ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog （PTEN）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups （n=8 each group）： model group， miR‑21 overexpression group， miR‑21 inhibition group， and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression， miR‑21 inhibition， and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus （50 μL， 1×10⁸ TU per mouse） once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector （LV‑NC）. The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 （480 mg/kg） once weekly for three weeks. The expressions of miR‑21， 24 h urinary protein， serum creatinine （Scr）， blood urea nitrogen （BUN）， and renal tissue levels of collagen Ⅰ， collagen Ⅲ， α‑smooth muscle actin （α‑SMA）， and PTEN protein， as well as p‑AKT/AKT and p‑mTOR/mTOR ratios， were compared among groups. HE staining was used to observe pathological changes in renal tissue， and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group， miR‑21 expression in renal tissue increased in the miR‑21 overexpression group （P<0.05） and decreased in the miR‑21 inhibition group （P<0.05）. Compared with the model group， the miR‑21 overexpression group showed increased 24 h urinary protein， Scr， BUN， and renal tissue expression of collagen Ⅰ， collagen Ⅲ， and α‑SMA （all P<0.05）， while these indicators decreased in the miR‑21 inhibition group （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein， Scr， BUN， and renal tissue expression of Collagen Ⅰ， Collagen Ⅲ， and α‑SMA （all P<0.05）. Compared with the model group， the miR‑21 overexpression group showed decreased PTEN protein expression （P<0.05） and increased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， while the miR‑21 inhibition group showed increased PTEN expression （P<0.05） and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement， capillary loop adhesion， and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure， accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis， with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1， the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased （P<0.001）. There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.

Objective:To explore the effect of combining intensive laryngeal elevation training with repeated transcranial magnetic stimulation (rTMS) based on the concept of " central-peripheral-central" (CPC) on dysphagia in stroke survivors.Methods:Eighty stroke survivors with dysphagia were selected and randomly divided into a control group, a lift group, an rTMS group and a combination group, each of 20. In addition to neurologic drug therapy and routine swallowing training, the lift group received intensive throat elevation training, the rTMS group received rTMS, while the combination group underwent both before and after 4 weeks of treatment, all were evaluated using video swallowing angiography (VFSS), a leakage-aspiration scale (PAS) and a functional oral feeding scale (FOIS).Results:After the treatment, the average VFSS, PAS and FOIS scores had improved significantly in all 4 groups, with those of the lift group, the rTMS group and the combination group then significantly better than the control group′s averages. The combination group′s scores were significantly better than those of the other 3 groups. There was no significant difference in any of the indexes between the lift and TMS groups.Conclusions:CPC-based intensive laryngeal ascent training combined with rTMS can significantly improve the swallowing of stroke survivors with dysphagia in convalescence.

Objective To investigate the impact of pomegranate peel polyphenols(PPP)on the malignant biological behavior of colon cancer cells through modulation of the miR-138-5p/hypoxia-inducible factor-1α(HIF-1α)pathway.Methods Quantitative real-time PCR(qRT-PCR)was employed to measure the expression levels of miR-138-5p and HIF-1α mRNA in the normal colon epithelial cell line FHC and three colorectal cancer cell lines:SW480,HCT116,and Caco-2.SW480 cells were divided into six groups:a blank control group,a negative control(mimics NC)group,a miR-138-5p mimics group,three different concentrations of PPP treatment groups(0.5 mg/mL,1 mg/mL,and 2 mg/mL),a PPP+inhibitor NC group at 2 mg/mL,and a PPP+miR-138-5p inhibitor group at 2 mg/mL.The effects on cell proliferation,invasion,and migration,as well as changes in apoptosis and related proteins including B-cell lymphoma 2(Bcl-2),migration invasion enhancer 1(MIEN1),and Cyclin D1,were evaluated separately.Additionally,the targeting relationship between miR-138-5p and HIF-1α was validated.The expression levels of miR-138-5p,HIF-1α mRNA,and protein were assessed in each experimental group.Results The expression levels of miR-138-5p were highest in FHC cells and lowest in SW 480 cells,while the expression levels of HIF-1α mRNA showed an opposite trend,being lowest in FHC cells and highest in SW 480 cells(P<0.05).Compared with the control group,different concentrations of PPP significantly promoted cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein,with significant differences between groups(P<0.05).Compared with the mimics NC group,the miR-138-5p mimics group significantly enhanced cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).Compared with the 2 mg/mL PPP+inhibitor NC group,the 2 mg/mL PPP+miR-138-5p inhibitor group significantly suppressed cell apoptosis,downregulated miR-138-5p expression,promoted cell proliferation,invasion,and migration,and upregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).These results indicate a targeted relationship between miR-138-5p and HIF-1α(P<0.05).Conclusion PPP inhibits the malignant biological behavior of colon cancer cells through upregulation of the miR-138-5p/HIF-1α pathway.

Objective To explore relationship between glucose metabolism and neonatal weight in high-risk gestational diabetes melli-tus(GDM).Method A retrospective study was conducted on 779 pregnant women who underwent prenatal examinations at Tongzhou Maternity and Child Health Care Hospital in Beijing from March to June 2022.The data on pre-pregnancy weight,mid-and late-preg-nancy glycated albumin(GA)and glycated hemoglobin(HbA1c),pre-delivery weight,gestational weight gain,and neonatal birth weight were collected.A GDM risk assessment model was established using multivariate logistic regression to classify pregnant women into high-risk and low-risk groups for GDM,followed by separate management strategies.Regression discontinuity(RD)analysis was applied to evaluate the relationship between gestational glucose metabolism status and neonatal birth weight.Results Among the 779 pregnant women,the overall incidence of macrosomia was 7.32％.The high-risk GDM group exhibited significantly higher pre-pregnan-cy weight,late-pregnancy HbA1c,and GA levels compared to the low-risk group(all P＜0.001).Neonatal birth weight in the high-risk group was significantly higher than that in the low-risk group(P＜0.05),with a significantly increased macrosomia incidence(13.55％vs 5.77％,P＜0.05).RD analysis revealed a jump reduction of 199.59 g(P=0.029)in neonatal birth weight at the risk score thresh-old.Conclusion Lifestyle glucose metabolism management in high-risk GDM pregnant women may effectively reduce neonatal birth weight,mitigated the trend of excessive gestational weight gain,and improved late-pregnancy HbA1c and GA levels,providing evi-dence-based support for maternal and child health services.

OBJECTIVE To investigate the epidemiological characteristics of hospital-associated infections caused by multidrug-resistant organisms(MDROs)among the burn wound patients so as to provide bases for taking tar-geted control measures.METHODS A systematic search was conducted in the worldwide database for nosocomial outbreaks,PubMed and CNKI databases so as to summarize and analyze the data regarding to outbreaks of MDROs hospital-associated infections among burn wound patients.RESULTS A total of 61 incidents of MDROs hospital-associated infections outbreaks among the burn wound patients were included,involving 2 293 patients from 21 countries and regions,50(81.97％)of which were reported for the infection sites or colonization sites in-volving burn wound,12(19.67％)involving the respiratory tract,10(16.39％)involving the bloodstream infec-tions.Methicillin-resistant Staphylococcus aureus(28 incidents,45.90％)was dominant among the pathogens causing the infections,followed by multidrug-resistant Acinetobacter baumannii(17 incidents,27.87％)and multidrug-resistant Pseudomonas aureus(9 incidents,14.75％).52 incidents(82.25％)of outbreaks were reported the contact as the major transmission mode.The suspected sources of the outbreaks included the patients(37 incidents,28.46％),health care workers(30 incidents,23.08％),ward environments(28 incidents,21.54％),medical equipments(19 incidents,30.56％),drainage systems(6 incidents,4.62％).The major pre-vention and control measures included environmental cleaning and disinfection,screening of colonization in patients and health care workers,isolation of patients with infections and hand hygiene;8 incidents were taken the measure of closing the ward.CONCLUSIONS The outbreaks of MDROs infections in the burn wound patients are mostly associated with the high frequently contact environments,medical equipments and hand hygiene of health care workers.In view of the peculiarities of the burn wound patients,it is feasible to take the targeted measures based on the summarized prevention and control combinations for MDROs so as to prevent the outbreak of hospital-asso-ciated infections.

Objective:To explore the effect of combining intensive laryngeal elevation training with repeated transcranial magnetic stimulation (rTMS) based on the concept of " central-peripheral-central" (CPC) on dysphagia in stroke survivors.Methods:Eighty stroke survivors with dysphagia were selected and randomly divided into a control group, a lift group, an rTMS group and a combination group, each of 20. In addition to neurologic drug therapy and routine swallowing training, the lift group received intensive throat elevation training, the rTMS group received rTMS, while the combination group underwent both before and after 4 weeks of treatment, all were evaluated using video swallowing angiography (VFSS), a leakage-aspiration scale (PAS) and a functional oral feeding scale (FOIS).Results:After the treatment, the average VFSS, PAS and FOIS scores had improved significantly in all 4 groups, with those of the lift group, the rTMS group and the combination group then significantly better than the control group′s averages. The combination group′s scores were significantly better than those of the other 3 groups. There was no significant difference in any of the indexes between the lift and TMS groups.Conclusions:CPC-based intensive laryngeal ascent training combined with rTMS can significantly improve the swallowing of stroke survivors with dysphagia in convalescence.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.