Colorectal cancer is a malignant tumor that originates from the epithelial cells of the colon and rectum. It has the third highest incidence and the second highest mortality rate among malignant tumors worldwide. With the rapid development of the economy and the increasing Westernization of dietary habits in China， its incidence in China has been rising year by year. Over the past decade， despite the introduction of numerous treatment methods for colorectal cancer， the efficacy of existing therapies remains unsatisfactory. In recent years， traditional Chinese medicine （TCM） has become a major focus in the treatment of colorectal cancer due to its advantages of multi-target， multi-pathway mechanisms and low toxicity and side effects. Vascular endothelial growth factor （VEGF） is an important angiogenic factor that promotes blood vessel formation， providing nutrients and oxygen for tumor growth. It also increases vascular permeability， allowing tumor cells to easily pass through the blood vessel wall into other tissues， thereby facilitating metastasis. Several studies have shown that TCM can inhibit tumor angiogenesis and lymphangiogenesis， promote tumor cell apoptosis， and inhibit the proliferation of colorectal cancer cells by acting on the VEGF signaling pathway， thereby delaying tumor growth. In recent years， research in this field has been rapidly updated， but there is a lack of relevant summaries， making subsequent literature searches inconvenient. Therefore， this article focuses on the physiological functions of the VEGF signaling pathway， its role in the occurrence of colorectal cancer， and the intervention of TCM on VEGF， providing a supplement and summary of relevant information to offer a reference for future research in this area.

Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.

“Burnt needle” and “red-hot needling” are both mentioned in the Inner Canon of Yellow Emperor （《黄帝内经》）， although they possess distinct characteristics and are not identical. Subsequent generations have erroneously employed them as interchangeable with “fire needles”， which is an incorrect designation. This article mostly relies on the original text of the Inner Canon of Yellow Emperor and provides an interpretation of their significances as follows： “burnt needle” is a broad phrase referring to needles that have been intentionally burned in order to heat them； the term “burnt needle and rapid needling” can be more accurately described as “the act of rapidly puncturing with a needle， without burning the needle if the disease exhibits hot characteristics， but requiring burning if the disease exhibits cold characteristics， and it is appropriate to puncture rapidly before burning the needle”. “Red-hot needling” refers to the process of first burning the needle and then puncturing with it， which is specific. This paper clarified the origins and differences among burnt needles， red-hot needling， red-hot needle， burning needle， warm needles and fire needle， pointing out the doctrinal diagnostic and therapeutic system based on “burnt Needle” and “red-hot needling”， can be a track for the integration of acupuncture and moxibustion.

OBJECTIVE To establish the analysis methods of 33 banned pesticides in Ginkgo Biloba leaves and the extracts, and conduct the risk assessment study. METHODS One hundred and thirty-six batches of Ginkgo Biloba leaves and 58 batches of Ginkgo Biloba leaves extract were detected by UPLC-MS and GC-MS. The acute and chronic intake risk of pesticide residues in samples were calculated by point assessment method, and the risk scores of the pesticides were calculated by the Britain veterinary residues matrix ranking. RESULTS Six kinds of banned pesticides were detected in 136 batches of Ginkgo Biloba leaves, the total detection rate was 35.29%, and the detection amount was 0.002−0.210 mg·kg−1. The chronic dietary intake risk was 0.018%−0.620%, and the acute dietary intake risk was 0.000 1%−0.014 0%, indicated that the dietary exposure risk of pesticides in Ginkgo biloba leaves was at a low level. Two kinds of banned pesticides were detected in 58 batches of Ginkgo Biloba leaves extract, the detection rate was 55.17%, and the detection amount was 0.002−1.788 mg·kg−1. The percentage of acceptable daily intake was 0.003%−0.143%, and the percentage of acute reference dose was 0.002 4%, which was also at a low level. Risk ranking results indicated that the risk of phorate was the highest and should be focused on the production and safety supervision. CONCLUSION The method has good stability, high precision and promising repeatability, which can be used for the detection of 33 prohibited pesticides in Ginkgo biloba leaves and their extracts. The results show that the residual amounts of 33 banned pesticides in Ginkgo Biloba leaves and its extracts were extremely low, and there is no significant health risks.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

In recent years，with the change in lifestyle and social environment and the increase in pressure in both life and work，male fertility has decreased significantly in China，and the incidence of male infertility has increased year by year，which has brought great challenges to andrologists. Traditional Chinese medicine （TCM） has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility，the China Association of Chinese Medicine （CACM） invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia，abnormal semen liquefaction，varicocele，immune infertility，improving success ratio of assisted reproductive technology，and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages，characteristics，disadvantages，diseases responding specifically，and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility，western medicine cannot achieve a good curative effect，while TCM，taking the holistic view as the core，specializes in improving functional diseases and can correspond to multiple targets and factors，with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists，increase mutual learning and communication between TCM and western physicians，provide patients with excellent and personalized treatment plans in clinical practice，and improve the curative effect of male infertility and fertility of males in China.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective:To understand the sales characteristics and salt iodine content in urban and rural salt market of Guizhou Province.Methods:In accordance with the "Guizhou Province 2020 Iodine Deficiency Disorders Monitoring Field Technical Guidance Work Program", 14 counties (cities, districts) from 88 counties (cities, districts) of 9 cities (states) in Guizhou Province were selected in August 2020. Each county (city, district) selected the urban area and a representative township, and at least 2 supermarkets were selected from the urban area, and 5 supermarkets or retail stores from the townships as the investigation sites, to collect the label information of all commercially available salt within the scope of investigation. At the same time, salt samples were collected after excluding the same brand, variety, and specification, and salt iodine was detected by redox titration.Results:A total of 107 labels of commercially available salt were collected, involving 21 brands, of which Biyuan brand had the largest number (53 samples, 49.5%) and the widest sales range, involving 12 counties (cities, districts). Salt producing areas came from 13 provinces, and the salt produced in Sichuan Province was the most widely distributed in the surveyed area (36 samples), followed by Chongqing Municipality (17 samples) and Hubei Province (16 samples). There were 19 brands (75 samples) and 7 brands (32 samples) of salt sold in urban and rural areas, respectively, and the main brand was Biyuan, accounting for 38.7% (29/75) and 75.0% (24/32), respectively. There were 8 brands (27 samples) and 16 brands (80 samples) of salt sold in retail stores and supermarkets, respectively, and the main brand was Biyuan, accounting for 66.7% (18/27) and 43.8% (35/80), respectively. Among 107 salt samples, it was found that the labeled iodine content did not meet the Guizhou Province salt iodization implementation standard (21 - 39 mg/kg), and only 39 samples (36.4%) had electronic anti-counterfeiting traceability codes on their labels. After excluding the same brand, variety, and specification, the median salt iodine of the 51 salt samples was 23.6 mg/kg, ranging from 19.2 to 38.1 mg/kg, and 21 - 39 mg/kg accounted for 96.1% (49/51).Conclusions:There are many salt brands sold in urban and rural areas in Guizhou Province, and the electronic traceability platform needs to be improved. Salt iodine is mainly distributed in the low-value area of the standard range, which brings potential risks to the sustainable and effective prevention and control of iodine deficiency disorders.

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.
Humans ; Rats ; Animals ; Benzhydryl Compounds/toxicity* ; Phenols/toxicity* ; Auditory Perception/physiology* ; Neurons/physiology*

Objective:To analyze the distribution and drug resistance of wound pathogenic microorganisms in outpatients of wound healing center so as to provide a basis for the standardized construction of wound healing centers.Methods:A retrospective case series study was used to analyzed the data of 365 outpatients treated at Ruijin Hospital, Shanghai Jiaotong University School of Medicine from December 2017 to October 2019. There were 220 males and 145 females, aged (58.8±18.9)years (range, 18-98 years). The patients included 92 first-visit patients and 273 re-visit patients. The culture results (positive rate of pathogenic microorganisms, bacterial species, bacterial distribution) and drug sensitivity results of the wound secretions were compared and analyzed.Results:(1) Among 365 samples of wound secretions, 198 patients were positive for pathogenic microorganisms with a positive rate of 54.3%. A total of 107 strains (51.0%) of Gram-positive bacteria were detected, mainly Staphylococcus aureus (70 strains, 33.3%); 95 strains (45.2%) of Gram-negative bacteria were detected, mainly Escherichia coli (20 strains, 9.5%), followed by Pseudomonas aeruginosa (17 strains, 8.1%); 8 strains (3.8%) of fungi were detected. (2) A total of 26 (28.3%) first-visit patients were positive for pathogenic microorganisms, and 172 (63.0%) re-visit patients were positive for pathogenic microorganisms. The rate of positive microorganism detection had significant differences between first-visit and re-visit patients ( P<0.05). (3) A total of 29 strains were detected in first-visit patients, including 16 strains (55.2%) of Gram-positive bacteria, 11 strains (37.9%) of Gram-negative bacteria and 2 strains (6.9%) of fungi. A total of 181 strains were detected in re-visit patients, including 91 strains (50.3%) of Gram-positive bacteria, 84 strains (46.4%) of Gram-negative bacteria and 6 strains (3.3%) of fungi. The microbial distribution was significantly different between first-visit and re-visit patients ( P<0.05). (4) Compared with first-visit patients, the resistance of Staphylococcus aureus isolated from the re-visit patients to spenicillin, oxacillin, ciprofloxacin, tetracycline, clindamycin, moxifloxacin, erythromycin, and levofloxacin were increased variably. No vancomycin-resistant Staphylococcus aureus was detected, indicating that the staphylococcus aureus presented in the wound was highly sensitive to vancomycin. Conclusions:Staphylococcus aureus is the most common microorganism in wound secretions in outpatients of wound healing center. The rate of positive pathogenic microorganisms in wound secretions of re-visit patients is significantly higher than that of first-visit patients, and the distribution of pathogenic microorganisms of first-visited and revisited patients differs significantly. The Staphylococcus aureus detected in re-visit patients has a higher resistance to common antibiotics compared with first-visit patients. It is suggested that timely detection of pathogenic microorganisms in outpatients and effective control and supervision of outpatient infections are important contents that cannot be ignored in the construction of wound healing center.