Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of 268275 pre-hospital CVD emergency cases were recorded in Yantai City, showing an increasing annual trend (AAPC=7.16%, P=0.002). Emergency volume, daily temperature, atmospheric pressure, and PM₁₀ displayed marked seasonal patterns, with summer bottoms and winter peaks for emergencies, daily temperature higher in summer and lower in winter, and the inverse for atmospheric pressure. Correlation analysis showed that both daily temperature and atmospheric pressure were positively correlated with O₃, with correlation coefficients of 0.745 and 0.723, respectively; negatively correlated with PM_2.5, with correlation coefficients of −0.246 and −0.235, respectively; and negatively correlated with PM₁₀, with correlation coefficients of −0.241 and −0.229, respectively (P < 0.05). A U-shaped correlation was revealed between daily temperature and pre-hospital CVD emergency risk. Using 24 °C as the reference, risk was elevated at both low and high daily temperatures, with the strongest cold effect at –11 ℃ (RR=1.53, 95%CI: 1.35, 1.73) and strongest heat effect at 30 ℃ (RR=1.06, 95%CI: 1.01, 1.11); cold effects were prolonged (lag0–14d) compared to heat effects. Atmospheric pressure exhibited a positive association with emergencies; using a median of 1012.2 hPa as the reference, the maximum risk occurred at 1037 hPa (RR=1.25, 95%CI: 1.03, 1.52), with a 0–5 d lag. In the subgroup analysis, the impact of low temperature was more pronounced among females (RR_{−9 ℃}=1.66), people over 60 years (RR_{−9 ℃}=1.91), and rural residents (RR_{−9 ℃}=1.76). High atmospheric pressure significantly increased the risk of pre-hospital CVD emergency among females (RR_{1035 hPa}=1.54), people under 18 years (RR_{1035 hPa}=3.62), and rural residents (RR_{1035 hPa}=1.46). The sensitivity analysis results indicated that, after excluding the impact of pandemic and the degrees of freedom for time variations, the effects of daily average temperature and atmospheric pressure on pre-hospital CVD emergency volume were consistent with the primary analysis findings. Conclusion Both non-optimal temperature and atmospheric pressure significantly increase the pre-hospital CVD emergency volume; therefore, emergency medical services should develop targeted response protocols, optimize resource allocation, and intensify public health education to mitigate the pre-hospital burden attributable to temperature and pressure fluctuations.

ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

ObjectiveTo explore the mechanism by which Qiangjing tablets （QJT） alleviate the spermatogenic function damage caused by varicocele （VC） based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway-mediated oxidative stress. MethodsTen Sprague-Dawley （SD） rats were randomly assigned into a control group and a model group. Pathological examination confirmed the stability of the model. Thirty-six SD rats were randomized into control， model， low-dose （0.23 g·kg^-1） QJT， medium-dose （0.46 g·kg^-1） QJT， high-dose （0.92 g·kg^-1） QJT， and mazhilin （61.7 mg·kg^-1） groups， with 6 rats in each group. A rat model of experimental left varicocele （ELV） was established by partially ligating the left renal vein to simulate the human nutcracker syndrome. The rats were administrated with corresponding agents once a day for 28 consecutive days. The in vitro testicular culture model of rats was established through the Transwell chamber method and intervened with QJT-containing sera （2.3， 4.6， and 9.2 g·kg^-1）. Microscopic observation was carried out for the morphology of the left kidney. A micrometer was used to measure the diameter of the left spermatic vein （LSV）. The body weights of rats were recorded weekly， and the epididymis and testis weights were measured. The pathological changes of the testicular tissue was observed via hematoxylin-eosin （HE） staining. The levels of testosterone （T） in the cell culture supernatant and reactive oxygen species （ROS） in the rat testicular tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Flow cytometry was employed to determine the ROS content. Immunohistochemical staining was conducted to analyze Keap1， Nrf2， 3β-hydroxysteroid dehydrogenase （3β-Hsd）， GATA-binding protein-4 （Gata-4）， and proto-oncogene receptor tyrosine kinase （C-kit）. The ultrastructure of the tissue was observed by transmission electron microscopy （TEM）. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining. The expression of Keap1， Nrf2， glutathione S-transferase α2 （Gsta2）， glutathione S-transferase μ1 （Gstm1）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （Nqo1）， and thioredoxin reductase 1 （Txnrd1） was quantified by Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. ResultsCompared with the control group， the ROS content and the percentage of apoptotic cells in the model group were significantly increased （P<0.01）， the T concentration was significantly decreased （P<0.01）， the mRNA and protein expressions of Keap1 were significantly increased （P<0.01）， and the mRNA and protein expressions of Nrf2， Gsta2， Gstm1， HO-1， Nqo1 and Txnrd1 were significantly decreased （P<0.05）. Compared with the model group， the ROS content and the percentage of apoptotic cells in each dose group of the Qiangjing Tablets were significantly reduced （P<0.05）， and the mRNA and protein expressions of Keap1 were significantly decreased （P<0.05）， while the mRNA and protein expressions of Nrf2， Gsta2， Gstm1， HO-1， Nqo1 and Txnrd1 were significantly increased （P<0.05）. ConclusionQJT improves sperm motility in the rat model of VC by modulating the Keap1/Nrf2 signaling pathway and reducing oxidative stress injury.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To analyze the characteristics of BRCA gene mutations in patients with ovarian epithelial carcinoma and fallopian tube carcinoma, and to investigate the impact of mutations in the functional domains of the BRCA genes on the prognosis of patients.Methods:This research collected a total of 273 patients diagnosed with primary ovarian epithelial carcinoma or fallopian tube carcinoma by pathological examination at the First Affiliated Hospital of Nanjing Medical University between January 2009 and December 2023.Data on their BRCA gene mutation status, clinicopathological data, and follow-up information were collected. A retrospective analysis was conducted to evaluate the association between BRCA gene mutations and patients' prognosis, including progression free survival (PFS) and overall survival (OS) time.Results:Among the 273 patients with ovarian or fallopian tube carcinoma, 101 cases (37.0%, 101/273) were positive for BRCA gene mutations (BRCA-positive group), while 172 cases (63.0%, 172/273) were negative for BRCA gene mutations (BRCA-negative group). (1) Clinicopathological characteristics: compared with the BRCA-negative group, the BRCA-positive group had a younger age at diagnosis, lower proportion of postmenopausal status, and lower recurrence rate (all P<0.05). Additionally, the BRCA-positive group showed a higher prevalence of family history of gynecological malignancies and a higher rate of no visible residual disease (R0) resection, all with statistical significance (all P<0.05). (2) Characteristics of BRCA gene mutations: among the 101 BRCA-positive patients, 74 cases (27.1%, 74/273) had BRCA1 gene mutations, 26 cases (9.5%, 26/273) had BRCA2 gene mutations, and 1 case (0.4%, 1/273) had indeterminate mutation records. According to the American College of Medical Genetics and Genomics (ACMG) 2015 guideline, mutations of uncertain significance accounted for 22.8% (23/101), likely pathogenic mutations accounted for 10.9% (11/101), and pathogenic mutations accounted for 59.4% (60/101), with 5.9% (6/101) unclassifiable. BRCA1 and BRCA2 genes have three (RING, DBD, BRCT) and two (RAD51-BD, DBD) major functional domains, respectively. Among the 89 BRCA-positive patients with detailed domain mutation data, the overall domain mutation rate was 40.4% (36/89), distributed as follows: DBD 14.6% (13/89), BRCT 12.4% (11/89), RING 4.5% (4/89), and RAD51-BD 9.0% (8/89). (3) Association between BRCA gene functional domain mutations and prognosis: among 77 patients with advanced stage (Ⅲ-Ⅳ) ovarian epithelial carcinoma in the BRCA-positive group with functional domain mutation data, the median PFS time was significantly longer in the 31 patients with domain mutations compared to the 46 patients with non-domain mutations (not reached during the follow-up period, vs 26.0 months; P=0.035). However, there was no significant difference in median OS time between the two groups (not reached during the follow-up period, vs 67.0 months; P=0.513). Median PFS time was longer in 13 patients with mutations in the DBD functional domain than that in 64 patients with mutations outside the DBD functional domain (not reached during the follow-up period, vs 28.0 months; P=0.042), whereas there was no significant difference in the comparison of median OS time between the two groups (not reached during the follow-up period, vs 67.0 months; P=0.321). (4) Association between BRCA gene functional domain mutations and efficacy of poly adenosine diphosphate ribose polymerase inhibitor (PARPi) maintenance therapy: among 51 advanced stage ovarian epithelial carcinoma patients who received PARPi maintenance therapy in the BRCA-positive group, 20 patients with domain mutations demonstrated significantly longer median PFS time compared to 31 patients with non-domain mutations (not reached during the follow-up period, vs 31.0 months; P=0.039). However, no significant difference was observed in median OS time between the two groups (not reached during the follow-up period, vs 53.0 months; P=0.178). PARPi maintenance therapy was more effective in the 9 patients with mutations in the DBD functional domain than that in the 42 patients with mutations located outside the DBD structural domain, with significant differences observed in both median PFS time (both not reached during the follow-up period; P=0.007) and median OS time (both not reached during the follow-up period; P=0.037). In contrast, patients with mutations in the BRCT or RAD51-BD domains showed no significant differences in either median PFS or OS time compared to patients with mutations outside these domains (all P>0.05). Conclusions:Patients with ovarian epithelial carcinoma and fallopian tube carcinoma who harbor BRCA functional domain mutations exhibit significantly longer median PFS time compared to those with non-domain mutations. Moreover, among patients received PARPi maintenance therapy, those with mutations in the DBD domain have a better median PFS and OS time benefit.

As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective:To analyze the characteristics of BRCA gene mutations in patients with ovarian epithelial carcinoma and fallopian tube carcinoma, and to investigate the impact of mutations in the functional domains of the BRCA genes on the prognosis of patients.Methods:This research collected a total of 273 patients diagnosed with primary ovarian epithelial carcinoma or fallopian tube carcinoma by pathological examination at the First Affiliated Hospital of Nanjing Medical University between January 2009 and December 2023.Data on their BRCA gene mutation status, clinicopathological data, and follow-up information were collected. A retrospective analysis was conducted to evaluate the association between BRCA gene mutations and patients' prognosis, including progression free survival (PFS) and overall survival (OS) time.Results:Among the 273 patients with ovarian or fallopian tube carcinoma, 101 cases (37.0%, 101/273) were positive for BRCA gene mutations (BRCA-positive group), while 172 cases (63.0%, 172/273) were negative for BRCA gene mutations (BRCA-negative group). (1) Clinicopathological characteristics: compared with the BRCA-negative group, the BRCA-positive group had a younger age at diagnosis, lower proportion of postmenopausal status, and lower recurrence rate (all P<0.05). Additionally, the BRCA-positive group showed a higher prevalence of family history of gynecological malignancies and a higher rate of no visible residual disease (R0) resection, all with statistical significance (all P<0.05). (2) Characteristics of BRCA gene mutations: among the 101 BRCA-positive patients, 74 cases (27.1%, 74/273) had BRCA1 gene mutations, 26 cases (9.5%, 26/273) had BRCA2 gene mutations, and 1 case (0.4%, 1/273) had indeterminate mutation records. According to the American College of Medical Genetics and Genomics (ACMG) 2015 guideline, mutations of uncertain significance accounted for 22.8% (23/101), likely pathogenic mutations accounted for 10.9% (11/101), and pathogenic mutations accounted for 59.4% (60/101), with 5.9% (6/101) unclassifiable. BRCA1 and BRCA2 genes have three (RING, DBD, BRCT) and two (RAD51-BD, DBD) major functional domains, respectively. Among the 89 BRCA-positive patients with detailed domain mutation data, the overall domain mutation rate was 40.4% (36/89), distributed as follows: DBD 14.6% (13/89), BRCT 12.4% (11/89), RING 4.5% (4/89), and RAD51-BD 9.0% (8/89). (3) Association between BRCA gene functional domain mutations and prognosis: among 77 patients with advanced stage (Ⅲ-Ⅳ) ovarian epithelial carcinoma in the BRCA-positive group with functional domain mutation data, the median PFS time was significantly longer in the 31 patients with domain mutations compared to the 46 patients with non-domain mutations (not reached during the follow-up period, vs 26.0 months; P=0.035). However, there was no significant difference in median OS time between the two groups (not reached during the follow-up period, vs 67.0 months; P=0.513). Median PFS time was longer in 13 patients with mutations in the DBD functional domain than that in 64 patients with mutations outside the DBD functional domain (not reached during the follow-up period, vs 28.0 months; P=0.042), whereas there was no significant difference in the comparison of median OS time between the two groups (not reached during the follow-up period, vs 67.0 months; P=0.321). (4) Association between BRCA gene functional domain mutations and efficacy of poly adenosine diphosphate ribose polymerase inhibitor (PARPi) maintenance therapy: among 51 advanced stage ovarian epithelial carcinoma patients who received PARPi maintenance therapy in the BRCA-positive group, 20 patients with domain mutations demonstrated significantly longer median PFS time compared to 31 patients with non-domain mutations (not reached during the follow-up period, vs 31.0 months; P=0.039). However, no significant difference was observed in median OS time between the two groups (not reached during the follow-up period, vs 53.0 months; P=0.178). PARPi maintenance therapy was more effective in the 9 patients with mutations in the DBD functional domain than that in the 42 patients with mutations located outside the DBD structural domain, with significant differences observed in both median PFS time (both not reached during the follow-up period; P=0.007) and median OS time (both not reached during the follow-up period; P=0.037). In contrast, patients with mutations in the BRCT or RAD51-BD domains showed no significant differences in either median PFS or OS time compared to patients with mutations outside these domains (all P>0.05). Conclusions:Patients with ovarian epithelial carcinoma and fallopian tube carcinoma who harbor BRCA functional domain mutations exhibit significantly longer median PFS time compared to those with non-domain mutations. Moreover, among patients received PARPi maintenance therapy, those with mutations in the DBD domain have a better median PFS and OS time benefit.