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 cognitive function and sleep quality of the elderly in Shanghai community, and explore the related influencing factors. Methods A stratified cluster random sampling method was used to select 8 community health centers in Shanghai for a questionnaire survey, including 3 677 elderly individuals who completed the “Comprehensive Health Status Survey of Elderly Residents in Shanghai” from September 2023 to November 2023. Basic information of the elderly was collected, including age, gender, education level, smoking, drinking, mahjong playing behavior, and exercise habits. The Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of the elderly, subjective cognitive decline (SCD) self-assessment questionnaire and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function, while the Hamilton Anxiety Scale (HAMA) and patient health questionnaire-9 (PHQ-9) were used to assess anxiety and depression levels, and the mini nutritional assessment (MNA) was used to evaluate nutritional status. According to the MMSE scores, the elderly were divided into three groups: no cognitive impairment (MMSE ≥ 27), mild cognitive impairment (MMSE 21-26), and moderate to severe cognitive impairment (MMSE ≤ 20). The general data, lifestyle habits, and scale scores of the three groups were compared. Ordered logistic regression was used to analyze the influencing factors of sleep quality. Results There were statistically significant differences in age, gender, waist circumference, body mass index (BMI), education level, pet ownership, smoking, drinking, mahjong playing behavior, exercise habits, and scale scores among the three groups (P＜0.05). Logistic regression analysis showed that age, waist circumference, gender, drinking habits, mahjong playing behavior, and chronic comorbidities are influencing factors for the PSQI grading in the elderly (P＜0.05). The MMSE score (OR＝1.037, P＝0.001), SCD score (OR＝1.123, P＜0.001), HAMA score (OR＝1.183, P＜0.001), PHQ-9 score (OR＝1.249, P＜0.001) are positive influencing factors for PSQI grading, while the MNA score is a negative influencing factor (OR＝0.960, P＝0.037). Conclusions Advanced age, female gender, low education level, no pet ownership, no mahjong playing behavior, no exercise habits, and poor sleep quality are risk factors for cognitive impairment in the elderly. Advanced age, female gender, no mahjong playing behavior and poor nutritional status are influencing factors for poor sleep quality in the elderly, and severe comorbidities, anxiety, depression, and subjective decline in cognitive function all affect sleep quality.

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 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 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 evaluate the effect of radiotherapy on hypothyroidism (HT) in patients with breast cancer after radical surgery, and to establish a HT prediction model.Methods:Clinical data of 296 patients who received radiotherapy after radical mastectomy and followed up regularly in Affiliated Cancer Hospital of Xinjiang Medical University from January 2015 to May 2023 were retrospectively analyzed. Baseline clinicopathological information was extracted and thyroid dose volume histograms were reviewed to obtain dosimetric parameters such as thyroid volume, thyroid D mean, D min, D max and V 15 Gy-V 50 Gy, etc. The thyroid function levels of all patients were detected before radiotherapy and at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months after radiotherapy, and the incidence of HT after treatment was calculated to determine the effect of radiotherapy on thyroid function. Cox regression model was used for univariate and multivariate analyses to identify the factors associated with HT and establish the predictive model. The optimal cut-off value of influencing factors was calculated by using the receiver operating characteristic curve. The cumulative incidence curve was drawn by Kaplan-Meier method. Inter-group differences were compared by using log-rank test. Results:At a median follow-up of 36 months, HT occurred in 130 patients (43.92%). The peak of HT occurred approximately 12 (9-18) months after radiotherapy. Univariate analysis showed that neoadjuvant chemotherapy ( HR=1.736, 95% CI=1.222-2.467, P=0.002), thyroid D min ( HR=1.001, 95% CI=1.001-1.001, P<0.001) and thyroid D mean ( HR =1.001, 95% CI=1.001-1.002, P<0.001) were the risk factors for HT. Multivariate analysis showed that thyroid D mean was correlated with the occurrence of HT ( HR=1.001, 95% CI=1.001-1.001, P=0.002). The optimal cut-off value of thyroid D mean was 2771.66 cGy, and the incidence of HT was statistically different between high-risk group (D mean>2771.66 cGy) and low-risk group (D mean≤2771.66 cGy) ( P<0.001). Conclusions:Radiotherapy after radical surgery is associated with the occurrence of HT in patients with breast cancer. Minimizing the thyroid D mean below 2771.66 cGy is an effective method to protect thyroid function. It is recommended to start monitoring thyroid function no later than 9 months after radiotherapy in patients receiving neoadjuvant chemotherapy.

Objective:To investigate the current status of clinical practice of optical surface guided radiation therapy (SGRT) technology in China.Methods:A survey questionnaire was designed based on a similar investigation conducted by the European Society for Radiotherapy and Oncology in collaboration with the American Association of Physicists in Medicine on SGRT. The questionnaire covered aspects such as the installation, implementation, commissioning, quality assurance, clinical application, challenges, and cost considerations of SGRT systems. An online questionnaire was distributed to 49 institutions in China that have installed or are in the process of installing SGRT systems. Data were summarized and analyzed using Excel and SPSS 29 software.Results:Among the 49 institutions, 96% had at least one SGRT system. In terms of commissioning, quality assurance and implementation, it was mainly operated by physicists (94%) and technicians (82%), the cycle of test items for quality assurance was only achieved by the highest percentage of units with end-to-end test items for the annual inspection (50%). Eighty-six percent of the institutions used phantoms provided by suppliers, and 53% followed supplier recommendations or guidelines. For the installation of the first SGRT system, 37% of the institutions reported that initial staff training required more than 48 hours, while 73% found the training content easy to understand. Regarding the clinical application of SGRT technology, the majority of the institutions (53%) had used it for 1-3 years, with breast radiotherapy being the most commonly used treatment site. The primary scenario of SGRT application was intra-fraction motion monitoring / patient monitoring (69%). Furthermore, 47% of the institutions combined SGRT with open-face masks, and 71% used visual feedback devices for breath-hold or free-breathing gating. In terms of treatment thresholds, the median thresholds for monitoring and positioning were the same for breast, abdominopelvic (non- stereotactic body radiation therapy), and head-and-neck (non-brain stereotactic radiosurgery) treatments but varied for other sites.Conclusions:Although SGRT technology requires a relatively long initial training period, it is generally well accepted in terms of training and operation. Clinically, SGRT has been widely applied in breast radiotherapy, playing a crucial role in patient monitoring and intra-fraction motion management. However, most institutions have had limited clinical experience with the technology, highlighting the need for continuous technical supervision and improvement. The establishment of standardized protocols is necessary to ensure broader clinical adoption and long-term effectiveness.

Objective To retrospectively analyze the changes in cerebral blood flow(CBF)of hippocampus before and after radiotherapy(RT)and to explore its relationship with dose for providing a feasible approach for dynamically monitoring hippocampal response after whole brain radiation therapy in patients with brain metastases(BMs).Methods A retrospective analysis was conducted on magnetic resonance(MR)images from 43 BMs patients before and after RT,including T1-weighted imaging(T1WI)and three-dimensional arterial spin labeling(3D-ASL)imaging.Manual segmentation of the hippocampal structures was performed on T1WI to determine hippocampal volume,while CBF within the hippocampus was derived from 3D-ASL images.Patients were categorized into different groups according to the time interval between two MR scans and the dose received by the hippocampus,namely short time interval[<30 d,with an average of(19.74±7.15)d]≤1 Gy,1-30 Gy and≥30 Gy groups;long time interval[>3 months,with an average of(495.50±226.06)d]≤1 Gy,1-30 Gy and≥30 Gy groups.The patterns of changes in hippocampal CBF and volume,as well as the dose-effect relationship following RT were analyzed.Results(1)A total of 86 hippocampi were enrolled,showing reductions of 8.32%in minimum CBF(CBF-min),7.31%in maximum CBF(CBF-max),8.09%in mean CBF(CBF-mean),and 4.11%in hippocampal volume after RT(P<0.05).The decrease rates of CBF-min,CBF-max and CBF-mean were 6.33%,7.01%and 8.23%higher than the reduction rate of hippocampal volume,respectively.(2)With a brief interval between two MR simulation localization scans,hippocampal CBF in the groups receiving≤1 Gy and 1-30 Gy exhibited an increase,with the increase rate positively correlated to the radiation dose absorbed by the hippocampus.Conversely,in the group receiving≥30 Gy,hippocampal CBF decreased.The variations in the rate of hippocampal CBF change across the dose groups were statistically significant,except when comparing≤1 Gy and 1-30 Gy groups(P<0.05).Additionally,the hippocampal volume in all 3 dose groups experienced a slight increase,with the growth rate also positively correlated to the radiation dose received by the hippocampus;however,these differences were not statistically significant(P>0.05).(3)With a long interval between MR simulation localization scans,both hippocampal CBF and volume in all 3 dose groups demonstrated decreasing trends,with the decrease rate positively correlated to the radiation dose received by the hippocampus.Statistically significant differences in the rate of CBF change were noted among the dose groups,except for the comparison between≤1 Gy and 1-30 Gy groups(P<0.05).The reduction rate of hippocampal volume across 3 dose groups was statistically significant(P<0.05).Conclusion The reduction in hippocampal CBF following RT in BMs patients is more sensitive than the reduction in hippocampal volume,exhibiting a pronounced dependence on both time and radiation dose.Consequently,CBF changes should be employed as a standard bioindicator for monitoring the response to hippocampal RT and predicting radiological injuries after whole brain radiotherapy in BMs patients.