Diagnostic and therapeutic approaches for non-obstructive azoospermia (NOA) remain limited in current clinical practice, urgently requiring new assistive technologies to advance diagnosis and treatment. As a crucial medium for intercellular communication, exosomes show broad potential in the treatment and diagnosis of NOA. This review summarizes research progress on exosomes from multiple sources. Firstly, mesenchymal stem cell-derived exosomes (e.g., from bone marrow, urine, umbilical cord, adipose tissue) promote spermatogenesis recovery by enhancing spermatogenic cell proliferation, regulating relevant gene expression, supplying growth factors, and providing antioxidant stress protection. Secondly, cell-derived exosomes exert effects by modulating the spermatogonial stem cell microenvironment (e.g., upregulating GFRα1 expression) and directly communicating with germ cells. Thirdly, amniotic fluid-derived exosomes increase spermatogenic cell numbers and upregulate expression of spermatogenesis-related genes such as DAZL and VASA. Furthermore, molecules carried by exosomes—such as miRNAs (e.g., miR-31-5p, miR-26a-5p) and transfer RNA-derived fragments—hold potential diagnostic value in distinguishing non-obstructive from obstructive azoospermia and predicting micro-TESE success rates. This paper aims to provide theoretical basis and research directions for the clinical application of exosomes in NOA.

OBJECTIVE: To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). METHODS: Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center II of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (> 32.00%), measuring 2.33% ± 0.58% and 0.80% ± 0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (> 4.00%), with the values of 3.36% ± 0.35% and 2.93% ± 1.36%. Both probands were found to harbor homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls. CONCLUSION The homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.
Humans ; Male ; Asthenozoospermia/genetics* ; Adult ; Sperm Injections, Intracytoplasmic ; Pedigree ; Spermatozoa ; Female ; Exome Sequencing

Objective:To construct a risk prediction model of hyperuricemia (HUA) for community-dwelling residents.Methods:This cross-sectional study was conducted from March to November 2020. A total of 1 967 residents in the Nanzhai community of Taiyuan city were selected by stratified sampling method as study subjects, among whom 1 555 (80%) subjects served as the training set and the remaining 412 (20%) as the validation set. Blood uric acid was measured in all subjects and level>420 mmol/L was defined as HUA. The risk factors of HUA were determined with multivariate logistic regression analysis, and a risk prediction model was constructed. The Hosmer-Lemeshow goodness-of-fit test and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model.Results:Among the 1 555 residents in the training set, HUA was detected in 285 cases (18.3%). The detection rate in men was significantly higher than that in women [29.8% (220/739) vs. 8.0% (65/816), χ 2=123.17, P<0.05]. Compared to non-HUA group, the waist circumference and BMI, and the proportion of smoking, drinking, staying up late, and prevalence of hypertension and dyslipidemia were significant higher in HUA group. There was significant difference in the frequency of drinking tea, coffee, milk, and eating fruits, as well as the amount of beverages consumed between the two groups ( P<0.05). Multivariate logistic regression analysis showed that high BMI ( OR=1.132, 95 %CI:1.070-1.197, P<0.001), coffee consumption ( OR=1.337, 95 %CI:1.027-1.742, P=0.032), and dyslipidemia ( OR=1.479, 95 %CI:1.049-2.086, P=0.025) were risk factors of HUA, while female sex ( OR=0.213, 95 %CI:0.146-0.390, P<0.001) was protective factor of HUA. When all factors were included in the logistic regression model, gender, BMI, coffee consumption, beverage intake, sodium salt intake, sleep quality, and dyslipidemia ( OR=0.213, 1.113, 1.353, 0.788, 1.320, 0.788, 1.651) were important components of the HUA prediction model. By substituting the constant, these factors, and the regression coefficients into the logistic regression equation, the Logit(P) formula was obtained: Logit(P)=-1.530-1.547×gender+0.107×BMI+0.303×coffee consumption frequency-0.238×sodium salt intake+0.278×beverage intake-0.238×sleep quality+0.502×dyslipidemia. The ROC curve showed an area under the curve ( AUC) of 0.750. The Hosmer-Lemeshow goodness-of-fit test: P=0.632, indicating a satisfactory fit. When the formula was applied to the validation set for internal validation, the AUC was 0.745. Conclusion:The occurrence of HUA is influenced by multiple factors. The prediction model constructed in this study has good prediction performance,which may be used to predict the risk of HUA in primary care settings for community-dwelling residents.

Objective:To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). Methods:Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center Ⅱ of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).Results:Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (>32.00%), measuring 2.33%±0.58% and 0.80%±0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (>4.00%), with the values of 3.36%±0.35% and 2.93%±1.36%. Both probands were found to harbor homozygous c. 2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls.Conclusion:The homozygous c. 2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.

OBJECTIVE To explore the mechanism of Yishen Qingli Huoxue Formula(YQHF)improving renal fibrosis by inhib-iting HIF1-α using data mining,molecular docking,and in vivo and in vitro experiments.METHODS The expression changes of HIF1-α in renal biopsy tissues of patients with chronic kidney disease(CKD)in the GEO database were analyzed.Molecular docking was used to clarify the interaction mode between YQHF effective monomers and HIF1-α.Thirty SD rats were randomized to sham,model,low-dose YQHF,high-dose YQHF,and losartan potassium groups(n=6 per group).Unilateral ureteral obstruction(UUO)was used to induce renal fibrosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured,and kidney sections were stained with HE and Masson to assess pathology and fibrosis.Renal HIF1-α protein expression was quantified by Western blot.A renal fibro-sis cell model was established by inducing NRK-52E cells with TGF-β1,and the cells were divided into control,model,YQHF,HIF1-α inhibitor,HIF1-α inhibitor+YQHF,HIF1-α agonist,and HIF1-α agonist+YQHF groups.Western blot analysis was used to detect the protein expression levels of HIF1-α,COL-1,and α-SMA,and to observe the mechanism of YQHF-containing serum in protecting renal tubular epithelial cells.RESULTS Data mining showed HIF1-α expression in the CKD group was significantly higher than in the control group(P<0.01).Molecular docking indicated YQHF core components had good binding affinity to HIF1-α.In vivo,com-pared with the sham group,HE staining revealed tubular atrophy and inflammatory-cell infiltration,and Masson staining showed in-creased collagen deposition in UUO model rats(P<0.01).Serum creatinine and blood urea nitrogen were also elevated in the model group(P<0.05),together with up-regulated renal expression of COL-1,α-SMA and HIF-1α(P<0.01).After intervention with either high-dose or low-dose YQHF or losartan potassium,these pathological changes were attenuated:collagen deposition decreased(P<0.01),creatinine and BUN fell to varying degrees(P<0.05),and renal COL-1,α-SMA and HIF-1α levels were down-regulated(P<0.01);immunohistochemistry confirmed reduced HIF-1α in UUO kidneys(P<0.01).In NRK-52E cells,TGF-β1 stimulation mark-edly increased COL-1,α-SMA and HIF-1α protein levels(P<0.01).Both YQHF and chloramphenicol alone down-regulated these proteins(P<0.05,P<0.01),and their combination produced stronger inhibition of HIF-1α than YQHF alone(P<0.05).Conversely,the HIF-1α agonist fenbendazole-d3 reversed YQHF's anti-fibrotic effect,re-elevating COL-1,α-SMA and HIF-1α(P<0.01),with no significant difference versus agonist alone.CONCLUSION YQHF may inhibit extracellular matrix deposition and delay renal fi-brosis progression by suppressing HIF1-α accumulation,providing new theoretical evidence for traditional Chinese medicine in treat-ing renal fibrosis.

OBJECTIVE To explore the mechanism of Yishen Qingli Huoxue Formula(YQHF)improving renal fibrosis by inhib-iting HIF1-α using data mining,molecular docking,and in vivo and in vitro experiments.METHODS The expression changes of HIF1-α in renal biopsy tissues of patients with chronic kidney disease(CKD)in the GEO database were analyzed.Molecular docking was used to clarify the interaction mode between YQHF effective monomers and HIF1-α.Thirty SD rats were randomized to sham,model,low-dose YQHF,high-dose YQHF,and losartan potassium groups(n=6 per group).Unilateral ureteral obstruction(UUO)was used to induce renal fibrosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured,and kidney sections were stained with HE and Masson to assess pathology and fibrosis.Renal HIF1-α protein expression was quantified by Western blot.A renal fibro-sis cell model was established by inducing NRK-52E cells with TGF-β1,and the cells were divided into control,model,YQHF,HIF1-α inhibitor,HIF1-α inhibitor+YQHF,HIF1-α agonist,and HIF1-α agonist+YQHF groups.Western blot analysis was used to detect the protein expression levels of HIF1-α,COL-1,and α-SMA,and to observe the mechanism of YQHF-containing serum in protecting renal tubular epithelial cells.RESULTS Data mining showed HIF1-α expression in the CKD group was significantly higher than in the control group(P<0.01).Molecular docking indicated YQHF core components had good binding affinity to HIF1-α.In vivo,com-pared with the sham group,HE staining revealed tubular atrophy and inflammatory-cell infiltration,and Masson staining showed in-creased collagen deposition in UUO model rats(P<0.01).Serum creatinine and blood urea nitrogen were also elevated in the model group(P<0.05),together with up-regulated renal expression of COL-1,α-SMA and HIF-1α(P<0.01).After intervention with either high-dose or low-dose YQHF or losartan potassium,these pathological changes were attenuated:collagen deposition decreased(P<0.01),creatinine and BUN fell to varying degrees(P<0.05),and renal COL-1,α-SMA and HIF-1α levels were down-regulated(P<0.01);immunohistochemistry confirmed reduced HIF-1α in UUO kidneys(P<0.01).In NRK-52E cells,TGF-β1 stimulation mark-edly increased COL-1,α-SMA and HIF-1α protein levels(P<0.01).Both YQHF and chloramphenicol alone down-regulated these proteins(P<0.05,P<0.01),and their combination produced stronger inhibition of HIF-1α than YQHF alone(P<0.05).Conversely,the HIF-1α agonist fenbendazole-d3 reversed YQHF's anti-fibrotic effect,re-elevating COL-1,α-SMA and HIF-1α(P<0.01),with no significant difference versus agonist alone.CONCLUSION YQHF may inhibit extracellular matrix deposition and delay renal fi-brosis progression by suppressing HIF1-α accumulation,providing new theoretical evidence for traditional Chinese medicine in treat-ing renal fibrosis.

Objective:To construct a risk prediction model of hyperuricemia (HUA) for community-dwelling residents.Methods:This cross-sectional study was conducted from March to November 2020. A total of 1 967 residents in the Nanzhai community of Taiyuan city were selected by stratified sampling method as study subjects, among whom 1 555 (80%) subjects served as the training set and the remaining 412 (20%) as the validation set. Blood uric acid was measured in all subjects and level>420 mmol/L was defined as HUA. The risk factors of HUA were determined with multivariate logistic regression analysis, and a risk prediction model was constructed. The Hosmer-Lemeshow goodness-of-fit test and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model.Results:Among the 1 555 residents in the training set, HUA was detected in 285 cases (18.3%). The detection rate in men was significantly higher than that in women [29.8% (220/739) vs. 8.0% (65/816), χ 2=123.17, P<0.05]. Compared to non-HUA group, the waist circumference and BMI, and the proportion of smoking, drinking, staying up late, and prevalence of hypertension and dyslipidemia were significant higher in HUA group. There was significant difference in the frequency of drinking tea, coffee, milk, and eating fruits, as well as the amount of beverages consumed between the two groups ( P<0.05). Multivariate logistic regression analysis showed that high BMI ( OR=1.132, 95 %CI:1.070-1.197, P<0.001), coffee consumption ( OR=1.337, 95 %CI:1.027-1.742, P=0.032), and dyslipidemia ( OR=1.479, 95 %CI:1.049-2.086, P=0.025) were risk factors of HUA, while female sex ( OR=0.213, 95 %CI:0.146-0.390, P<0.001) was protective factor of HUA. When all factors were included in the logistic regression model, gender, BMI, coffee consumption, beverage intake, sodium salt intake, sleep quality, and dyslipidemia ( OR=0.213, 1.113, 1.353, 0.788, 1.320, 0.788, 1.651) were important components of the HUA prediction model. By substituting the constant, these factors, and the regression coefficients into the logistic regression equation, the Logit(P) formula was obtained: Logit(P)=-1.530-1.547×gender+0.107×BMI+0.303×coffee consumption frequency-0.238×sodium salt intake+0.278×beverage intake-0.238×sleep quality+0.502×dyslipidemia. The ROC curve showed an area under the curve ( AUC) of 0.750. The Hosmer-Lemeshow goodness-of-fit test: P=0.632, indicating a satisfactory fit. When the formula was applied to the validation set for internal validation, the AUC was 0.745. Conclusion:The occurrence of HUA is influenced by multiple factors. The prediction model constructed in this study has good prediction performance,which may be used to predict the risk of HUA in primary care settings for community-dwelling residents.

Objective:To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). Methods:Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center Ⅱ of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).Results:Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (>32.00%), measuring 2.33%±0.58% and 0.80%±0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (>4.00%), with the values of 3.36%±0.35% and 2.93%±1.36%. Both probands were found to harbor homozygous c. 2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls.Conclusion:The homozygous c. 2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.

With the increasing prevalence of obesity and diabetes mellitus, the incidence rate of metabolic dysfunction-associated steatotic liver disease (MASLD) is on the rise. MASLD has become the most common chronic liver disease, affecting more than 30% of the global population and causing serious social and economic burden. Numerous studies have shown that the development of MASLD is associated with an increased risk of heart and blood vessel disease (CVD). In 2010, the American Heart Association proposed the concept of ideal cardiovascular health (ICH); in 2022, the scoring criteria were updated with the introduction of the Life′s Essential 8 (LE8), comprising 4 ideal cardiovascular behaviors (optimal diet, exercise, no smoking, mean sleep 7-9 h/d) and 4 ideal cardiovascular conditions (blood pressure<120/80 mmHg (1 mmHg=0.133 kPa) with no medication, no history of diabetes mellitus and fasting blood glucose<5.6 mmol/L or HbA1c<5.7%, non-high density lipoprotein cholesterol<3.36 mmol/L, body mass index<25 kg/m 2). It aims to provide clear, actionable goals for CVD prevention by providing a direct, simple way to quantify health behaviors. A growing number of studies also confirm that the higher level of LE8 metrics is closely associated with the lower risk of MASLD. This article reviews the latest research progress on ICH metrics for reducing risk of MASLD, in order to provide references for early and effective prevention and comprehensive management of MASLD patients.

OBJECTIVE To explore the potential mechanism of Yishenqinglihuoxue Formula(YSQLF)in treating chronic kidney disease fibrosis in rats based on UHPLC-Q-TOF-MS technology and network pharmacology.METHODS UHPLC-Q-TOF-MS was used for qualitative analysis of Yishenqinglihuoxue Formula-containing serum.Targets of the plasma constituents and the disease were retrieved from SwissTargetPrediction,OMIM,GeneCards,and other databases.Then the protein-protein interaction(PPI)network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment.Cytoscape software was em-ployed to construct the"drug-compound-core target-pathway"network and the targets and signaling pathways of Yishenqinglihuoxue Formula against fibrosis were predicted.A model of renal fibrosis was established to verify the core targets and pathway proteins.RE-SULTS A total of 56 constituents migrating to blood of Yishenqinglihuoxue Formula were identified.97 common targets of the constit-uents and the disease and 33 core targets were screened out.KEGG enrichment and PPI network analysis showed that Yishenqingli-huoxue Formula may play a role in the treatment of fibrosis through PI3K/Akt and other pathways.Furthermore,the results of animal experiments showed that Yishenqinglihuoxue Formula could reduce the levels of Scr and BUN,improve fibrosis areas,inhibit the acti-vation of the PI3K/Akt pathway,and reduce the protein expression of TNF-α.CONCLUSION Yishenqinglihuoxue Formula may play a role in the treatment of fibrosis by inhibiting PI3K/Akt signaling pathway and inhibiting TNF-α expression.