Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011-2014.

Background: Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether Se can mitigate the adverse effects of cadmium (Cd) and lead (Pb) on hand grip strength (HGS) in middle-aged and elderly individuals. Methods: This study used data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). HGS measurements were conducted by trained examiners with a dynamometer. Concentrations of Se, Cd, and Pb in blood were determined via inductively coupled plasma mass spectrometry. We employed linear regression, restricted cubic splines, and quantile g-computation (qgcomp) to assess individual and combined associations between heavy metals and HGS. The study also explored the potential influence of Se on these associations. Results: In both individual metal and multi-metal models adjusted for confounders, general linear regression showed Se's positive association with HGS, while Cd and Pb inversely related to it. At varying Se-Cd and Se-Pb concentrations, high Se relative to low Se can attenuate Cd and Pb's HGS impact. An inverted U-shaped correlation exists between Se and both maximum and combined HGS, with Se's benefit plateauing beyond approximately 200 µg/L. Stratified analysis by Se quartiles reveals Cd and Pb's adverse HGS effects diminishing as Se levels increase. Qgcomp regression analysis detected Se alleviating HGS damage from combined Cd and Pb exposure. Subsequent subgroup analyses identified the sensitivity of women, the elderly, and those at risk of diabetes to HGS impairment caused by heavy metals, with moderate Se supplementation beneficial in mitigating this effect. In the population at risk for diabetes, the protective role of Se against heavy metal toxicity-induced HGS reduction is inhibited, suggesting that diabetic individuals should particularly avoid heavy metal-induced handgrip impairment. Conclusion: Blood Cd and Pb levels are negatively correlated with HGS. Se can mitigate this negative impact, but its effectiveness plateaus beyond 200 µg/L. Women, the elderly, and those at risk of diabetes are more vulnerable to HGS damage from heavy metals. While Se supplementation can help, its protective effect is limited in high diabetes risk groups.

[Comparison of therapeutic effect of soft-tissue relaxing needling and electroacupuncture for knee osteoarthritis].

OBJECTIVE: To compare the clinical efficacy of soft-tissue relaxing needling and electroacupuncture (EA) in the treatment of knee osteoarthritis (KOA), so as to explore a new and more effective therapy for KOA. METHODS: Forty patients with KOA who met our diagnostic criteria were randomly and equally divided into acupuncture group and soft-tissue relaxing needling (relaxing-needling) group. EA (20 Hz, a tolerable strength and duration of 20 min) was applied to the unilateral Neixiyan(EX-LE5) and Waixiyan(EX-LE5), and manual acupuncture stimulation was applied to Heding(EX-LE2), Xuehai (SP10), Xiyangguan (GB33), Liangqiu(ST34), Yanglingquan(GB34) and Yinlingquan(SP9) on the affected side by using uniform reinforcing-reducing technique. In the relaxing-needling group, after identifying the tender point and nodule-like or stiff-strip-muscle spot at the affected limb by palpation, we used filiform needles to insert into them, then, made a longitudinal separation or point-like pricking. The visual analog scale (VAS) pain score, knee flexion activity (range of motion, ROM), and the knee osteoarthritis severity (Lequesne index, composed of daily living, walking distance and pain) were measured before and after the treatment. The therapeutic effect was assessed by consulting the Guiding Principles for Researching New Drugs of Traditional Chinese Medicine (2002) and Criteria for Diagnosis and Assessment of Therapeutic Effect of Syndromes or Illnesses of Traditional Chinese Medicine (1994). RESULTS: After the treatment, the VAS score and Lequesne index were significantly decreased in both acupuncture and relaxing-needling groups (P<0.001), and the ROM score was considerably increased in both groups in comparison with their own pre-treatment (P<0.001). The difference values of VAS score and Lequesne index between pre- and post-treatment were significantly higher in the relaxing-needling group than in the acupuncture group (P<0.05). Of the two 20 cases in the relaxing-needling and acupuncture groups, 8 and 3 experienced a remarkable improvement in their symptoms, 10 and 13 were effective, 2 and 4 failed, with the effective rate being 90.0% and 80.0%, respectively. No significant difference was found between the two groups in the difference value of ROM score and the effective rate (P>0.05)．. CONCLUSION: Both relaxing-needling and EA therapies are comparable in the therapeutic effect for KOA, and the former is superior to the latter in reducing the joint pain and improving the knee joint locomotor function, thus being worthy of clinical application.

Pterostilbene Ameliorates Nephropathy Injury in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Our study investigated the therapeutic role and potential mechanisms of pterostilbene (PS) in diabetic nephropathy (DN) rats. METHODS: DN models were established by high-fat diet after streptozotocin injection. A total of 50 Sprague-Dawley rats were randomly divided into control, DN, PS-treated groups (PS-H, PS-M, PS-L). PS was administered to rats by gavage for 8 weeks at 3 different doses (25, 10, and 5 mg/kg/day). The levels of oxidative stress activity (superoxide dismutase [SOD], malondialdehyde [MDA], glutathione peroxidase [GSH-PX]) and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin (IL)-6, IL-1ß, monocyte chemoattractant factor [MCP]-1) were detected by -ELISA. TGF-ß, Smad1, and fibronectin (FN) were measured through immunohistochemistry. The relative expressions of phospho-IκBα/IκBα, phospho-IκB kinases (IKK)ß/IKKß, phospho-nuclear factor-κB (NF-κB) p65/NF-κB p65 were detected by western blot. RESULTS: Compared with DN group, the levels of TNF-α, IL-6, IL-1ß, and MCP-1 were decreased in the PS-H group (p < 0.05). Meanwhile, the levels of SOD, MDA, GSH-PX improved in kidney and serum in PS-H groups (p< 0.05). PS also significantly decreased the level of phospho-NF-κB p65 and increased the levels of phospho- IKKß and phospho-Iκ-Bα (p < 0.05). The results showed that PS treatment decreased TGF-ß, Smad1, and FN expressions. CONCLUSION: PS had potential therapeutic effects on DN, which may be related to the regulation of NF-κB pathway.