OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Objective:To examine the associations of BMI and waist circumference (WC) with the risk of chronic kidney disease (CKD) and its subtypes in adults in China.Methods:The data from the China Kadoorie Biobank were used. After excluding those with cancer, coronary heart disease, stroke, or CKD at baseline survey, 480 430 participants were included in this study. Their body height and weight, and WC were measured at baseline survey. Total CKD was defined as diabetic kidney disease (DKD), hypertensive nephropathy (HTN), glomerulonephritis (GN), chronic tubulointerstitial nephritis (CTIN), obstructive nephropathy (ON), CKD due to other causes, and chronic kidney failure. Cox proportional hazards regression model was used to estimate the associations between exposure factors and risks of outcomes.Results:During a follow-up period of (11.8±2.2) years, 5 486 cases of total CKD were identified, including 1 147 cases of DKD, 340 cases of HTN, 1 458 cases of GN, 460 cases of CTIN, 598 cases of ON, 418 cases of CKD due to other causes, and 1 065 cases of chronic kidney failure. After adjusting for socio-demographic factors, lifestyle factors, baseline prevalence of hypertension and diabetes, and WC and compared to participants with normal BMI (18.5-23.9 kg/m 2), the hazard ratios ( HRs) of total CKD for underweight (<18.5 kg/m 2), overweight (24.0-27.9 kg/m 2), and obese (≥28.0 kg/m 2) were 1.42 (95% CI: 1.23-1.63), 1.00 (95% CI: 0.93-1.08) and 0.98 (95% CI: 0.87-1.10), respectively. Stratification analysis by WC showed that BMI was negatively associated with risk for total CKD in non-central obese participants (WC: <85.0 cm in men and <80.0 cm in women) ( HR=0.97, 95% CI: 0.96-0.99), while the association was positive in central obese participants (≥90.0 cm in men and ≥85.0 cm in women) ( HR=1.03, 95% CI: 1.01-1.05). The association between BMI and GN was similar to that of total CKD. BMI was associated with an increased risk for HTN, with a HR of 1.12 (95% CI: 1.06-1.18) per 1.0 kg/m 2 higher BMI. After adjusting for potential confounders and BMI, compared to participants with non-central obesity, the HRs for pre-central obesity (WC: 85.0-89.9 cm in men and 80.0-84.9 in women) and central obesity were 1.26 (95% CI: 1.16-1.36) and 1.32 (95% CI: 1.20-1.45), respectively. With the exception of HTN and CTIN, WC was positively associated with risks for all CKD subtypes. Conclusions:BMI-defined underweight and central obesity were independent risk factors for total CKD, and BMI and WC had different associations with risks for disease subtypes.

Objective:To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) versus functional electrical stimulation (FES) in the treatment of post-stroke complex regional pain syndrome. Methods:The randomized controlled study included 60 patients with post-stroke complex regional pain syndrome who received treatment at the Wenzhou TCM Hospital of Zhejiang Chinese Medical University from July 2021 to February 2023. These patients were divided into an rTMS group ( n = 30) and an FES group ( n = 30) using a random number table method. Patients in the rTMS group were treated with rTMS, while those in the FES group were treated with FES. All treatments were performed once daily for 8 consecutive weeks. The clinical efficacy, total active movement score of the fingers, Fugl-Meyer assessment scale score, Activity of Daily Living score, modified Barthel Index score, shoulder joint range of motion, and safety were compared between the two groups. Results:The total response rate in the FES group was 86.7% (26/30), which was significantly higher than 83.3% (25/30) in the rTMS group ( Z = 0.09, P = 0.93). After treatment, there were no significant differences between the two groups in terms of total active movement score of the fingers and Fugl-Meyer assessment scale score ( P = 0.244, 0.262). No significant differences were found between the two groups in MBI score and ADL score (both P > 0.05). There was also no significant difference in shoulder joint range of motion between the two groups ( P > 0.05). Conclusion:Both rTMS and FES are highly effective for post-stroke complex regional pain syndrome. They can improve upper limb function, enhance daily living abilities, and remodel neurological functions of the brain.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.

In recent years， with the increasing understanding of the genetic mechanisms of hypertrophic cardiomyopathy， novel molecular-targeted drugs Mavacamten and Aficamten are two cardiac myosin inhibitors currently approved by the FDA for the treatment of hypertrophic obstructive cardiomyopathy. Both of them have a similar mechanism of action and can selectively bind to different variable sites of cardiac myosin to inhibit cardiac myosin， thus reducing myocardial hypercontractility. Relevant clinical studies have also shown that both drugs can reduce patients’ left ventricular outflow tract pressure gradient， the levels of N-terminal pro-B-type natriuretic peptide and cardiac troponin I as cardiac markers， and improve New York Heart Association （NYHA） cardiac function class. They are safe， have mild adverse reactions， and can be tolerated by patients. Compared to Mavacamten， Aficamten， as a structurally optimized product， has a shorter half-life and fewer drug-drug interactions， which is more conducive to drug- targeted dose titration.

Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

BACKGROUND: Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted. METHODS: We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored. RESULTS: Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2-5] loci vs. 5 [3-5] loci, P  = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P  = 0.024). On the other hand, those with decreased CD4 + /CD8 + T-cell ratio developed more fever (0.8 [0.7-1.2] vs. 1.4 [1.1-2.2], P  = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932-0.995, P  = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859-0.975, P  = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control. CONCLUSIONS Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.
Humans ; Leukocytes, Mononuclear ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Unrelated Donors ; Granulocyte Colony-Stimulating Factor ; Graft vs Host Disease