Background Prior epidemiological studies suggest that exposure to pyrethroid insecticides may adversely affect children’s respiratory health. However, only limited studies are currently available on this topic in China. Objective To explore the association between exposure to pyrethroid insecticides and pulmonary function in children in Shanghai. Methods From August 2019 to January 2020, a cross-sectional study was conducted, recruiting 163 healthy school-aged children (aged 5–12 years) from Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine. Basic information, including age, height, weight, and family income, was collected. Urine samples from the children were collected and were analyzed for the levels of three pyrethroid insecticide metabolites: 3-phenoxybenzoic acid (3-PBA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA). Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used for the analysis. Spirometry was used to assess pulmonary function and recorded following parameters: peak expiratory flow (PEF), forced expiratory flow between the 25th and 75th percentiles of forced vital capacity (FEF_25-75), forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC. Multiple linear regression and restricted cubic spline models were used to evaluate the associations between urinary pyrethroid insecticide metabolite levels and pulmonary function parameters. Results The study included 163 school-aged children, with an average age of (7.04 ± 2.08) years and an average body mass index (BMI) of (16.04 ± 2.72) kg·m⁻²; 75 (46.01%) of the participants were boys. The detection rates of 3-PBA, TDCCA, and CDCCA in urine were 85.28%, 17.79%, and 4.91%, respectively. The median creatinine-adjusted 3-PBA concentration was 0.150 μg·g⁻¹. After adjusting for confounders such as height, BMI, sex, age, delivery mode, annual family income, and maternal education level, the multiple linear regression model showed that urinary 3-PBA levels were negatively associated with both FVC [β=−0.030, 95% confidence interval (CI): −0.058, −0.003; P=0.031] and FEV₁ (β=−0.032, 95%CI: −0.064, 0.000; P=0.04998). The final restricted cubic spline model showed a nonlinear association between urinary 3-PBA levels and FVC, FEV₁, PEF, and FEF_25-75（P for nonlinear < 0.05；P for overall < 0.05）. Conclusion The level of pyrethroid insecticide exposure in school-aged children in Shanghai is relatively high. The urinary 3-PBA concentration is negatively associated with pulmonary function, indicating potential adverse effects of pyrethroid insecticide exposure on respiratory health of school-aged children.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective:To observe the clinical and imaging features of patients with retinal vein occlusion (RVO) complicated with retinal artery occlusion (RAO).Methods:A retrospective clinical study. Fifteen patients with 15 eyes with RVO combined with RAO and macular edema diagnosed by ophthalmology examination in the Department of Ophthalmology, First People's Hospital of Xianyang City during 2 years from February 1, 2022 to January 31, 2024 were included in the study. Branch retinal vein occlusion (BRVO) combined with branch retinal artery occlusion (BRAO) occurred in 3 cases and 3 eyes. Central retinal vein occlusion (CRVO) complicated with central retinal artery occlusion (CRAO) in 12 eyes. Best corrected visual acuity (BCVA), intraocular pressure, scanning laser ophthalmoscope, optical coherence tomography (OCT), fluorescein fundus angiography (FFA) and serum homocysteine were all performed. OCT angiography (OCTA) was performed in 6 eyes. All eyes were treated with intravitreal injection of anti-vascular endothelial growth factor drugs. After the initial 1 treatment, dosage was assessed as needed. Follow-up was performed every month for 12 months after treatment. FFA inspection was performed at 3 months. During follow-up, it was found that there were no perfusion areas of capillaries, and retinal laser photocoagulation therapy was given in time. Fundus manifestations, FFA, OCT, OCTA characteristics and causes of disease were analyzed retrospectively.Results:There were 15 eyes in 15 cases, 9 eyes in 9 males; 6 women with 6 eyes. Age was (61.0±9.7) years. All complained of painless vision loss in one eye. All eyes were positive for relative afferent pupillary disorder. Contralateral congenital optic disc defect was in 1 case; hypertension was in 6 cases; hyperhomocysteinemia was in 2 cases; cerebral infarction was in 3 cases; coronary heart disease was in 1 case. CRVO combined with CRAO was in 12 eyes BCVA light sensitivity-0.25. The BCVA of BRVO combined with BRAO were 0.1, 0.4 and 0.25, respectively. All the patients had retinal edema in the posterior pole of the eye, venous sinuous, dilated, thin arteries and stiff shape. The retina presents with flaky or flame-like bleeding. Posterior polar retinal lint patch was in 13 eyes. In 12 eyes with CRVO combined with CRAO, optic disc edema was observed and the boundary was not clear. In 3 eyes with BRVO combined with BRAO, no obvious abnormality was found in the optic disc, and the boundary was clear. FFA examination showed no or prolonged arterial filling, delayed retinal vein laminar flow, relatively slow or even no capillary filling, macular arteriole atretosis to varying degrees, arch ring structure destruction, optic disc telangiectasia and fluorescein leakage. OCT examination showed that the middle and inner layers of the retina were thickened to varying degrees, the diffuse reflex was enhanced, the interlayer structure was unclear, and the reflex of the lower retinal tissue was weakened. The blood flow density of superficial capillary plexus and deep capillary plexus (DCP) decreased in 6 eyes undergoing OCTA examination. Decreased or interrupted blood flow in the vascular bed of DCP. During the follow-up period, there were 13 eyes with no perfusion area of retinal capillary. The time of occurrence was (1.14±0.95) (0-2) months, and the area was 10-75 disc area. Optic nerve atrophy occurred in 5 eyes. At the last follow-up, visual acuity increased, unchanged and decreased in 12, 2 and 1 eyes, respectively.Conclusions:The pathogenesis of RVO-RAO is complicated. Most RVO and RAO occurred simultaneously, and a few RVO occurred several days after RAO. Although the RAO manifestations are not typical, the radiographic features are both RVO and RAO. Compared with BVRO combined with BRAO, the prognosis of visual acuity in CRAO patients with CRVO is worse.

Objective: To investigate the serum anti-mumps IgG antibody levels among children aged 0 to 4 years in Haishu District, Ningbo City, Zhejiang Province, so as to provide insights into improvements for mumps vaccination program. Methods: Children aged 0 to 4 years were sampled from Haishu District using a stratified random sampling method in 2016 (before adjustment of the mumps vaccination program) and 2022 (after adjustment of the mumps vaccination program). Participants' demographics were collected using questionnaires, and the coverage of mumps-containing vaccines was collected from the Ningbo Municipal Immunization Information System. Serum anti-mumps IgG antibody was measured using enzyme-linked immunosorbent assay (ELISA), and the seroprevalence of anti-mumps IgG antibody and geometric mean concentration (GMC) were estimated among children aged 0 to 4 years in 2016 and 2022. Results: A total of 464 children were enrolled in 2016, including 250 boys (53.88%) and 214 girls (46.12%), and there were 301 children receiving mumps-containing vaccines (64.87%). The seroprevalence of anti-mumps IgG antibody were 48.08%, 34.44%, 81.11%, 84.44% and 84.44%, and GMC were 233.86, 351.77, 333.66, 362.29 and 410.72 U/mL. A total of 456 children were recruited in 2022, including 236 boys (51.75%) and 220 girls (48.25%), and there were 427 children receiving mumps-containing vaccines (93.64%). The seroprevalence of anti-mumps IgG antibody were 72.73%, 95.00%, 100.00%, 98.68% and 99.04%, and GMC were 524.05, 1 229.69, 1 623.64, 788.01 and 738.41 U/mL. Higher seroprevalence and GMC of anti-mumps IgG antibody was seen in 2022 than in 2016 among children at all age groups (P<0.05). Conclusion Following adjustment for vaccination programs, the seroprevalence and GMC of anti-mumps IgG antibody significantly increased among children at ages of 0 to 4 years in Haishu District.

Objective: To investigate the incidence of microvascular myocardial ischemia in diabetic patients without obstructive coronary artery disease (CAD) and its relationship with angina. Materials and Methods: Diabetic patients and an intermediate-to-high pretest probability of CAD were prospectively enrolled. Non-diabetic patients but with an intermediate-to-high pretest probability of CAD were retrospectively included as controls. The patients underwent dynamic computed tomography-myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) to quantify coronary stenosis, myocardial blood flow (MBF), and extracellular volume (ECV). The proportion of patients with microvascular myocardial ischemia, defined as any myocardial segment with a mean MBF ≤ of 100 mL/min/100 mL, in patients without obstructive CAD (Coronary Artery Disease–Reporting and Data System [CAD-RADS] grade 0–2 on CCTA) was determined. Various quantitative parameters of the patients with and without diabetes without obstructive CAD were compared. Multivariable analysis was used to determine the association between microvascular myocardial ischemia and angina symptoms in diabetic patients without obstructive CAD. Results: One hundred and fifty-two diabetic patients (mean age: 59.7 ± 10.7; 77 males) and 266 non-diabetic patients (62.0 ± 12.3; 167 males) were enrolled; CCTA revealed 113 and 155 patients without obstructive CAD, respectively. For patients without obstructive CAD, the mean global MBF was significantly lower for those with diabetes than for those without (152.8 mL/min/100 mL vs. 170.4 mL/min/100 mL, P < 0.001). The mean ECV was significantly higher for diabetic patients (27.2% vs. 25.8%, P = 0.009). Among the patients without obstructive CAD, the incidence of microvascular myocardial ischemia (36.3% [41/113] vs. 10.3% [16/155], P < 0.001) and interstitial fibrosis (69.9% [79/113] vs. 33.3% [8/24], P = 0.001) were significantly higher in diabetic patients than in the controls. The presence of microvascular myocardial ischemia was independently associated with angina symptoms (adjusted odds ratio = 3.439, P = 0.037) in diabetic patients but without obstructive CAD. Conclusion Dynamic CT-MPI + CCTA revealed a high incidence of microvascular myocardial ischemia in diabetic patients without obstructive CAD. Microvascular myocardial ischemia is strongly associated with angina.

Acute intermittent porphyria(AIP) is a rare inherited metabolic disease that can cause severe and fatal acute attacks. This article shares the treatment and management of a severe AIP patient. It is proposed that (1) avoiding incentives is essential; (2) emotional problems easily overlooked should be paid attention; (3) long-term follow-up and patient education can improve the prognosis. The patient underwent renal biopsy during the remission period. We found a red-brown-yellow-white refractive index crystal under a polarized light microscope that had not been reported in the previous literature, which was speculated to be a porphyrin crystal.

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
Nucleic Acids/chemistry* ; Regenerative Medicine ; Consensus ; Reproducibility of Results ; DNA/chemistry*