In recent years， diabetic nephropathy （DN） has become an increasingly serious health challenge worldwide， and its morbidity and mortality rates are rapidly increasing. The patients suffering from the disease tend to be younger. DN is not only accompanied by a wide range of renal pathological changes， such as renal hypertrophy， inflammatory cell infiltration， expansion of the tethered membrane stroma， and thickening of the basement membrane but is also the main cause of end-stage renal disease and death in patients with diabetes mellitus. Therefore， it is particularly urgent to explore new strategies for the prevention and treatment of DN. The pathogenesis of DN is intricate and complex， with current research focusing on multifactorial interactions between metabolic and hemodynamic factors， such as hypoxia， inflammatory responses， and fibrotic processes. Notably， hypoxia plays a pivotal role in the initiation and progression of DN. Hypoxia-inducible factor （HIF-1α）， as a key regulatory protein commonly found in hypoxic cells， has a profound impact on various physiological and pathological processes， such as cell metabolism， vascular neogenesis， oxidative stress， and apoptosis. With its unique theoretical system and therapeutic approach， traditional Chinese medicine has demonstrated significant advantages in coping with hypoxic diseases and can slow down the progression of DN by regulating the expression level of HIF-1α and its downstream signaling molecules and exerting anti-inflammatory， antioxidant， and antifibrotic effects， which has positive clinical significance for drug development and early prevention and treatment of DN.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Medicine, Chinese Traditional ; Atherosclerosis/drug therapy* ; Lipoproteins ; Plaque, Atherosclerotic ; Biomarkers

ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.

Objective To investigate the effects of Rhodojaponin Ⅲ on cartilage injury in post-traumatic osteoarthritis rats and its mechanism.Methods SD rats were randomly divided into sham operation group,model group(based on cruciate ligamentectomy),low dose experimental group(after modeling,0.12 mg·kg-1 Rhodojaponin Ⅲ was given by intragastric administration),high dose experimental group(after modeling,0.24 mg·kg-1 Rhodojaponin Ⅲ was given by intragastric administration),positive drug group(2 mL/100 g glucosamine sulfate was given intragastric administration after modeling).Ten rats in each group were given continuous intragastric administration for 28 days,blood was collected from the heart,and cartilage tissue was taken from the rats.Mankin's score method was used to analyze the cartilage tissue of rats in each group,Western blot method was used to detecte the proteins level,enzyme-linked immunosorbent assay(ELISA)test was used to detect the expression level of serum bone formation indexes and related factors in cartilage tissue,and kit method was used to detect the expression of oxidative stress related indexes.Results The Mankin's scores of sham operation group,model group,low dose experimental group,high dose experimental group and positive drug group were 0.10±0.30,5.30±0.46,4.00±0.63,3.10±0.54 and 1.50±0.81;bone gla protein(BGP)level were(10.25±0.77),(2.39±0.34),(4.87±0.27),(7.99±0.51)and(8.55±0.71)ng·mL-1;the expression levels of cleaved cysteine aspartate proteinase-3(Cl-caspase-3)protein were 0.25±0.02,0.86±0.06,0.65±0.05,0.47±0.04 and 0.33±0.03;superoxide dismutase(SOD)activity were(109.07±7.51),(60.24±5.73),(67.99±4.73),(76.16±8.84)and(80.11±3.96)U·mg-1;the protein levels of nuclear transcription factor E2 related factors(Nrf2)were 1.03±0.08,0.33±0.04,0.43±0.05,0.75±0.10 and 0.74±0.09;heme oxygen-1(HO-1)protein expression levels were 0.88±0.08,0.27±0.04,0.39±0.04,0.56±0.10 and 0.58±0.06,respectively.Model group compared with sham operation group,low dose experimental group,high dose experimental group compared with model group;low dose experimental group compared with high dose experimental group,the differences of the above indexes were all statistically significant(all P＜0.05).Conclusion Rhodojaponin Ⅲ may inhibit oxidative stress,inflammatory response,regulate bone metabolism and improve cartilage injury in post-traumatic osteoarthritis rats by activating Nrf2/HO-1 pathway.

Objective:To analyze the disease burden in middle-aged and elderly population aged ≥55 in Shenzhen from 2016 to 2030 and provide evidence for the development of healthy aging strategies.Methods:The years of life lost (YLL), years lost due to disability (YLD), and the disability-adjusted life year (DALY) in this population from 2016 to 2022 were calculated. Joinpoint log-linear regression model was used to analyze the time trend. Bayesian age-period-cohort model and grey system model were used to predict YLL, YLD, and DALY in this population in 2030.Results:From 2016 to 2022, the crude DALY rate showed a transient fluctuation in age group 55-74 years, but a pronounced increase in age group ≥85 years. The proportions of YLL and YLD due to non-communicable diseases in all age groups was considerably higher than those due to communicable and nutritional diseases and injuries. In 2022, in all age groups, the YLL due to neoplasms (55-74 years old) and cardiovascular disease (≥75 years old) ranked first, and the YLD due to musculoskeletal disorder ranked first. By 2030, the causes of YLL and YLD ranking first in each age group would be remained, while the ranks of some causes would increase.Conclusions:The age specific characteristics of current and predicted disease burden differed in individuals aged ≥55 years. Therefore, it is necessary to allocate social and medical resources according to the disease burden pattern.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.