Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress / 药学学报

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion / 药学学报

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Down-regulation of METTL5 inhibits proliferation, migration and invasion of triple-negative breast cancer cells through Wnt/6-catenin signaling pathway / 中国药理学通报

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

Moral Dilemma and Research on Coping Style of Frontline Nurses During the Outbreak of COVID -19 / 中国医学伦理学

【Objective:】 To understand the moral dilemma, coping style of frontline nurses and their correlation during the COVID -19. 【Methods:】 From March to April, 2021, 651 nurses working in designated hospitals for COVID -19 were selected by convenient sampling, and the Chinese version of Moral Distress Scale-Revised (MDS-R) and Chinese version of Coping Style Questionnaire (CSQ) were used for investigation. 【Results:】 Frontline nurses’ MDS-R score was 91.0, "value conflicts" was the moral dilemma with the highest frequency and intensity, more than half (51.0%) of the respondents had considered leaving their position because of moral dilemma. "Problem solving" and "seeking for help" were the major coping strategies adopted by the nurses. Nurses who directly provide medical services for COVID -19 patients, dissatisfied with hospital-related training and adopted negative coping strategies had higher moral dilemmas than other nurses. 【Conclusion:】 The moral dilemma of frontline nurses is at a high level during the period of epidemic prevention and control. Nursing managers should pay attention to guiding and helping nurses to establish positive coping styles and improve their ability to respond to major public health emergencies.

Case observation of viral keratitis caused by SARS-CoV-2 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To report three cases of viral keratitis caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).METHODS: Slit lamp, intraocular pressure, corneal fluorescence staining, anterior segment photography, in vivo confocal microscopy(IVCM), and routine fundus screening were performed in the three confirmed patients. Treatment involved Ganciclovir, artificial tears and glucocorticoid eye drops.RESULTS: Three patients with SARS-CoV-2 keratitis(SCK)recovered well after standard treatment.CONCLUSION: SARS-CoV-2 keratitis typically presents as corneal subepithelial infiltration and can result in a decrease in corneal subepithelial nerve fiber density and an increase in dendritic cells(DC). Antiviral therapy in combination with glucocorticoid has proven to be effective.

Establishment and application of a prospective follow-up research method for acute infectious diseases in Shanghai community residents / 上海预防医学

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Dihydroartemisinin Suppresses Proliferation of Oral Squamous Cell Carcinoma Cells by Promoting Autophagy / 肿瘤防治研究

Objective To investigate the effect of dihydroartemisinin (DHC) on the proliferation capacity of human oral squamous carcinoma cells and its mechanism of action. Methods The viability and colony formation ability of CAL27 cells treated with different concentrations of dihydroartemisinin was measured by CCK-8 and colony formation assay. The expression of proteins related to proliferation and autophagy was determined by Western blot. Potential targets for DHA inhibition of the biological behavior of oral cancer were screened based on network pharmacology and bioinformatics. Measurement was conducted after the cells were cotreated with autophagy blocker 3-methyladenine and autophagy inducers rapamycin and dihydroartemisinin. Results Dihydroartemisinin significantly reduced the proliferation viability and clone formation ability of CAL27 cells in a concentration-dependent manner. The PCNA expression level also decreased substantially. DHA suppressed oral cancer targets involving autophagy-related pathways. DHA intervention increased the expression of intracellular autophagy-related proteins Beclin-1 and LC3. After co-treatment of DHA combined with autophagy blocker, the proliferation viability and clone formation ability of CAL27 cells decreased. The expression of PCNA increased, and the expression of Beclin-1 and LC3 decreased. Conclusion Dihydroartemisinin could inhibit the proliferative capacity of oral squamous carcinoma cells in vitro, and its effect may be correlated with the induction of autophagy.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Hypercalin B alleviates nonalcoholic steatohepatitis progression via suppressing mTORC1 signaling pathway / 药学学报

The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.

Gut microbiota as a target for traditional Chinese medicine in the treatment of cardiovascular disease: potential mechanisms and therapy strategies / 药学学报

Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Effect of aerobic pedal exercise on sleep quality and energy metabolism of female college students with mild sleep disorder / 中国学校卫生

Objective@#To explore the intervention effect of aerobic step exercise on sleep quality of female college students, so as to provide a new perspective to improve the sleep quality of female college students.@*Methods@#In the 2020 fall semester, a total of 41 female college students with mild or more severe sleep disorders were selected from Beijing Normal University through a questionnaire and were randomly divided into experimental group ( n =29) and control group ( n =12). The experimental group received 55 minutes/time step aerobic exercise intervention for 8 weeks, three times a week, while the control group received no exercise intervention from October to December. The two groups maintained the original learning and living habits, without additional physical activity. The Pittsburgh Sleep Quality Index Scale and portable sleep monitor were used to assess the subjects sleep quality from both subjective and objective aspects. Changes in energy metabolism were observed by triaxial accelerometer and standing body composition analyzer.@*Results@#After exercise intervention, subjective sleep quality factor (1.24±0.43, 0.86±0.58), sleep efficiency factor (0.66±0.67, 0.07±0.25), sleep disorder factor (1.24± 0.51 , 1.03±0.18), daytime dysfunction factor (1.90±0.86, 1.48± 0.82 ) and PSQI score (7.21±1.85, 5.66±2.09) significantly improved ( t=3.64, 4.63, 2.27, 2.36, 3.29, P <0.05). The ratio of sleep to wakefulness decreased (25.54±7.86, 20.85± 5.13), the ratio of deep sleep (31.79±12.20, 38.32±10.19) and sleep efficiency (73.99±7.91, 78.68±5.12) increased significantly ( t=-2.12, -2.39, -2.21, P <0.05). Lean body mass [(38.55±2.95, 39.07±2.94)g] and basal metabolic rate [(1 257.45±41.14, 1 262.66 ±42.22)kcal] of the experimental group significantly increased after the intervention of medium high intensity aerobic pedal exercise ( F=5.95, 3.49, P <0.05). Total energy expenditure was positively correlated with subjective sleep quality and sleep efficiency ( r=-0.26, -0.44, P <0.05).@*Conclusions@#The 8 week aerobic step exercise intervention can increase the daytime energy consumption and basic metabolism of female college students. Improve the sleep depth and efficiency of female college students, reduce sleep disorders, and then effectively improve sleep quality.

FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.

Treatment of intravesical instillation with fulguration-hydrodistention on female interstitial cystitis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC).@*METHODS@#Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes.@*RESULTS@#A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05).@*CONCLUSION@#Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.

Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis / 中国中药杂志

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.

Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review / 中国中药杂志

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Effect of standardized training of rehabilitation therapists in Beijing based on rehabilitation competency framework / 中国康复理论与实践

ObjectiveTo analyze the effect of standardized training on post competency of rehabilitation therapists, based on World Health Organization rehabilitation competency framework (RCF), and combined with the characteristics of rehabilitation and the requirements of standardized training in China. MethodsFrom 2018 to 2022, a total of 30 rehabilitation therapists who participated in the standardized training were selected. Before and after the standardized training, the closed-book theoretical assessment and Mini-clinical Evaluation Exercise (Mini-CEX) assessment were carried out, and a 360-Degree Evaluation scale was distributed to their teachers, peers and patients. Through multi-dimensional post competency analysis, the data obtained from the scales were combined with the five dimensions of basic theoretical knowledge, clinical practice ability, medical humanities literacy, scientific research and teaching ability, and organizational management ability to analyze the effect of standardized training on post competency of rehabilitation therapists. ResultsAfter training, the therapists improved in theory and case analysis (Z > 2.716, P < 0.05). They also improved in medical interview skills, physical examination, humane care/professionalism, clinical judgment ability and overall clinical level (Z > 2.162, P < 0.05) according to Mini-CEX. The medical ethics, daily work, management ability, social ability, interpersonal communication ability, basic professional ability and operation ability improved (Z > 1.978, P < 0.05) according to the 360-Degree Evaluation scale. The effect of standardized training was significant in basic theoretical knowledge, clinical practice ability and medical humanities literacy by the post competency analysis model. ConclusionThe effect of standardized training of rehabilitation therapists is significant, and the therapists can be competent for daily work in diagnosis and treatment after training.

Evaluation of the effect of repeated local fluoride application on the prevention of new caries in 3-year-old children with active caries / 上海预防医学

ObjectiveTo evaluate the caries prevention effect of different fluoride application frequencies in 3-year-old children with active caries. MethodsA total of 337 3-year-old children with dental caries from 12 kindergartens in Changning District of Shanghai were divided into three groups： group 1 received fluoride application once every three months， group 2 received fluoride application once every six months， and the control group received no fluoride application. At baseline， parents completed a questionnaire survey， and oral examinations were conducted at baseline， 7 months， and 16 months after the fluoride intervention to assess the incidence of new dental caries， new dmft， and new dmfs of children. Multivariate logistic regression analysis was used to analyze the relationship between fluoride application and new dental caries， with new dental caries as the dependent variable and local fluoride application， child's gender， age in months， parents' highest education level， frequency of sugary intake （desserts， candies， sweet beverages）， age of toothbrushing initiation， frequency of daily toothbrushing， use of fluoride toothpaste， parental assistance in child’s toothbrushing， and daily use of dental floss as the independent variables. ResultsThere were no significant differences in baseline general conditions and oral health behaviors among group 1 （121 cases）， group 2 （123 cases） and the control group （93 cases） （all P>0.05）. After 16 months' intervention， three children were lost to follow-up due to transferring schools. The new caries rates of group 1 （120 cases）， group 2 （121 cases） and the control group （93 cases） were 5.83%， 24.79% and 52.69%， respectively. The incidence of new caries was significantly lower in group 1 compared to group 2 and the control group （P<0.001）， and it was also significantly lower in group 2 compared to the control group （P<0.001）. The newly-increased caries of group 1， group 2 and the non-fluoride control group were all 0.12 0.52， 0.36 0.68 and 1.16 1.39， respectively. The mean increment of new caries was lower in group 1 compared to group 2 （P=0.040） and the non-fluoride control group （P<0.001）， and it was lower in group 2 compared to the non-fluoride control group （P<0.001）. After adjusting for factors such as gender， parents' education level and child's oral health behaviors by multivariate logistic regression， the results showed that fluoride application once every three months could significantly reduce the risk of dental caries （OR=0.04， P<0.001）. ConclusionLocal use of fluoride has a certain effect on the prevention and treatment of dental caries in children with active caries. Fluoride application once every three months effectively reduces the incidence of new caries and slows down the progression of caries lesions. It is suggested that local application of fluoride should be implemented once every three months for children with active caries.