Asthenozoospermia is one of the important causes of male infertility， and its etiology is complex. Currently， there are no specific targeted therapeutic drugs available. Mitochondrial autophagy plays a crucial role in the progression of this disease. This article systematically summarizes the classification of mitochondrial autophagy and the mechanisms of mitochondrial autophagy mediated asthenozoospermia， and summarizes the research progress of traditional Chinese medicine monomers and formulas in intervening in asthenozoospermia. The results show that mitochondrial autophagy， as an important component of cellular quality control system， mainly includes two types： ubiquitin-dependent and non ubiquitin dependent. Among them， PTEN induced kinase 1/ Parkin signaling pathway mediated ubiquitin dependent mitochondrial autophagy is the most classic. This pathway can participate in regulating sperm physiological functions by degrading damaged mitochondria， maintaining mitochondrial functional homeostasis， antagonizing sperm mitochondrial damage caused by spermatogenesis-associated protein 33 abnormalities， and playing a key bidirectional regulatory role in the progression of asthenozoospermia. Traditional Chinese medicine monomers （allicin， eugenol， etc.） and compound formulas （Bushen qiangjing granules， Huangjing zanyu capsules， etc.） can target and activate or inhibit mitochondrial autophagy according to different pathological states， repair damaged mitochondrial function， improve sperm quality and vitality， fully reflecting the unique therapeutic characteristics of traditional Chinese medicine’s dual directional regulation and “balance‑oriented approach”.

Objective : To explore the effect and mechanism of total saponins of astragalus membranaceus combined with bone marrow mesenchymal stem cells (BMSCs) regulating the stromal cell-derived factor-1 (SDF-1) / chemo- kine receptor 4 ( CXCR4) pathway in the treatment of autoimmune premature ovarian failure ( POF) model rats． Methods : Rats were randomly divided into POF group，total saponins of astragalus membranaceus group，BMSCs group ，combination group ，combination + SDF-1 / CXCR4 pathway inhibitor ( AMD3100 ) group ，and control group，with 12 rats in each group．Except for the control group，all other groups of rats needed to construct a POF model．After successful modeling，treatment would begin．The drug injected into the tail vein once a week，and the drug injected into the abdominal cavity once a day for 4 weeks．ELISA was applied to detect the levels of anti ovari- an antibodies (AOAB) ，β-endorphin ( β-EP) ，vascular endothelial growth factor (VEGF) ，tumor necrosis factor- α (TNF-α) ，and interferon-γ ( INF-γ) in serum．Changes in ovarian index were detected．HE staining was ap- plied to detect the number of mature follicles，developing follicles，and blocked follicles in the ovary．Flow cytome- try was applied to detect the proportion of BMSCs in the ovaries．QRT-PCR was applied to detect the mRNA ex- pression of mesenchymal transition factor (cMET) ，hepatocyte growth factor (HGF) ，SDF-1，and CXCR4 in ovar- ian tissue．Western blot was applied to detect SDF-1 and CXCR4 proteins in ovarian tissue． Results : Compared with the control group，the serum levels of AOAB，TNF-α , INF-γ , and the number of blocked follicles in the ova- ries were higher，while the serum levels of β-EP，VEGF，ovarian index，the numbers of mature follicles and devel- oping follicles in the ovary，the expression of SDF-1，CXCR4 mRNA and protein were lower in the POF group (P < 0. 05) ．Compared with the POF group，the serum levels of AOAB，TNF-α , INF-γ , and the number of blocked follicles in the ovaries were lower，while the serum levels of β-EP，VEGF，ovarian index，the numbers of mature follicles and developing follicles in the ovary，the proportion of BMSCs，the expression of cMET ，HGF，SDF-1， CXCR4 mRNA and SDF-1，CXCR4 protein were higher in the total saponins of astragalus membranaceus group， BMSCs group，and combination group，and the corresponding indicators in the combination group showed the most obvious change trend (P＜0. 05) ．AMD3100 reversed the effect of total saponins of astragalus membranaceus com- bined with BMSCs on POF rats． Conclusion The combination of total saponins of astragalus membranaceus and BMSCs may inhibit inflammation in POF rats，promote follicular development，increase the proportion of BMSCs in the ovaries，and promote their homing by activating the SDF-1 / CXCR4 pathway，thereby improving ovarian func- tion．

Objective:To analyze the clinical characteristics of mannose phosphate isomerase-congenital disorders of glycosylation (MPI-CDG) and evaluated the outcomes following D-mannose treatment.Methods:This case-series study analyzed clinical manifestations, laboratory findings, imaging results, genetic data, and outcomes after D-mannose therapy in 5 children with MPI-CDG diagnosed at the Children′s Hospital of Fudan University between December 2014 and December 2024.Results:The age of onset ranged from 0.3 to 0.4 years in all 5 children, who initially presented with diarrhea and hypoglycemia. Associated manifestations included short stature (3 cases), anemia (3 cases), splenomegaly (3 cases), hepatomegaly (4 cases), elevated transaminases (4 cases), and hypoalbuminemia (4 cases). Liver pathology revealed hepatic fibrosis in 3 cases. Genetic testing identified 8 variants in the MPI gene, including 2 novel variants. Following D-mannose treatment, diarrhea and hypoglycemia resolved within 1-2 weeks in all children, with concurrent improvement in anemia. Notably except for Patient 1, who developed progressive splenomegaly, worsening hepatic fibrosis, and portal hypertension despite persistently normal transaminase and albumin levels, the other 4 children showed improvement in transaminase levels, resolution of hypoalbuminemia and amelioration of imaging abnormalities.Conclusions:MPI-CDG typically manifests in infancy with diarrhea and hypoglycemia, often accompanied by multi-system involvement. D-mannose treatment significantly improves metabolic abnormalities and most organ damages. However, close surveillance of liver status is warranted due to the risk of hepatic fibrosis progression in some cases.

ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index （DFI） and sperm mitochondrial membrane potential （MMP） in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group （64 cases） and a control group （64 cases）. The experimental group received Yishen Tongluo prescription， while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate， sperm progressive motility （PR）， total sperm motility （PR+NP）， sperm function （sperm tail hypotonic swelling rate， sperm acrosin activity）， sperm DFI， and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study， and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study， including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% （9/61）， higher than that in the control group at 6.67% （4/60）， though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group （P<0.05）. Compared with the results before treatment， sperm PR， PR + NP， sperm tail hypotonic swelling rate， sperm acrosin activity， sperm DFI， and sperm MMP were significantly improved in both groups after treatment （P<0.05）， with greater improvements in the experimental group （P<0.05）. However， there was no significant change in sperm concentration in either group after treatment. During the study， no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility， increase spouse pregnancy rate， enhance sperm function， and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.

Environmental pollutants generated by industrialization,characterized by microplastics,are increasingly impairing male fertility in the form of"environmental hidden toxins".Although the concept of environmental toxicity has been proposed for a long time,its practical application remains limited.Therefore,this study innovatively introduces and elaborates on the concept of"environmental hidden toxins",highlighting its pathogenic characteristics,including latency,turbidity,consumptive nature,concurrent nature,and transmutation.Environmental hidden toxin can be classified into five categories based on the properties:stagnation toxins,scorching toxins,turbid toxins,desiccating toxins,and latent toxins.The core pathogenesis of environmental hidden toxins-induced male infertility involves three stages:firstly,invading the lungs and spleen,leading to the gradual depletion of healthy qi;secondly,forming toxin-stasis complexes that obstruct the spermatic pathway;and lastly,penetrating deeply into the seminal chamber,directly damaging the genuine essence.The treatment principle emphasizes"strengthening the foundation and clearing the source,"advocating dual strategies of detoxification and strengthening vital qi.This includes enhancing clarity and lowering turbidity,fortifying the earth to generate metal to replenish healthy qi;resolving stasis,unblocking collaterals,and dispelling toxins to eliminate pathogenic factors;and nourishing the kidneys,replenishing essence,and expelling toxins to preserve the genuine essence.All the above approaches form a holistic traditional Chinese medicine(TCM)strategy that treating both manifestation and root cause of disease.The study provides theoretical foundations and offers novel clinical insights into TCM interventions for male infertility caused by environmental pollutants.

Objective:To analyze effects of T11TS in the treatment of Cryptococcus neoformans fungal infection and the regula-tion of T-cell calcineurin(CaN)-activated T lymphoid nuclear factor(NFAT)pathway.Methods:SD rats infected with Cryptococcus neoformans were treated with immunoenhancer T11TS.Flow cytometry,Western blot and nuclear translocation were used to detect the changes of T cell function and related signal pathway.Results:The number of Cryptococcus neoformans in lung and spleen of CT3 group was significantly less than Cryptococcus neoformans infection group,CT1 group and CT2 group(P<0.05).The results of flow cy-tometry showed that the expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 in Cryptococcus neoformans infection group were significantly lower than control group(P<0.05).The expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 of CT1,CT2 and CT3 groups were significantly higher than Cryptococcus neoformans infection group(P<0.05).The results of Western blot were similar to those of flow cytometry.Conclusion:T11TS in the treatment of Cryptococcus neoformans infection can enhance the immunity of the body by up-regulating the expression of related signal factors in the CaN-NFAT pathway of T lymphocytes,increasing the expression of NFAT and IL-2,stimulating the activation and proliferation of T lymphocytes.

Environmental pollutants generated by industrialization,characterized by microplastics,are increasingly impairing male fertility in the form of"environmental hidden toxins".Although the concept of environmental toxicity has been proposed for a long time,its practical application remains limited.Therefore,this study innovatively introduces and elaborates on the concept of"environmental hidden toxins",highlighting its pathogenic characteristics,including latency,turbidity,consumptive nature,concurrent nature,and transmutation.Environmental hidden toxin can be classified into five categories based on the properties:stagnation toxins,scorching toxins,turbid toxins,desiccating toxins,and latent toxins.The core pathogenesis of environmental hidden toxins-induced male infertility involves three stages:firstly,invading the lungs and spleen,leading to the gradual depletion of healthy qi;secondly,forming toxin-stasis complexes that obstruct the spermatic pathway;and lastly,penetrating deeply into the seminal chamber,directly damaging the genuine essence.The treatment principle emphasizes"strengthening the foundation and clearing the source,"advocating dual strategies of detoxification and strengthening vital qi.This includes enhancing clarity and lowering turbidity,fortifying the earth to generate metal to replenish healthy qi;resolving stasis,unblocking collaterals,and dispelling toxins to eliminate pathogenic factors;and nourishing the kidneys,replenishing essence,and expelling toxins to preserve the genuine essence.All the above approaches form a holistic traditional Chinese medicine(TCM)strategy that treating both manifestation and root cause of disease.The study provides theoretical foundations and offers novel clinical insights into TCM interventions for male infertility caused by environmental pollutants.

Objective:To analyze effects of T11TS in the treatment of Cryptococcus neoformans fungal infection and the regula-tion of T-cell calcineurin(CaN)-activated T lymphoid nuclear factor(NFAT)pathway.Methods:SD rats infected with Cryptococcus neoformans were treated with immunoenhancer T11TS.Flow cytometry,Western blot and nuclear translocation were used to detect the changes of T cell function and related signal pathway.Results:The number of Cryptococcus neoformans in lung and spleen of CT3 group was significantly less than Cryptococcus neoformans infection group,CT1 group and CT2 group(P<0.05).The results of flow cy-tometry showed that the expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 in Cryptococcus neoformans infection group were significantly lower than control group(P<0.05).The expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 of CT1,CT2 and CT3 groups were significantly higher than Cryptococcus neoformans infection group(P<0.05).The results of Western blot were similar to those of flow cytometry.Conclusion:T11TS in the treatment of Cryptococcus neoformans infection can enhance the immunity of the body by up-regulating the expression of related signal factors in the CaN-NFAT pathway of T lymphocytes,increasing the expression of NFAT and IL-2,stimulating the activation and proliferation of T lymphocytes.

Objective:To analyze the clinical characteristics of mannose phosphate isomerase-congenital disorders of glycosylation (MPI-CDG) and evaluated the outcomes following D-mannose treatment.Methods:This case-series study analyzed clinical manifestations, laboratory findings, imaging results, genetic data, and outcomes after D-mannose therapy in 5 children with MPI-CDG diagnosed at the Children′s Hospital of Fudan University between December 2014 and December 2024.Results:The age of onset ranged from 0.3 to 0.4 years in all 5 children, who initially presented with diarrhea and hypoglycemia. Associated manifestations included short stature (3 cases), anemia (3 cases), splenomegaly (3 cases), hepatomegaly (4 cases), elevated transaminases (4 cases), and hypoalbuminemia (4 cases). Liver pathology revealed hepatic fibrosis in 3 cases. Genetic testing identified 8 variants in the MPI gene, including 2 novel variants. Following D-mannose treatment, diarrhea and hypoglycemia resolved within 1-2 weeks in all children, with concurrent improvement in anemia. Notably except for Patient 1, who developed progressive splenomegaly, worsening hepatic fibrosis, and portal hypertension despite persistently normal transaminase and albumin levels, the other 4 children showed improvement in transaminase levels, resolution of hypoalbuminemia and amelioration of imaging abnormalities.Conclusions:MPI-CDG typically manifests in infancy with diarrhea and hypoglycemia, often accompanied by multi-system involvement. D-mannose treatment significantly improves metabolic abnormalities and most organ damages. However, close surveillance of liver status is warranted due to the risk of hepatic fibrosis progression in some cases.

ObjectiveTo observe the clinical efficacy of herb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription in the treatment of infertility induced by idiopathic asthenozoospermia （iAZS） with kidney-Yang deficiency and collateral obstruction syndrome and its effect on sperm DNA damage and superoxide dismutase （SOD） in the seminal plasma. MethodsA total of 112 eligible patients who met the inclusion criteria were randomly divided into an observation group （56 cases） and a control group （56 cases）. The patients in the observation group were treated with herb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription，while those in the control group received levocarnitine oral liquid. The primary observation indicators included spouse pregnancy rate，progressive motility （PR），and total sperm motility，and the secondary observation indicators included sperm DNA fragmentation index （DFI），SOD in the seminal plasma， and improvement of TCM syndromes. The treatment cycle was 12 weeks. Before and after treatment，the PR，total sperm motility，sperm DFI，SOD in the seminal plasma， and TCM syndrome scores were recorded. The patients were followed up for 12 weeks and the pregnancy status of spouses within 24 weeks （half a year） was recorded. The clinical efficacy of the two groups was evaluated. ResultThe pregnancy rate of spouses in the observation group was 15.69% （8/51）， higher than 3.85% （2/52） in the control group （χ²=4.118，P<0.05）. The total effective rate of the observation group was 88.24%（45/51）， superior to 69.23% （36/52）in the control group （Z=-3.402，P<0.01）. After treatment， PR， total sperm motility，sperm DFI， SOD in the seminal plasma， and TCM syndromes of the two groups were improved compared with those before treatment （P<0.05）， and the observation group was superior to the control group （P<0.05）. ConclusionHerb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription in the treatment of iAZS-induced infertility patients with kidney-Yang deficiency and collateral obstruction syndrome can increase PR，total sperm motility， and SOD level in the seminal plasma， reduce sperm DFI，improve the TCM symptoms of patients， and improve the pregnancy rate of spouses. The mechanism may be attributed to the fact that this treatment can increase the SOD level in the seminal plasma of patients，enhance the body's antioxidant function，protect sperm from oxidative stress damage，and reduce sperm DFI.