BACKGROUND:A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells,but the mechanism of its action is still unclear. OBJECTIVE:To summarize the research progress of mesenchymal stem cell secretome in recent years,to investigate the molecular mechanism of its therapeutic effect,to analyze the current problems and to look forward to the future development. METHODS:The terms"exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism"were used as English search terms in the PubMed database.Articles that were not related to the research purpose of the article and duplicated articles were excluded.At the same time,we combined the method of literature tracking.Finally,109 articles that met the criteria were incuded for the review. RESULTS AND CONCLUSION:(1)The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material,immunomodulatory factors,growth factors,etc.to target cells,by activating anti-apoptotic,regulating angiogenesis,modulating fibrosis and pro-survival pathways in target cells.(2)The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed.Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases.(3)Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years.However,due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components,the exact mechanism of its therapeutic effect is still unclear.(4)At present,further research is needed to identify the key targets of mesenchymal stem cell secretome,and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future.

Premature ovarian insufficiency(POI)is a complex endocrine disorder that significantly affects the physiological and repro-ductive functions of women,and it has become one of the main causes of infertility in women of childbearing age.The clinical features of POI include amenorrhea or oligomenorrhea,low estrogen or estrogen deficiency,and an increase in the level of gonadotropin.The in-cidence rate of POI tends to increase,yet its etiology and pathogenesis remain unclear.At present,the conventional treatment methods for POI have limited efficacy in fundamentally improving ovarian function or addressing the fertility issue.With the development of re-generative medicine,mesenchymal stem cells(MSCs)have become one of the research hotspots in POI therapy,and their exosomes have attracted wide attention as a promising"cell-free therapy".A number of animal experimental studies have shown that MSCs and their exosomes can exert a therapeutic effect on POI by affecting granulosa cell proliferation and apoptosis,promoting ovarian angiogen-esis,reducing oxidative stress and fibrosis,enhancing follicular development,and regulating immunity.In addition,related clinical studies have also made some progress.This article reviews the mechanisms and clinical effect of MSCs and their exosomes in the treatment of POI,in order to provide a reference for further research and bench-to-bedside translation of POI therapies.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder, with symptoms of menstrual disorders, hirsutisms, acne, and obesity. Studies have found that PCOS patients have a higher prevalence of anxiety, depression and sleep disorders than non-PCOS women, which may be related to the abnormal innervation. Meanwhile, it has been found that PCOS patients exhibit lower central level and higher peripheral levels of monoamine neurotransmitters (5-hydroxytryptamine, dopamine and norepinephrine). These imbalances can affect various clinical manifestations of PCOS, including the formation and development of metabolic and reproductive disorders, as well as anxiety and sleep disorders, through multiple pathways. This review summarizes recent research progress on the role of monoamine neurotransmitters in the physiological characteristics and clinical manifestations of PCOS patients, aiming to provide new insights into the neuroendocrine characteristics and pathogenesis of the syndrome.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder, with symptoms of menstrual disorders, hirsutisms, acne, and obesity. Studies have found that PCOS patients have a higher prevalence of anxiety, depression and sleep disorders than non-PCOS women, which may be related to the abnormal innervation. Meanwhile, it has been found that PCOS patients exhibit lower central level and higher peripheral levels of monoamine neurotransmitters (5-hydroxytryptamine, dopamine and norepinephrine). These imbalances can affect various clinical manifestations of PCOS, including the formation and development of metabolic and reproductive disorders, as well as anxiety and sleep disorders, through multiple pathways. This review summarizes recent research progress on the role of monoamine neurotransmitters in the physiological characteristics and clinical manifestations of PCOS patients, aiming to provide new insights into the neuroendocrine characteristics and pathogenesis of the syndrome.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

BACKGROUND:Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature.Currently,the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE:To review and summarize the latest research progress of laser therapy on chondrocytes,animal experiments and clinical efficacy,and to explore the possible mechanism of laser-mediated multi-pathway biological effects,so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS:A literature search was performed in CNKI,WanFang Data,VIP and PubMed databases for relevant literature published from 2018 to 2023,with"laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes"as the search terms in Chinese and English,respectively.Together with 14 articles searched manually,70 articles were finally included for review. RESULTS AND CONCLUSION:Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types:low-level laser therapy and high-level laser therapy.Differences in laser parameters and treatment protocols have a direct impact on laser efficacy.When appropriate parameters are used,low-level lasers show positive effects in cellular experiments,animal models,and clinical efficacy.High-level lasers have been less studied in the treatment of knee osteoarthritis,but some preliminary clinical studies have shown positive results.Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis,thereby reducing inflammatory response.Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors,promote cartilage matrix synthesis,inhibit matrix degradation,and effectively improve the repair process of cartilage tissue.Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis.In clinical trials,both low-and high-level laser can reduce patients'pain and improve functional activities.The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect.Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects.This provides direct evidence that laser promotes articular cartilage regeneration.

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.

Objective To cxplore the optimal levels of serum calcium,phosphorus and intact parathyroid hormone (iPTH) in peritoneal dialysis (PD) patients.Methods This study is a single center,retrospective cohort study.The associations between serum calcium,phosphorus and iPTH and all-cause mortality in 217 PD patients were analyzed.All patients started PD between January 1,2008 and April 30,2016 were enrolled and followed up to December 31,2016.At baseline and every 3 months,biochemical and therapeutic information was collected.Cox proportional hazard regression models and cubic splines analysis were employed to assess the lowest mortality risk ranges in serum markers of bone metabolism.Results There was no significantly difference between patients within target ranges based on KDOQI or KDIGO guideline and those outside the target ranges by Kaplan-Meier survival analysis.The lowest mortality risk ranges were 2.17-2.40 mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH by using Cox models and cubic splines analysis.Moreover,cumulate survival had significant difference between patients within the descriptive ranges and those out of the descriptive ranges at time-averaged values but not at baseline values.Conclusions The optimal time-averaged ranges of PD patients are 2.17-2.40mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH.These ranges need further validation by large population studies to further conform.