ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

Objective To explore the effects of image registration using various regions of interest(ROI)on the setup error for nasopharyngeal carcinoma(NPC)patients who were immobilized individually.Methods Forty-three NPC patients who required radiotherapy were enrolled.The patients were immobilized with customized plastic foam and thermoplastic mask,and CBCT verification was performed once a week.In CBCT images,ROI was divided into the whole ROI(ROIPTV)and 7 local ROI containing different cervical structures(ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,ROIneck4,ROIneck5,ROIneck6,and ROIneck7),which were then used for registrations with localized CT image.The setup errors in superior-inferior(SI),left-right(LR),anterior-posterior(AP),Pitch,Roll,and Yaw directions were recorded.Results In SI direction,the setup errors within 0.3 cm accounted for 89.74%for ROIneck7,and more than 90%for the other ROI.The proportion of setup errors within 0.3 cm gradually increased with the neck upward in LR direction,and they were 76.78%,81.70%,85.26%,and above 90%for ROIneck7,ROIneck6,ROIneck5,and the other ROI,respectively.In AP direction,the proportions of setup errors within 0.3 cm were less than 90%,except for ROIatlantoaxial and ROIneck3.The setup errors of ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,and ROIneck4 were significantly positively correlated with ROIPTV in SI direction,and the correlation coefficients(R)were 0.94,0.95,0.90,and 0.83,respectively.In LR direction,there were positive correlations between the setup errors of ROIatlantoaxial and ROIsphenoid sinus(R=0.95),ROIneck3 and ROIsphenoid sinus(R=0.91),ROIPTV and ROIneck3(R=0.91).The setup errors of ROIPTV in AP direction were positively correlated with ROIatlantoaxial vertebrae and ROIneck3(R=0.88,0.90).The margins of all ROIs ranged from 0.38 cm to 1.01 cm.The extension of ROIneck6 and ROIneck7 in AP direction exceeded 0.9 cm,and the extension of ROIneck7 reached 0.95 cm in SI direction.Conclusion ROIPTV and ROIsphenoid sinus,ROIatlantoaxial,ROIneck3 are significantly correlated in SI,LR,and AP directions.The setup error of nasopharyngeal carcinoma patients gradually increases with the neck down.The nasopharyngeal and cervical regions need to be expanded in segments when patients are immobilized individually.

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti–tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To observe the effects of transnasal humidified rapid-insufflation ventilatory exchange(THRIVE)on gastric air intake and SpO2 in patients with painless endoscopic mucosal resection(EMR)of colorectal polyps.Methods Seventy patients with painless colorectal polyps EMR,36 males,34 females,aged 18-64 years,BMI 18-25 kg/m2,ASA Ⅰ or Ⅱ.The patients were divided into two groups:high-flow oxygen inhalation group(group T)and conventional oxygen inhalation group(group C)by random number table method,35 cases in each group.Patients in group T were given THRIVE oxygen inhalation,and patients in group C were routinely inhaled oxygen through the nose.During anesthesia,the BIS value was maintained at 50-65.Bedside gastric ultrasonography was used to observe the gastric content and gastric air intake of patients.The HR and resting SpO2 in the supine position were recorded 5 minutes before the surgery(rest for 5 minutes),1 minute after entering the endoscope,when entering the endoscope to the ileocecal valve,and at the end of the surgery.The PaCO2,PaO2 and pH values were recorded 5 mi-nutes before surgery,when entering the endoscope to the ileocecal valve,and at the end of the surgery,so were gastric intake and satiety,and antral cross-sectional area(CSA)for 5 minutes before surgery and after surgery.The occurrence of mild,moderate,and severe hypoxia during anesthesia were recorded.The opera-tion time,the amount of propofol used during the operation,the number of dosage times of remifentanil,PACU residence time,and infusion during surgery,the occurrence of adverse reactions such as hypotension,hypertension,bradycardia,reflux aspiration,postoperative nausea and vomiting,and the sat-isfaction score of digestive endoscopy physicians and patients were recrded.Results Compared with group C,SpO2 in group T was significantly increased 1 minutes after entering the endoscope(P＜0.05),and PaCO2 was significantly decreased at the time of entering the endoscope to the ileocecal valve and the end of the surgery(P＜0.05),the incidence of mild and moderate hypoxia was significantly reduced in group T(P＜0.05).No positive gastric air intake and full stomach were found in both groups at rest for 5 minutes and after the surgery.There was no significant difference in the incidence of adverse reactions and patient satisfaction scores between the two groups.The satisfaction score of endoscopists in group T was significantly higher than that in group C(P＜0.05).Conclusion Compared with conventional nasal catheter oxygen inhalation,THRIVE ventilation does not cause hypercapnia or affect gastric intake and stomach content,does reduce the occurrence of mild to moderate hypoxia in patients undergoing painless EMR,does not in-crease the risk of reflux aspiration,and has a higher satisfaction of digestive endoscopy physicians.

Background and Objectives: Adipose-derived stem cell (ADSC) transplantation improves stem cell paracrine function and can enhance wound healing. However, in diabetic patients, glucose-associated effects on this function and cell survival lead to impaired wound closure, thereby limiting ADSC transplantation efficiency. The hypoxia-inducible factor HIF-1α has an important protective function during wound healing. Here, we aim to clarify the regulatory mechanism of ADSCs. Methods: and Results: ADSCs were isolated from BALB/C mice adipose samples. We then used high-throughput se-quencing to assess abnormal expression of circular RNAs (circRNAs). We also used an in vivo full-thickness skin defect mouse model to assess the effects of transplanted ADSC on diabetic wound closure. Hypoxic pretreatment of ADSCs accelerated diabetic wound closure, which enhanced angiogenic growth factor expression in our mouse model. High-throughput sequencing and RT-qPCR indicated that circ-Gcap14 was upregulated in hypoxic pretreated ADSCs. Similarly, circ-Gcap14 downregulation also decreased the therapeutic effects of ADSCs; however, circ-Gcap14 overexpression increased the effects of ADSC by promoting angiopoiesis. We also used a luciferase reporter assay to confirm that miR-18a-5p and HIF-1α were downstream targets of circ-Gcap14. HIF-1α expression plays an important role in increased VEGF level. Conclusions Based on our data, we suggest that circ-Gcap14 plays an important role in accelerating hypoxic ADSC-mediated diabetic wound closure, by enhancing mouse angiogenic growth factor expression and regulating downstream miR-18a-5p/HIF-1α expression.

The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown. This study aimed to investigate this association in a community-dwelling population aged ≥ 40 years in Shanghai, China. Oral glucose tole3rance test was conducted during baseline and follow-up visits. Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk. A total of 613 (10.3%) incident diabetes cases were identified during the follow-up visit after 4.5 years. Fasting plasma glucose, postload glucose, and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid (all Ps < 0.05). The incidence rate of diabetes increased across the quartiles of serum uric acid (7.43%, 8.77%, 11.47%, and 13.43%). Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid (odds ratio (95% confidence interval) = 1.36 (1.06-1.73)). Stratified analysis indicated that the association was only observed in women. Accordingly, serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.
Adult ; Aged ; China/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Uric Acid

Objective To investigate the association between levels of serum alanine aminotransferase (ALT) and the risks of cardiovascular disease in Chinese. Methods A survey of 10 375 subjects aged 40 or older in Jiading District of Shanghai was performed using cluster sampling. All the subjects were recruited to undergo questionnaire interview, anthropometric measurements, and fasting blood sampling. A total of 8 877 participants were included in the final analyses, including 5 664 females and 3 213 males. The mean age of individuals was ( 58.68 ± 9.22)yearsinmenand(57.65±8.93)yearsinwomen(P＜0.01).10-yearriskforafirsthardatherosclerotic cardiovascular diseases (ASCVD) event was calculated. Results Increased ALT levels were associated with more unfavorable cardiovascular risk profiles and 10-year risk for ASCVD. Increased ALT levels were associated with the prevalence of diabetes mellitus in female participants, while in male participants the prevalence of diabetes mellitus appeared as a U-distribution. The prevalence of hypertension and hyperlipidemia were 66.04%, 52.74%and 64.49%, 47.63% respectively. Increased serum ALT was associated with higher prevalence of 10-year risk for ASCVD. As compared with participants in the first ALT quartile, the risks of 10-year risk for ASCVD were increased by 148%(OR＝2.48, 95%CI 1.78-3.45) and 139%(OR＝2.39, 95%CI 1.78-3.19), respectively in male and female participants. As compared with participants in the first ALT quartile, higher prevalence of 10-year risk for ASCVD were increased by 96%(OR＝1.96, 95%CI 1.30-2.95), while there was no significantly statistical difference in men. Conclusion A high-normal serum ALT level was significantly associated with an increased risk of the cardiovascular disease in middle-aged and elderly Chinese.

Objective To explore the effect of the expressive psychotherapy on the feeling of inadequacy and loneliness of inpatients with chronic schizophrenia.MethodsTotally 120 chronic schizophrenia inpatients met recruited criteria were randomly divided into study group(n=60) and control group(n=60) according to random number table.57 patients in each group finished all the follow-ups finally.The patients in two groups were received normal medications while the patients in intervention group also attended expressive psychotherapy.All the patients were assessed at baseline,6 weeks and 12 weeks of treatment with the feeling of inadequacy scale (FIS) and the status and trait loneliness scale (STLS).Results(1) The FIS score(F=225.19,P<0.01),STLS total score(F=225.20,P<0.01),STLS status score(F=240.40,P<0.01) and STLS trait score(F=106.75,P<0.01) decreased significantly in both groups after intervention.(2) The FIS score of study group was much lower than those of control group at the at 6-week-follow-up(4.93±20.86,57.89±20.48,t=-2.250,P<0.01) and 12-week-follow-up(38.43±17.50,57.21±22.98,t=-4.900,P<0.01).(3) After 6 weeks treatment and 12 weeks treatment,STLS total score(6 weeks:(54.32±12.30) vs (68.46±15.53),t=-5.425,P<0.01,12 weeks:(44.16±10.81) vs (65.75±16.26),t=-8.386,P<0.01),STLS status score (6 weeks:(25.95±6.41) vs (34.31±7.91),t=-6.239,P<0.01,12 weeks:(19.15±5.49) vs (32.58±8.45),t=-10.103,P<0.01) and STLS trait score (6 weeks:(28.37±6.73) vs (34.15±8.45),t=-4.138,P<0.01,12 weeks:(25.00±6.18) vs (33.15±8.22),t=-6.019,P<0.01) in study group were lower than those in control group,and the difference was statistically significant.ConclusionExpressive psychotherapy can effectively improve the loneliness and inadequacy of patients with chronic schizophrenia.

Objective To analyze the serotypes and antimicrobial susceptibility profile of Group B Streptococcus (GBS) in perinatal pregnant women.Methods The vaginal and rectal specimens were collected from pregnant women at 35 to 37 weeks of pregnancy for culture and identification.The serotypes were analyzed using agglutination assay.Antimicrobial susceptibility testing was conducted by using Kirby-Bauer method,and interpreted according to 2009 CLSI breakpoints.The data were analyzed via WHONET 5.6 software.Results The prevalence of GBS was 10.4％ (264/2 533) in the 2 533 perinatal pregnant women.Serotype Ⅲ,Ⅰa and Ⅰb was identified in 54.9％ (84/153),17.6％ (27/153) and 13.1％ (20/153) of the GBS,respectively.All the GBS isolates were susceptible to penicillin,cefiriaxone and vancomycin.But 32.9％,68.1％ and 62.1％ of the isolates were resistant to levofloxacin,erythromycin and clindamycin,respectively.The antibiotic resistance rate of serotype Ⅲ isolates to the above three antibiotics was significantly higher than the other serotypes.Conclusions GBS may colonize both vagina and rectum of pregnant women.Vaginal and rectal secretions should be sampled simultaneously for better screening GBS.GBS serotype Ⅲ was the predominant serotype.Penicillin can be used as the first-choice treatment for GBS infections in pregnant women and newborns.GBS-positive pregnant women should be given the intervention treatment immediately to ensure the health of perinatal infants.