This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

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Hiatal hernia (HH) refers to a common digestive system disorder in which the stomach or other abdominal organs protrude into the thoracic cavity through the esophageal hiatus.With changes of people's lifestyles,accelerated aging,and rising rates of obesity and overweight,the incidence of HH in China has been steadily increasing.Early diagnosis and accurate classification of HH are critical for guiding treatment decisions. Conventional diagnostic methods-such as barium swallow X-ray,gastroscopy,computed tomography,and high resolution esophageal manometry-have limitations,including invasiveness,radiation exposure,high costs,or inadequate dynamic assessment.Gastric contrast-enhanced ultrasound,as a novel non-invasive imaging technique,has demonstrated unique advantages in the evaluation of HH in recent years.This article reviews the technical principles,clinical applications,and recent advancements of gastric contrast-enhanced ultrasound.
Humans ; Hernia, Hiatal/therapy* ; Contrast Media ; Ultrasonography ; Stomach/diagnostic imaging*

Objective To investigate the clinical effect of unilateral percutaneous vertebroplasty(PVP)combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.Methods A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study,all of which were vertebral body compression fractures caused by trauma.According to different treatment methods,they were di-vided into experimental group and control group.Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group,there were 5 males and 27 females,aged from 63 to 91 years old with an average of(77.59±8.75)years old.Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty,including 7 males and 38 females,aged from 60 to 88 years old with an average of(74.89±7.37)years old.Operation time,intraoperative C-arm X-ray times,anesthetic dosage,bone cement injection amount,bone cement diffusion good and good rate,complications,vertebral height,kyphotic angle(Cobb angle),visual analogue scale(VAS),Oswestry disability index(ODI)and other indicators were recorded before and after surgery,and statistically analyzed.Results All patients were followed up for 6 to 23 months,with preoperative imaging studies,confirmed for thoracolumbar osteoporosis com-pression fractures,two groups of patients with postoperative complications,no special two groups of patients'age,gender,body mass index(BMI),time were injured,the injured vertebral distribution had no statistical difference(P＞0.05),comparable data.Two groups of patients with bone cement injection,bone cement dispersion rate,preoperative and postoperative vertebral body height,protruding after spine angle(Cobb angle),VAS,ODI had no statistical difference(P＞0.05).The operative time,intra-operative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P＜0.05).Compared with the traditional bilateral puncture group,the modified unilateral puncture group combined with 3D printing technology had shorter operation time,fewer intraoperative fluoroscopy times and less anesthetic dosage.The height of anterior vertebral edge,kyphosis angle(Cobb angle),VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P＜0.05).Conclusion In the treatment of thoracolumbar osteoporotic compression fractures,3D printing technology is used to improve unilateral puncture PVP,which is convenient and simple,less trauma,short operation time,fewer fluoroscopy times,satisfactory distribution of bone cement,vertebral height recovery and kyphotic Angle correction,and good functional improvement.

Objective: To determine the nutritional status and associated factors of vitamin D in primary and middle school students in Shandong Province, so as to provide reference for developing targeted vitamin deficiency interventions. Methods: From January to September 2021, using multi stage stratified random sampling, physical examinations and laboratory tests were carried out among 3 539 primary and middle school students in Shandong Province. Associated factors of vitamin D were analyzed by Logsitc regression analysis. Results: The average vitamin D level among primary and middle school students was (17.56±6.65) ng/mL, while the deficiency and severe deficiency rate was 67.4%. Multivariate Logistic regression analysis showed that girls ( OR =1.95), students in junior high school ( OR =2.14) and senior high school ( OR =2.36) were at higher risk of vitamin D deficiency and severe deficiency ( P <0.05). Students from coastal areas ( OR =0.54), physical examination in summer and autumn ( OR = 0.74 ), and 35 g of egg intake per day ( OR =0.53), and with outdoor activity time greater than 60-120 min and >120 min ( OR =0.63, 0.48) had lower risk of vitamin D deficiency ( P <0.05). Conclusions The nutritional status of vitamin D among elementary and secondary school students in Shandong Province warrants further attention. Intervention measures such as nutritional education, healthy diet and prolonging outdoor activities should be promoted in primary and middle school students.

At present, brain disease has become a "killer" in the field of general health, and the existence of blood-brain barrier has become one of the challenges in drug delivery into the brain. According to studies, cell membrane coating technique can endow nanoparticles with the characteristics of immune escape, long circulation, targeted delivery, and so on. Therefore, membrane biomimetic nanoparticles have been widely used in the field of disease treatment. Among them, the cell membrane derived from immune cells, tumor cells, and stem cells can cross the blood-brain barrier through the transcellular pathway and cell bypass pathway, which is used to prepare biomimetic membrane nanoparticles to break through the blood-brain barrier to achieve the treatment of brain diseases. What's more, the brain targeted ability of biomimetic nanoparticles would be further enhanced by modifying the cell membrane with peptides. This paper introduces the preparation methods of membrane biomimetic nanoparticles, expounds in detail the way that cell membrane coated nanoparticles break through the blood-brain barrier and achieve efficient intracerebral drug delivery. It also summarizes the prospects and challenges of this novel drug delivery system in the treatment of brain diseases, providing a reference for the research of membrane biomimetic nanoparticles in the treatment of brain diseases.

Objective To evaluate the malaria diagnostic capability in Shanghai Municipal Malaria Diagnostic Reference Laboratory from 2017 to 2022 and to analyze factors affecting the diagnosis results, so as to provide the scientific evidence for increasing the laboratory malaria diagnostic capability during the post-elimination stage. Methods Plasmodium-negative blood smears were randomly sampled using a proportional sampling method each quarter during the period from 2017 to 2022 and scored by Shanghai Municipal Malaria Diagnostic Reference Laboratory. Malaria cases’ blood samples from district centers for disease control and prevention in Shanghai Municipality were re-reviewed using microscopy and multiplex PCR assay to evaluate the capability of malaria diagnosis. Results A total of 7 746 quality control blood smears were collected from district centers for disease control and prevention in Shanghai Municipality from 2017 to 2022, with a mean score of (76.74 ± 14.34) points and a qualification rate of 86.65% (6 712/7 746). A total of 387 blood smears were re-reviewed from 2017 to 2022, with an overall coincidence of 96.38% (373/387) for malaria diagnosis and 95.06% (308/324) for parasite species identification, and there were no significant differences in the coincidence for either malaria diagnosis (χ² = 2.57, P > 0.05) or parasite species identification among years (χ² = 1.04, P > 0.05). A total of 384 whole blood samples were collected from district centers for disease control and prevention, and the detection of whole blood samples was 70.31% (270/384) in district centers for disease control and prevention. All 384 whole blood samples were re-reviewed by Shanghai Municipal Malaria Diagnostic Reference Laboratory using a multiplex PCR assay from 2017 to 2022, with an overall coincidence of 94.07% (254/270) for malaria diagnosis and 99.55% (223/224) for parasite species identification, and there were no significant differences in the coincidence for either malaria diagnosis (χ² = 5.77, P > 0.05) or parasite species identification among years (χ² = 8.37, P > 0.05). The overall coincidence rates of Plasmodium-positive and negative whole blood samples were 100.00% (224/224) and 65.22% (30/46) in district centers for disease control and prevention, with a significant difference (χ² = 82.82, P < 0.001), and there was a significant difference in the coincidence rate for identification of P. falciparum, P. vivax, P. malariae and P. ovale (χ² = 24.28, P < 0.001). A total of 1 584 blind blood smears subjected to microscopic examinations by centers for disease control and prevention and medical institutions across all districts in Shanghai Municipality from 2017 to 2022, with a 96.15% (1 523/1 584) correct rate for malaria diagnosis and 85.07% (1 003/1 179) for parasite species identification, and there were significant differences in the correct rate of both malaria diagnosis (χ² = 20.98, P < 0.001) and parasite species identification among years (χ² = 70.77, P < 0.001). A total of 320 blind nucleic acid samples from malaria cases were tested, with a 99.38% (318/320) correct rate for malaria diagnosis and 100.00% (225/225) for parasite species identification, and there was no significant difference in the correct rate of malaria diagnosis among years (χ² = 6.04, P > 0.05). Conclusions There were still shortcomings in blood smears preparation, microscopic examinations and nucleic acid testing in centers for disease control and prevention across all districts in Shanghai Municipality from 2017 to 2022. A greater role in the quality control of malaria diagnosis is recommended for Shanghai Municipal Malaria Diagnostic Reference Laboratory to prevent the re-establishment of imported malaria and consolidate the elimination achievements.

Objective:To compare the clinical characteristics and changes in inhaled drugs of newly diagnosed chronic obstructive pulmonary disease (COPD) patients in some hospitals in Hunan and Guizhou from 2017 to 2023, in order to further understand the current status of COPD diagnosis and treatment.Methods:This cross-sectional study included stable COPD patients who were initially diagnosed in the respiratory and critical care departments of 13 hospitals in China from January 1, 2017 to December 31, 2023. They were divided into 7 groups based on the time of their initial visit: the 2017, 2018, 2019, 2020, 2021, 2022, and 2023 groups. Basic information of the patients, the percentage of forced expiratory volume per second (FEV 1% pred), FEV 1/forced vital capacity (FVC), COPD assessment questionnaire (CAT) scores, the number of acute weightings in the past year, and inhalation drug regimens were collected. Results:The CAT scores of patients with COPD who visited from 2017 to 2019 were significantly higher than those from 2020 to 2023 (all P<0.05); The FEV 1% pred and FEV 1/FVC of patients with COPD showed an increasing trend from 2017 to 2023; The proportion of patients using long-acting muscarine anticholinergic (LAMA) gradually decreased between 2017 and 2023, with 8.0% (134/1 665) of patients with COPD using single drug LAMA in 2023. The proportion of patients using double branch dilators has been increasing year by year in 2018, 2019, 2020, and 2021, and the proportion of patients using double branch dilators for COPD has stabilized in 2021, 2022, and 2023, with no statistically significant difference between groups ( P>0.05). The proportion of patients with COPD who used triple inhalation drugs was the lowest in 2020 and 2021 ( P<0.05). In 2017, 2018, 2019, 2022, and 2023, the proportion of patients with COPD who used triple inhalation drugs was 45.2%(364/806), 54.0%(730/1 352), 55.5%(742/1 337), 45.8%(717/1 565), and 51.1%(851/1 665), respectively. The compliance with inhalation prescriptions and Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) documents for newly diagnosed patients with COPD from 2017 to 2023 was 47.9%(386/806), 35.1%(474/1 352), 33.7%(451/1 337), 40.3%(405/1 005), 31.2%(372/1 193), 28.4%(445/1 565), and 58.8%(979/1 665), respectively. Conclusions:With the migration of time, the clinical symptoms of newly diagnosed COPD patients have been alleviated, indicating a trend of forward shift in treatment time; The proportion of double bronchodilators used has increased, and the proportion of triple inhaled drugs used is relatively high. The compliance with GOLD documents is still not ideal.