The immune microenvironment plays a pivotal role in maintaining ovarian homeostasis. Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder, is closely associated with immune microenvironment imbalance. This review systematically describes the dysregulation of innate immune cells (e.g., macrophages, natural killer cells and dendritic cells) and adaptive immune cells (e.g., Th1, Th2, Treg and Th17) in PCOS, highlighting their impacts on ovarian function, insulin resistance, and hyperandrogenemia. These findings underscore the central role of immune microenvironment disturbances in PCOS pathogenesis. Additionally, the association between gut microbiota dysbiosis and PCOS is explored, emphasizing how gut microbiota influences metabolic byproducts and hormonal levels to contribute to PCOS development. Furthermore, therapeutic strategies targeting immune microenvironment imbalance such as modulating macrophage polarization, restoring Th1/Th2 and Th17/Treg balance, and ameliorating gut microbiota dysbiosis are discussed, offering novel insights for PCOS immunotherapy. In conclusion, this review comprehensively analyzes the pathogenesis of PCOS from the perspective of the immune microenvironment, aiming to provide a theoretical foundation and reference for future research and clinical practice.

OBJECTIVE To explore the changes of serum Toll-like receptor(TLR)2,TLR4 and 25 hydroxyvitamin D[25(OH)D]in the general anesthesia orthopedic surgery patients with postoperative pulmonary infections and analyze the distribution and drug resistance of pathogens.METHODS A total of 59 general anesthesia orthopedic surgery patients with postoperative pulmonary infections who were treated in Tianjin Fifth Central Hospital from Jul.2019 to Jul.2024 were chosen as the infection group,meanwhile,65 patients who underwent the same surger-y but did not have postoperative pulmonary infection or other acute and chronic infections were chosen as the non-infection group.The etiological characteristics of the postoperative pulmonary infections and the drug re-sistance rates were analyzed.The clinical data and the levels of serum TLR2,TLR4 and 25(OH)D were observed and compared between the two groups of patients.The values of the above indicators in diagnosis of the postopera-tive pulmonary infections in the general anesthesia orthopedic surgery were analyzed.RESULTS Totally 63 strains of pathogens were isolated from the 59 general anesthesia orthopedic surgery patients with postoperative pulmona-ry infections,36(57.14％)of which were gram-negative bacteria.3 of 15 Pseudomonas aeruginosa strains were resistant to meropenem;4 of 12 Klebsiella pneumoniae strians were resistant to meropenem;all of the 11 Staph-ylococcus aureus strains were methicilin-resistant S.aureus.The proportions of patients with age,hypoproteine-mia and diabetes mellitus,the serum TLR2 and TLR4 levels were higher in the infection group than in the non-infection group(P＜0.05),while the 25(OH)D level of the infection group was lower than that of the no in-fection group(P＜0.05).The area under the curves(AUCs)of serum TLR2,TLR4,25(OH)D and the joint de-tection of the above indicators were respectively 0.817,0.801,0.787 and 0.917 in diagnosis of postoperative pul-monary infections in the general anesthesia orthopedic surgery patients,and the AUC of the joint detection of the indicators was greater than that of the single detection(P＜0.05).CONCLUSIONS The general anesthesia or-thopedic surgery patients with postoperative pulmonary infections show high expressions of serum TLR2 and TLR4 and the low expression of 25(OH)D.The joint detection of the above indexes has higher diagnostic value.The gram-negative bacteria are dominant among the pathogens causing the infections.The pathogens vary in the drug resistance.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

The immune microenvironment plays a pivotal role in maintaining ovarian homeostasis. Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder, is closely associated with immune microenvironment imbalance. This review systematically describes the dysregulation of innate immune cells (e.g., macrophages, natural killer cells and dendritic cells) and adaptive immune cells (e.g., Th1, Th2, Treg and Th17) in PCOS, highlighting their impacts on ovarian function, insulin resistance, and hyperandrogenemia. These findings underscore the central role of immune microenvironment disturbances in PCOS pathogenesis. Additionally, the association between gut microbiota dysbiosis and PCOS is explored, emphasizing how gut microbiota influences metabolic byproducts and hormonal levels to contribute to PCOS development. Furthermore, therapeutic strategies targeting immune microenvironment imbalance such as modulating macrophage polarization, restoring Th1/Th2 and Th17/Treg balance, and ameliorating gut microbiota dysbiosis are discussed, offering novel insights for PCOS immunotherapy. In conclusion, this review comprehensively analyzes the pathogenesis of PCOS from the perspective of the immune microenvironment, aiming to provide a theoretical foundation and reference for future research and clinical practice.

OBJECTIVE To explore the changes of serum Toll-like receptor(TLR)2,TLR4 and 25 hydroxyvitamin D[25(OH)D]in the general anesthesia orthopedic surgery patients with postoperative pulmonary infections and analyze the distribution and drug resistance of pathogens.METHODS A total of 59 general anesthesia orthopedic surgery patients with postoperative pulmonary infections who were treated in Tianjin Fifth Central Hospital from Jul.2019 to Jul.2024 were chosen as the infection group,meanwhile,65 patients who underwent the same surger-y but did not have postoperative pulmonary infection or other acute and chronic infections were chosen as the non-infection group.The etiological characteristics of the postoperative pulmonary infections and the drug re-sistance rates were analyzed.The clinical data and the levels of serum TLR2,TLR4 and 25(OH)D were observed and compared between the two groups of patients.The values of the above indicators in diagnosis of the postopera-tive pulmonary infections in the general anesthesia orthopedic surgery were analyzed.RESULTS Totally 63 strains of pathogens were isolated from the 59 general anesthesia orthopedic surgery patients with postoperative pulmona-ry infections,36(57.14％)of which were gram-negative bacteria.3 of 15 Pseudomonas aeruginosa strains were resistant to meropenem;4 of 12 Klebsiella pneumoniae strians were resistant to meropenem;all of the 11 Staph-ylococcus aureus strains were methicilin-resistant S.aureus.The proportions of patients with age,hypoproteine-mia and diabetes mellitus,the serum TLR2 and TLR4 levels were higher in the infection group than in the non-infection group(P＜0.05),while the 25(OH)D level of the infection group was lower than that of the no in-fection group(P＜0.05).The area under the curves(AUCs)of serum TLR2,TLR4,25(OH)D and the joint de-tection of the above indicators were respectively 0.817,0.801,0.787 and 0.917 in diagnosis of postoperative pul-monary infections in the general anesthesia orthopedic surgery patients,and the AUC of the joint detection of the indicators was greater than that of the single detection(P＜0.05).CONCLUSIONS The general anesthesia or-thopedic surgery patients with postoperative pulmonary infections show high expressions of serum TLR2 and TLR4 and the low expression of 25(OH)D.The joint detection of the above indexes has higher diagnostic value.The gram-negative bacteria are dominant among the pathogens causing the infections.The pathogens vary in the drug resistance.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

Glaucoma is one of the most common optic neuropathies, featuring progressive retinal ganglion cell damage and visual field loss (Tham et al., 2014; Xu et al., 2020). Currently, the only effective treatment for this condition is the reduction of intraocular pressure (IOP) (Palmberg, 2001; Heijl et al., 2002). Canaloplasty is a proven bleb-independent surgery with good efficacy and safety profiles in primary open-angle glaucoma (POAG) (Gołaszewska et al., 2021). However, early transient postoperative IOP elevation has been reported in up to 30% of cases (Riva et al., 2019), similar to that commonly observed in other internal drainage glaucoma surgeries such as implantation using iStent (0%-21.0%), CyPass (10.8%), and Hydrus (4.8%-6.5%) (Lavia et al., 2017). This complication may be a predictor of poor reserve in the outflow system and is potentially associated with surgical failure. Nonetheless, the exact pathophysiology of glaucoma remains unknown, and studies clarifying the risk factors for postoperative IOP elevation have been scarce.
Humans ; Intraocular Pressure ; Glaucoma, Open-Angle/surgery* ; Incidence ; Treatment Outcome ; Risk Factors

Diabetes mellitus （DM） is a metabolic disease mainly characterized by chronic hyperglycemia and has multiple etiologies. The complications of DM， such as coronary atherosclerosis， nephropathy， foot disease and cardiac dysfunction， have high morbidity， disability rate and mortality. DM and its complications have a long course of disease and are easy to relapse， which are difficult to be cured， seriously affecting people's life and health. NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is an important component of inflammatory response and innate immune system. The inflammatory cascade induced by NLRP3 activation is involved in the occurrence and development of DM as well as its complications by releasing inflammatory factors， damaging endothelial cells and affecting metabolic stress. Therefore， as the core of the inflammatory response， NLRP3 may provide a new target for the treatment of DM and its complications. Traditional Chinese medicine plays a key role in the treatment of DM and its complications， and has a regulatory effect on NLRP3. Thus it has become a novel research strategy to prevent and treat DM and its complications via modulating NLRP3. However， at present， there are relatively scattered reports and a lack of systematic review on the role of traditional Chinese medicine in the treatment of DM and its complications from the perspective of NLRP3. As a result， this paper reviewed domestic and foreign literature in recent years and conducted the discussion from two aspects： the influence of NLRP3 on the occurrence and development of DM and its complications， and the progress of traditional Chinese medicine in intervening in DM and its complications through NLRP3. This paper provided reference for the research on the regulation of NLRP3 and a new direction for the treatment of DM and its complications.

Objective To observe the formation of the biofilm in endotracheal tubes,the characteristics of etiology,drug resistance and effect on the biofilm and ventilator-associated pneumonia (VAP) of inhaled N-acetylcysteine (NAC).Method We selected 117 tracheally intubated and undergoing mechanical ventilation for ≥48 h in our hospital ICU from September 2010 to August 2012.All the cases were randomly divided into control group (60 cases) and study group (57 cases).The patients in the study group were treated with different doses of aerosolized NAC according to different ages,starting the first administration within 12 hours of mechanical ventilation,once every 8 hours,until stopping mechanical ventilation.Comparison was performed on the two groups in biofilm structure under the scanning electron microscopy,biofilm culture positive rate,VAP incidence,the etiology and drug resistance of the lower airway secretions and biofilms.Result (1) Electron microscopy showed that biofilm had formed in the endotracheal tube inner wall in early period of mechanical ventilation.With prolonged mechanical ventilation,biofilm structure improved.At the same time of mechanical ventilation,the thickness of biofilm in the study group decreased as compared with the control group.(2) Biofilm culture positive rate and incidence of ventilator-associated pneumonia decreased in the study group compared with in the control group (65％(37/57) vs.80％(48/60),P＜0.05;11％ (6/57)vs.32％(19/60),P＜0.01).(3) Alarge number of pathogenic bacteria colonized in the biofilm and gram-negative bacilli dominated.With prolonged mechanicalventilation,theculturedpathogensconvergedfromthelowerairwaysecretionsandbiofilm.Conclusion With prolonged mechanical ventilation,biofilm structure was improved.Inhalation of NAC can inhibit biofilm formation and reduce the incidence of VAP.