ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology， molecular docking， and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards， Online Mendelian Inheritance in Man （OMIM）， PharmGKB， Therapeutic Target Database （TTD）， Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0， the STRING database was used to analyze the protein-protein interactions， and Cytoscape was used for the core target analysis and visualization. Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG） were employed for enrichment analysis. Molecular docking was carried out in Autodock， and cell experiments were conducted to verify the prediction results. In the cell experiments， estradiol and progesterone （E₂+P） were used to intervene in human mammary epithelial/MCF-10A cells， and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 （CCK-8） was used to measure the cell proliferation， and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot， respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained， from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes， which may be related to protein kinase B （Akt）-related molecular functions， estrogen signaling pathway， prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 （ESR1）， serine/threonine kinase 1 （Akt1）， non-receptor tyrosine kinase （SRC）， and signal transducer and activator of transcription 3 （STAT3） all had strong binding activity with the nine active ingredients， suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway and the Janus kinase （JAK）/STAT3 signaling pathway. The results of cell experiments showed that E₂+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells （P<0.05）， while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E₂+P （P<0.05）. Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E₂+P （P<0.01）. The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K， Akt， JAK2， and STAT3 in MCF-10A cells treated with E₂+P （P<0.01）. The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K， p-Akt/Akt， p-JAK2/JAK2， and p-STAT3/STAT3 in MCF-10A cells treated with E₂+P （P<0.05）. ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells， which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.

OBJECTIVE To investigate the mechanism of Bushen huoxue formula in improving pregnancy outcomes in mice with antiphospholipid antibody-related recurrent spontaneous abortion （aPL-RSA）. METHODS SPF female BALB/c mice were randomly divided into normal control group， adjuvant control group， model group， and Bushen huoxue formula group. The aPL-RSA mouse model was established by immunization with β 2 glycoproteinⅠcombined with Freund’s adjuvant. From gestational day 0， the Bushen huoxue formula group was administered 1.653 6 g/（kg·d） of the prescription by gavage， while the other three groups received an equal volume of normal saline， twice daily for 15 consecutive days. The uterine appearance of pregnant mice was observed； individual embryo weight was recorded， and the embryo resorption rate was calculated. The proportion of activated CD41 + CD62p + platelets in platelet-rich plasma （PRP） was detected. Serum levels of thromboxane B2 （TXB2） and platelet factor 4 （PF4） were measured. Morphological changes of placental tissue were observed. The cell apoptosis rate of placental tissue was detected. The levels of malondialdehyde （MDA） content， tot al superoxide dismutase （T-SOD） activity， the interleukin-1β （IL-1β） and IL-18， the protein expressions of matrix metalloproteinase-3 （MMP-3）， MMP-9， nuclear proliferation antigen-67 （Ki67）， superoxide dismutase 2 （SOD2）， Nod-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and caspase-1， as well as the mRNA expressions of superoxide dismutase 2（SOD2）， NLRP3， ASC and caspase-1 of placental tissue were detected. RESULTS Compared with the normal control group and adjuvant control group， the model group showed significant decreases in individual embryo weight， T-SOD activity of placental tissue， and relative expression levels of SOD2 mRNA and protein （ P ＜0.05）； while significant increases were observed in embryo resorption rate， proportion of activated CD41 + CD62p + platelets in PRP， serum levels of TXB2 and PF4， placental cell apoptosis rate， MDA content in placental tissue， relative protein expressions of MMP-3， MMP-9 and Ki67， relative protein and mRNA expression levels of NLRP3， ASC and caspase-1 as well as IL-1β and IL-18 levels （ P ＜0.05）. The model group also exhibited irregular uterine morphology with localized atrophy in some uterine horns； placental tissue showed fragmentation of decidual cells， extensive vacuolization and necrosis of trophoblast cells in the labyrinthine zone， accompanied by vascular reduction. After intervention with Bushen huoxue formula， the above indicators were significantly reversed （ P ＜0.05）， and uterine morphology and pathological damage were markedly improved. CONCLUSIONS Bushen huoxue formula can effectively improve pregnancy outcomes in aPL-RSA model mice， and its mechanism may be closely related to inhibiting platelet activation， reducing oxidative stress injury， enhancing trophoblast cell function， and suppressing the inflammatory response mediated by the NLRP3 inflammasome pathway.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Objective To observe the impact of brain-computer interface(BCI)robot combined with task-oriented training(TOT)on hand function and activities of daily living in stroke patients.Methods A total of 40 patients with subacute stroke who were hospitalized in the Department of Rehabilitation Medicine of Anhui No.2 Province People's Hospital from December 2022 to December 2024 were prospectively and consecutively included in this study.The stroke patients were randomly assigned to the experimental group and the control group using the random number table method,with 20 cases in each group.Baseline data were collected from all patients,including gender,age,personal history(smoking,drinking),past medical history(hypertension,diabetes),stroke type(hemorrhagic stroke,ischemic stroke),hemiplegia side(left,right),disease course,stroke location(basal ganglia,internal capsule),and admission assessment indicators(including kinesthetic and visual imagery questionnaire[KVIQ-20]score,mini-mental state examination[MMSE]score and National Institutes of Health stroke scale[NIHSS]score).Both groups of patients received conventional rehabilitation training and TOT.The experimental group then underwent BCI robot training combined with TOT on this basis.Both groups received treatments for 4 weeks,and the upper limb and hand functions of all patients were evaluated using the Fugl-Meyer upper extremity function assessment scale(FMA-UE),the wrist-hand part of the FMA-UE scale(FMA-WH),the Wolf motor function test(WMFT),and the modified Ashworth scale(MAS)before and after the treatment;the hand function related part(feeding[10 score],bathing[5 score],dressing[10 score],grooming[5 score],and toilet using[10 score])of modified Barthel index(MBI)was used to assess the patients'hand dexterity to perform daily activities.Results(1)No statistically significant differences were found in the baseline data between the two groups of patients(all P＞0.05).(2)Before treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(18.75±7.38),(2.95±1.54),(26.90±8.69),(1.10±0.66),and(15.45±1.82)respectively,while those in the control group were(15.90±5.39),(2.25±1.12),(24.15±6.78),(1.25±0.60),and(15.65±3.12)respectively.There were no statistically significant differences in the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI between the two groups before treatment(all P＞0.05).After 4 weeks of treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(27.10±7.76),(5.75±2.97),(40.85±10.19),(0.73±0.57),and(21.15±2.66)respectively,while those in the control group were(21.25±5.29),(4.00±1.49),(31.85±7.60),(0.73±0.64),and(17.40±3.14)respectively.The time main effects(Ftime values were 925.061,138.138,624.635 and 405.986 respectively,all P＜0.01),group main effects(Fgroup values were 4.460,4.562,5.011 and 4.411 respectively,all P＜0.05),and the interaction effects of time and group(Ftime×group values were 44.358,7.356,52.506 and 114.128 respectively,all P＜0.05)of FMA-UE,FMA-WH,WMFT and hand function related score of MBI scores were all significant.The time main effect of MAS scores was significant(Ftime value was 59.478,P＜0.01),while the group main effect(Fgroup value was 0.162,P＞0.05),the interaction effects of time and group(Ftime×group value was 1.652,P＞0.05)were not significant.Conclusion The combined task-oriented training with BCI robots can improve the upper limb and hand functions of stroke patients,enhance their ability to perform daily activities,and the effect is superior to that of single task-oriented training.

Objective To investigate the clinical efficacy of Chinese medicine sequential therapy combined with Clomiphene in the treatment of ovulatory disorder infertility(ODI),and to observe the effects of the combined therapy on the endometrial thickness,ovarian diameter,ovulation rate and pregnancy rate of the patients.Methods A total of 120 patients with ODI admitted to the Department of Obstetrics and Gynecology of the 7th People's Hospital of Zhengzhou from July 2021 to August 2023 were randomly divided into the control group and the observation group,with 60 patients in each group.The two groups were treated with Clomiphene,and additionally the observation group was treated with Chinese medicine sequential therapy of"nourishing yin and enriching blood,warming kidney to resolve phlegm and unblock collaterals,and tonifying kidney and strengthening spleen"in accordance with the menstrual cycle.Three menstrual cycles constituted a course of treatment.Before and after treatment,the changes in the traditional Chinese medicine(TCM)syndrome scores of the two groups were observed.After treatment for three menstrual cycles,the clinical efficacy,endometrial thickness,follicle diameter,ovulation rate,pregnancy rate,incidence of biphasic basal body temperature(BBT),and the incidence of adverse reactions after in the two groups were compared.Results(1)After three menstrual cycles of treatment,the total effective rate of the observation group was 96.67％(58/60)and that of the control group was 83.33％(50/60),and the comparison between the two groups showed that the efficacy of the observation group was significantly superior to that of the control group,the difference being statistically significant(x2=5.926,P＜0.05).(2)After three menstrual cycles of treatment,the TCM scores of patients in both groups were decreased significantly compared with those before treatment(P＜0.01),and the decrease of the scores in the observation group was significantly superior to that in the control group,with statistically significant differences(P＜0.01).(3)After three menstrual cycles of treatment,the follicle diameter of the observation group was longer than that of the control group,and the incidence of biphasic BBT[60.00％(36/60)],ovulation rate[63.33％(38/60)],and pregnancy rate[25.00％(15/60)]were higher than those of the control group,which were 31.67％(19/60),41.67％(25/60),and 10.00％(6/60),respectively.The differences of the above four indicators between the two groups were statistically significant(P＜0.05 or P＜0.01).However,the differences of endometrial thickness and the incidence of adverse reactions between the two groups were not statistically significant(P＞0.05).Conclusion Chinese medicine sequential therapy combined with Clomiphene exerts certain efficacy in treating patients with ODI,which can effectively relieve clinical symptoms,improve the BBT conditions,enhance the ovulation rate and pregnancy rate,with high safety.

Objective To investigate the temporal and spatial relationship between autophagosome formation during spermatid deformation and lipid droplet distribution in seminiferous tubules,thereby providing insights into the en-ergy sources underlying spermiogenesis.Methods Healthy adult wild-type male mice were used in this study.The expression profile of the autophagy marker microtubule-associated protein light chain 3(LC3)in the testis was ex-amined using immunohistochemical staining and Western blot.The ultrastructural features of autophagosomes were observed via transmission electron microscopy.Lipid droplets in the seminiferous tubules were visualized by Oil Red O staining,and the relationship between lipid metabolism and energy dynamics was assessed by measuring ATP content and ATPase activity.Results Autophagosomes were detected in deforming spermatids and Sertoli cells.LC3 was predominantly expressed in the cytoplasm of elongating spermatids,with increasing levels found from stages Ⅱ to Ⅳ.Concurrently,lipid droplets within these cells also increased,peaking in spermatids and residual bodies during stagesⅦ-Ⅷ,followed by a decline.In contrast,lipid droplets in Sertoli cells remained markedly in-creased during stages Ⅸ-Ⅰ and low during stages Ⅱ-Ⅷ.The change of ATP levels in the seminiferous tubules showed a similar pattern as Sertoli cell lipid content,whereas ATPase activity showed an inverse trend.All these changes displayed a clear stage-dependent manner.Conclusions During spermatid elongation in mice LC3 expres-sion,autophagosome formation,lipid droplet accumulation in both spermatozoa and Sertoli cells,as well as ATP and ATPase levels in seminiferous tubules exhibit a tightly coordinated spatiotemporal relationship.These findings suggest that autophagy and lipid metabolism synergistically contribute to the energy supply required for the extensive cellular remodeling that occurs during spermiogenesis.

Objective To explore the CT diagnosis and differential diagnosis of perivascular epithelioid cell neoplasms (PEComa), improve the accuracy of PEComa diagnosis, and reduce misdiagnosis. Methods CT findings of 8 cases of PEComa confirmed by pathology in Jining First People’s Hospital from January 2020 to April 2024 were retrospectively analyzed for the location, shape, size, boundary, plain scan density, and enhancement characteristics of the lesions. Results All 8 tumors were solitary, with 5 located in the kidney, 1 in the liver, 1 in the extraperitoneal space, and 1 in the retroperitoneal space. The tumors were round in 3 cases, oval in 1 case, and irregular in 4 cases. Seven cases were benign with clear boundaries and 1 case was malignant with unclear boundaries. On plain CT, 2 cases showed slightly low density, 3 cases showed slightly high density, and 3 cases showed low density. One tumor had uniform density, and 7 tumors had nonuniform density with internal necrosis and cystic changes. Contrast-enhanced CT revealed diverse enhancement patterns. Four cases showed a “fast in and fast out” enhancement pattern, with significant arterial-phase enhancement and reduced portal venous-phase enhancement. Three cases showed a “fast-in and slow-out” enhancement pattern, with significant enhancement in the arterial phase, persistent enhancement in the portal venous phase, and slightly reduced density in the delayed phase. One case showed mild enhancement in the arterial phase and significant enhancement in the portal venous phase. In 3 cases, multiple tortuous and thickened blood vessels were observed around the tumors, while 3 cases showed tortuous vascular shadows within the tumors. Conclusion PEComa demonstrates characteristic CT features, predominantly with “fast in and fast out” or “fast in and slow out” enhancement patterns. When thickened and tortuous blood vessels are observed within or around the tumor, PEComa should be considered in combination with clinical findings.

Chinese materia medica mainly prevents and treats diminished ovarian reserve by regulating PI3K/Akt, PI3K/Akt/mTOR, PI3K/Akt/FoxO3, PTEN/PI3K/Akt, TGF-β1/Smads, Nrf2/HO-1, AMPK and other signaling pathways. It also involves Hippo, Wnt / β-catenin, Notch and other signaling pathways, which can improve the ovarian environment, promote ovarian function repair, inhibit ovarian granulosa cell apoptosis, promote oocyte growth, regulate hormone levels, and play anti-inflammatory, anti-oxidation and anti-fibrosis roles.

Objective:To investigate the structural changes in the spinal cord in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and their relationship with clinical disability.Methods:This study was cross-sectional. A retrospective analysis of clinical and imaging data from 124 patients with MS (MS group), 101 patients with aquaporin-4 antibody-positive NMOSD (NMOSD group), and 110 healthy controls (HC group) from seven medical centers were conducted from January 2018 to October 2021. All subjects underwent 3D T 1WI, and the upper cervical spinal cord cross-sectional area (MUCCA) was segmented and measured. All patients completed the expanded disability status scale (EDSS) assessments at baseline and during follow-up, as well as the baseline 25-foot walk test (T25FW) and the nine-hole peg test (NHPT). Patients were classified into EDSS progression and non-progression groups based on follow-up EDSS scores. Comparisons of MUCCA among the three groups were conducted using analysis of covariance, controlling for age and sex as covariates. Pairwise comparisons between groups were performed using the HSD test. Univariate linear regression and logistic models were employed to identify candidate predictors of baseline clinical disability status or EDSS progression in the MS and NMOSD groups. L1 regularized multivariable linear regression analysis was used to determine independent predictors of baseline clinical disability status or EDSS progression. Independent predictors were then combined to establish a logistic regression model, and the model′s performance in predicting EDSS progression was evaluated using receiver operating characteristic analysis and the area under the curve (AUC). Results:A total of 144 patients completed follow-up EDSS assessments, with a follow-up duration of 3.30 (1.10, 6.42) years, including 82 patients in the MS group and 62 patients in the NMOSD group. Controlling for sex and age as covariates, the overall difference in MUCCA among the MS, NMOSD, and HC groups was statistically significant ( P=0.001). The MUCCA in the MS group was lower than that in the HC group, with a significant difference ( t=-2.54, P=0.007); the MUCCA in the NMOSD group was also lower than that in the HC group, with a significant difference ( t=-2.80, P=0.002). However, the difference in MUCCA between the MS and NMOSD groups was not statistically significant ( t=-0.40, P=0.882). In the MS group, MUCCA was an independent predictor of baseline EDSS score (β=-0.03), baseline T25FW score (β=-0.09), and baseline NHPT score (β=-0.30). In the NMOSD group, MUCCA (β=-0.08), age (β=0.06), and baseline EDSS score (β=-0.43) were independent predictors of EDSS progression, and the logistic regression model incorporating these three factors predicted EDSS progression with an AUC of 0.82. Conclusions:Significant spinal cord atrophy occurs in patients with both MS and NMOSD. Atrophy of the upper cervical spinal cord can predict the degree of disability in MS patients and the progression of clinical disability in NMOSD patients.