Objective:To investigate the correlation between blood uric acid level and body composition, exercise capacity, and cardiopulmonary function in medical examination population.Methods:In this cross-sectional study, 83 individuals who underwent physical examinations at Peking University Third Hospital from June 1, 2023, to October 1, 2023, and met the inclusion criteria were included. According to whether they had hyperuricemia (HUA), the participants were divided into HUA group (53 cases) and non-HUA group (30 cases). Body composition parameters, such as body mass index and visceral fat area, were measured with a body composition analyzer. Exercise capacity indicators, including grip strength, vertical jump, back strength, and sit-and-reach test, were measured using specific monitoring devices. Cardiopulmonary function was assessed using the stair index test. The clinical characteristics of the two groups were compared with t-tests or chi-square tests, and the correlation between uric acid levels and body composition, exercise capacity, and cardiopulmonary function was analyzed. Results:The HUA group had significantly higher skeletal muscle mass, body fat mass, body mass index, and visceral fat area when compared with the non-HUA group [(31.92±5.60) vs (26.11±6.19) kg, (23.66±9.33) vs (17.19±5.00) kg, (26.53±3.68) vs (23.27±3.59) kg/m2, 91.20 (74.25, 123.90) vs 68.25 (56.25, 90.48) cm 2, respectively] (all P<0.05). The grip strength, vertical jump, and back pull strength were all lower in the HUA group [32.70 (25.25, 40.30) vs 42.35 (35.95, 48.10) kg, 30.30 (24.10, 36.48) vs 40.55 (33.06, 45.10) kg, 24.20(20.60, 32.23) vs 29.90 (25.20, 35.50) cm, 65.60 (51.75, 78.00) vs 91.00 (67.25, 111.50) kg, respectivley] (all P<0.05). The increased step index was positively correlated with reduced risk of hyperuricemia ( OR=0.875, 95% CI: 0.793-0.966) ( P<0.05). Conclusions:Blood uric acid level is correlated with cardiopulmonary function in medical examination population. Individuals with better cardiopulmonary function have a lower risk of developing HUA. However, the relationship between blood uric acid level and body composition and exercise capacity is not clear.

Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

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 clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

14- to 16-membered macrolide antibiotics (MA) are clinically important anti-infective drugs. With the rapid emergence of bacterial resistance, there is an urgent need to develop novel MA to counter drug-resistant bacteria. The targeted optimization of MA can be guided by analyzing the interaction between the MA and its ribosomal targets, and the desired MA derivatives can be obtained efficiently when combining with the rapidly developed metabolic engineering approaches. In the past 30 years, metabolic engineering approaches have shown great advantages in engineering the biosynthesis of MA to create new derivatives and to improve their production. These metabolic engineering approaches include modification of the structural domains of the polyketide synthase (PKS) and post-PKS modification enzymes as well as combinatorial biosynthesis. In addition, the R&D (including the evaluation of its antimicrobial activities and the optimization through metabolic engineering) of carrimycin, a new 16-membered macrolide drug, are described in details in this review.
Anti-Bacterial Agents ; Bacteria/genetics* ; Macrolides ; Metabolic Engineering ; Polyketide Synthases

INTRODUCTIONStreptococcus agalactiae (Group B Streptococcus, GBS) is an uncommon cause of septic arthritis in the adult population. In recent years, there has been an increase in the incidence of GBS septic arthritis. This study aims to compare the clinical presentation, investigations, microbiology and outcome of management in patients with GBS and non-GBS septic arthritis.

METHODSRetrospective review of hospital surgical records was done to identify all patients treated surgically at our institution from January 2011 to January 2016 for primary septic arthritis. Patients were categorised into two groups: those with culture-proven GBS septic arthritis and those with causative pathogens that were not GBS. Patients who were medically unfit for surgical intervention as well as those who declined interventional procedures were excluded from the study.

RESULTSA total of 83 patients were included in the study: 62 (74.7%) had non-GBS septic arthritis and 21 (25.3%) had GBS septic arthritis. Patients with GBS septic arthritis were more likely to have polyarticular involvement (p < 0.001) and involvement of less common sites such as the elbow joint. They were also more likely to have elevated inflammatory markers (C-reactive protein > 150 mg/L; p = 0.017) and positive blood cultures (p = 0.02), and were typically healthy adults with no medical comorbidities (p = 0.012).

CONCLUSIONPatients with GBS septic arthritis were more likely to present with polyarticular involvement, positive blood cultures and higher levels of C-reactive protein on admission, and tended to be healthier individuals with no medical comorbidities.

Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.

As highly active anti-retroviral therapy continues, large numbers of drug-resistant strains appeared in human immunodeficiency virus ( HIV) infectors, which always leads to a decline of treatment results or even a treatment failure.The genotypic resistance analysis technique of the bioinformatics is a powerful tool to forecast the HIV resistance and also determines the success or failure of antiviral therapy.This review will be focus on the advantages and disadvantages, influence factor of the genotype resistance prediction and improve measure of the primary HIV drug resistance genotype interpretation system, depending on the principle and characteristics of the genotypic drug resistance analysis as the breakthrough point, in order to provide guidance for reasonable application of different genotypes drug resistance analysis system in China.