like a double-edged sword.M1 pro-inflammatory type plays an injurious role in NPP through the release of pro-inflammatory factors and noxious substances,whereas M2 anti-inflammatory type plays a protective role by secreting anti-inflammatory factors.In this article,the role of microglia polarization on NPP are reviewed.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

ObjectiveTo explore the clinical efficacy of Dingkundan in the treatment of ovulation disorder infertility based on the real world and provide reliable evidence-based medical support for clinical practice. MethodClinical diagnosis and treatment data of patients with ovulation disorder infertility in the real world were collected through the Medroad Cloud system. Patients were grouped according to their real-world treatments， and the total effective rate， ovulation rate per cycle， number of days of follicle development， gonadotropin （Gn） dosage， levels of mature follicle-related hormones， endometrial thickness and classification， pregnancy rate per cycle， clinical pregnancy rate， ectopic pregnancy rate， and early pregnancy loss rate were observed. ResultA total of 207 patients were included， and the most common traditional Chinese medicine （TCM） syndrome in the entire population was liver depression and kidney deficiency. The patients were divided into a Chinese medicine group （Dingkundan， 60 cases）， a western medicine group （ovulation induction， 51 cases）， and a combination group （Dingkundan + ovulation induction， 96 cases）. The combination group（98.96%，95/96） had the highest total effective rate， which was statistically significant when compared with the Chinese medicine group（88.33%，53/60） （χ²=8.328， P<0.05）. The mature follicle estradiol （E₂） and luteinizing hormone （LH） levels were the highest in the combination group， and there were statistically significant differences when compared with the western medicine group （P<0.01）. The endometrial thickness was higher in the Chinese medicine group and the combination group than in the western medicine group （P<0.01）. The proportion of type A endometrium was highest in the combination group（85.90%，201/234）， and there was a statistically significant difference when compared with the western medicine group（73.81%，93/126） （χ²=7.993， P<0.01）. The clinical pregnancy rate was 60.42%（58/96） in the combination group， which was higher than 36.67%（22/60） in the Chinese medicine group （χ²=8.336， P<0.01） and 39.22%（20/51） in the western medicine group （χ²=6.011， P<0.05）. Compared with the western medicine group， the combination group showed a favorable trend in total effective rate， ovulation rate per cycle， number of days of follicle development， Gn dosage， pregnancy rate per cycle， ectopic pregnancy rate， and early pregnancy loss rate， but the differences were not statistically significant. ConclusionIn real-world clinical practice， the combination of Dingkundan with ovulation induction can increase endometrial thickness， improve the proportion of type A endometrium， enhance egg quality， and increase the clinical pregnancy rate in patients with ovulation disorder infertility. This approach deserves further clinical research and application.

Objective:To explore the application value of guide tube fenestration and drainage technology in intracranial artery stenting surgery.Methods:A total of 120 patients with symptomatic intracranial atherosclerotic stenosis admitted to the Xingtai Third Hospital from January 2021 to December 2022 were selected and randomly divided into an observation group ( n=60) and a control group ( n=60). Both groups were treated with intracranial artery stenting, with the observation group receiving guidance catheterization and window opening technique during the surgery. Two groups of surgeries were observed and compared: the degree of vascular stenosis before and after surgery, the Montreal Cognitive Assessment Scale (MoCA) scores before and one month after surgery, intraoperative complications, and prognosis. Results:The surgical time and catheter placement time in the observation group were (110.20±23.32)minutes and (11.32±2.01)minutes, respectively, which were significantly shorter than those in the control group (all P<0.05). The stent placement rate and operation success rate in the observation group were 95.00% and 96.67%, respectively, significantly higher than those in the control group (all P<0.05). The degree of postoperative vascular stenosis in the observation group was (32.29±7.11)%, significantly milder than that in the control group [(44.43±8.15)%, P<0.05]. One month after surgery, the MoCA scores of both groups improved significantly compared to before surgery (all P<0.05), and there was no statistically significant difference between the groups ( P>0.05). There was no statistically significant difference in the incidence of collateral circulation occlusion and vascular rupture between the two groups (all P>0.05). During the follow-up period, there was no statistically significant difference in the incidence of restenosis, intracranial hemorrhage, and recurrent ischemic stroke between the observation group and the control group (all P>0.05); The good prognosis rate of the observation group was 73.33%, significantly higher than that of the control group (53.33%, P<0.05). Conclusions:The application of guided catheter fenestration technique in intracranial artery stenting has good value, which is beneficial for improving the stent placement rate and operation success rate, and improving the degree of vascular stenosis.

Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

Objective Based on the screening of respiratory viruses in children with respiratory tract infection in Maoming,the viral pathogens in children with respiratory tract infection were investigated,the epidemic trend of children with respiratory tract infection in the region was grasped,so as to provide the basis for the disease diagnosis of children with respiratory tract infection.Methods With direct immunofluorescence,7 common respiratory viruses in nasopharyngeal secretions were detected in 13 148 patients with respiratory infection in our hospital,including adenovirus (ADV),respiratory syncytial virus (RSV),influenza virus A (FLUA),influenza virus B FLUB) and parainfluenza (PIV).Results In 13 148 cases,the respiratory virus positive were found in 3 308 cases,the total positive rate was 25.16％,the positive detection rate of RSV was the highest (17.39 ％),and the detection rate of respiratory virus has obvious seasonal characteristics,with the highest detection rate in the first quarter,and mainly concentrated in the population under the age of three.Conclusion RSV was the first of the 7 common respiratory viruses detected,and the virus infection was associated with age and season.

Objective: To analyze the effect and adverse reactions of radiotherapy in patients with primary orbital lymphoma. Methods: A total of 28 patients with primary orbital lymphoma from Tianjin Union Medical Center, the First Central Hospital of Tianjin and Tianjin Dagang Oil Company Hospital between March 2006 and August 2012 were retrospectively analyzed. All the patients received orbital tumor dissection or biopsy, then received radiation therapy. Three patients received chemotherapy with CHOP protocol before radiotherapy. Radiotherapy was delivered routinely with 3D-conformal radiation therapy (CRT) technique with daily 2-2.5 Gy for 5 times per week and 3-5 fields. Total dosage was 20-50 Gy. There were 18 cases of 30 Gy, 1 case of 22 Gy, 1 case of 25 Gy, 1 case of 20 Gy, 1 case of 28.8 Gy, 3 cases of 40 Gy, 1 case of 42 Gy, 1 case of 46 Gy and 1 case of 50 Gy. Results: All the patients had complete remission (CR) after radiotherapy during follow-up. One patient recurred after radiotherapy of 4 months and received CR with radiotherapy again. One patient died of lung infiltration. Acute complications during radiotherapy were conjunctivitis (28 cases, 100.0%) and keratitis (1 case, 3.6%), long-term complications with ophthalmoxerosis (10 cases, 35.7%) and decreased visual acuity (1 case, 3.6%). Conclusion Radiotherapy is an effective method for primary orbital lymphoma, and the adverse reactions can be tolerated for most patients.

Objective To study the anti-aging effect of total saponins of Polygala tenuifolia (PTS). Methods The effects of total saponins of Polygala tenuifolia on oxygen free radicals were investigated by the methods of scavenging hydroxyl radical, superoxide radical and DPPH oxygen free radicals in vitro. The photoaging model of mice skin was established to observe the effect of total saponins of Polygala tenuifolia on mouse skin pathology. Results In the experiment of antioxidation in vitro, the total saponins of Polygala tenuiflora significantly scavenged hydroxyl free radicals (P<0.05, P<0.001) and superoxide radical (P<0.01) at 6.0 and 12.0mg/mL, DPPH free radicals (P<0.001). In the light aging experiment, the light aging model of mice skin was established successfully in group B (model + medium tea oil). Compared with group B, the density of the skin epidermis in D group (30 min before irradiation, 6mg/mL PTS) was thickened, the elastic fibers were arranged uniformly and tightly, the collagen fibers proliferated significantly and densely, and the inflammatory cells infiltration was not found. The treatment effect was most remarkable in group G (30min after irradiation, PTS 12mg/mL PTS), and the skin of the mice was thickened, the elastic fibers were evenly arranged, the collagen fibers had some hyperplasia, evenly distributed, and there was no infiltration of inflammatory cells, which had significant therapeutic effect. Conclusion The total saponins of Polygala tenuifoliahas significant antioxidant activity and anti - light aging effect.