Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

Objective:To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS).Methods:A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children′s Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test.Results:A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis ( χ2=5.022, P=0.025), distant metastasis ( χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group ( χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion:Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Objective:To develop the children′s postoperative health-related quality of life scale for thyroid cancer and to test its reliability and validity.Methods:The first draft of the scale was developed through literature search, focus group meetings, and a pre-survey, and 116 children (76 for testing and 40 for external validation) with thyroid cancer attending Beijing Children′s Hospital of Capital Medical University were selected to answer the scale, to screen and categorize the questions and to form the final scale with multiple dimensions.Results:The children′s postoperative health-related quality of life scale for thyroid cancer contained 5 dimensions and 29 questions. Exploratory factor analysis showed that the cumulative variance explained by the 5 factors was 64.343%. Confirmatory factor analysis showed correlations between the questions and dimensions of this scale, fair convergent validity for the scale, and good discriminant validity. The validity of the validity scale showed that there was a existing correlation between the questions and the validity scale of this scale. The item-dimension correlation coefficients showed that the questions in each dimension were well differentiated. The total Cronbach′s α coefficient of the scale was 0.930, the folded half reliability was 0.843, and retest reliabilities at 2 weeks, 1 month, and 3 months after the initial test were respectively 0.936, 0.922, and 0.910.Conclusion:The developed children′s postoperative health-related quality of life scale for thyroid cancer has good reliability and validity and can be used to assess the health-related quality of life of children after thyroid cancer surgery.

Ketosis in dairy cows is often accompanied by apoptotic and inflammatory responses in adipose tissue.In order to investigate the effect of pro-apoptotic protein Bid on adipocyte apoptosis in cows with ketosis,the adipose tissue was stained by TUNEL staining technique in this study to observe the apoptotic changes in adipose tissue of cows with ketosis.In the in vivo test,protein ex-pression of apoptosis-related factors Bid,Bax,C-Caspase-3,Bcl-2 and inflammation marker factors C1q,IL-1β,IL-10 and IL-6 in adipose tissues of healthy cows and ketosis cows were detected by Western blot.In the in vitro assay,the adipocyte lipolysis model was constructed by culturing pri-mary bovine adipocytes in vitro to inhibit Bid and adding isoproterenol(ISO),and the protein ex-pression levels of apoptosis-related molecules and inflammation-related molecules in adipocytes were detected by Western blot technique.The results of TUNEL staining showed that the protein expression of pro-apoptotic factors Bid,Bax and C-Caspase-3,and pro-inflammatory markers TNF-a,IL-1β,and IL-6 were significantly higher,and the protein expression of complement C1q,anti-ap-optotic factor Bcl-2,and anti-inflammatory factor IL-10 were significantly lower in adipose tissues of ketosis cows compared with that of healthy cows.The in vitro results showed that the protein expression levels of apoptosis and inflammation-related factors in adipocytes treated with the ISO group were significantly higher compared with those in the control group,while the protein ex-pression levels of apoptosis and inflammation-related factors in adipocytes treated with the addi-tion of the Bid inhibitor group were significantly lower.The above results showed that inhibition of Bid could alleviate the apoptotic and inflammatory responses of ISO on adipocytes.This will fur-ther clarify the role of Bid/C1q in the regulation of adipose tissue and cell apoptosis and inflamma-tion in ketosis cows.

Purpose::Autologous osteoperiosteal transplantation (AOPT) is one of the most feasible and effective techniques for cystic osteochondral lesions of the talus (OLT). However, few reports have been reported about the process of graft-host bone healing and bone articular surface reconstruction, which help us to further understand the actual situation of bone healing and modify surgical methods.Methods::The case series study retrospectively evaluated 33 osteochondral lesions in 30 patients undertaking AOPT for OLT with subchondral cysts from December 2016 to October 2021. According to CT observation, we used 4 variables to describe the bony articular repair, including the integration of the articular surface, the height of the bone filling, the status of bone union, and the appearance of bone resorption or cystic change. We also analyzed the demographic data and clinical function. Descriptive statistics were used for demographic and clinical variables. Normally distributed data were presented as mean ± SD, and non-normally distributed data were presented as median (Q 1, Q 3). Associations between these variables and the primary clinical outcomes were examined using t-test or one-way ANOVA test for continuous variables. Results::The patients’ mean age was (41.7 ± 14.0) years old and the mean follow-up time was (29.6 ± 17.8) months. The chondral lesion size was (14.3 ± 4.1) mm. The cyst depth was (10.9 ± 3.7) mm. Significant improvements were observed in functional outcomes (according to the numeric rating scale for pain when walking and the American orthopedic foot and ankle society score) between the preoperative and latest follow-up evaluations, from 4.2 ± 2.1 to 2.2 ± 2.0 ( p < 0.001), and from 66.8 ± 12.9 to 83.2 ± 10.4, respectively ( p < 0.001). The overall satisfaction reached 8.3 of 10 points. All patients returned to sports and their median daily steps reached 8000 steps with 27 (81.8%) patients walking over 6000 steps daily. According to CT observation, "discontinuous bony articular surface and gap > 1 mm" was found in 27 grafts (81.8%), and "below the level of the adjacent articular surface, ≤1 mm" in a third of the grafts. Abnormal height of bone filling affected numeric rating scale score ( p=0.049) and American Orthopedic Foot and Ankle Society score ( p =0.027). Of note, bone resorption or cystic changes appeared in up to 13 autografts (39.4%). Conclusions::AOPT is an effective and acceptable technique for cystic OLT. Bone reconstruction is essential for large cystic OLT. How to get better bony articular reconstruction and avoid cyst recurrence should still be paid more attention.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.
Humans ; Mice ; Animals ; Female ; Silybin/therapeutic use* ; Caco-2 Cells ; Polymers/chemistry* ; Nanoparticles/chemistry* ; Cell Line, Tumor ; Breast Neoplasms/pathology* ; Tumor Microenvironment

ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.

Aim To investigate the effects of angelica sinensis polysaccharide (ASP) antagonizing 5-fluorou-raeil (5-FU) on spleen stress erythropoiesis in mice and its related mechanism. Methods C57BL/6J mice aged 6-8 weeks were randomly divided into control group, ASP group, 5-FU group and ASP + 5-FU group. The mouse body weight during the modeling pe-riod was recorded, and peripheral blood routine and the number of mononuclear cells in the bone marrow of femur were measured. Histopathology of spleen was de-tected, also the index and cellularity of spleen were analyzed. BFU-E of spleen mononuclear cells was counted. The number of F4/80

Rhythm control is crucial part of comprehensive management of atrial fibrillation (AF). Rhythm control can reduce the burden of AF effectively, reduce symptoms, and improve the prognosis in early AF. Antiarrhythmic drugs (AADs) are the first-line treatment for rhythm-control strategies. This consensus focuses on the principle of rhythm control in AF, the characteristics of AADs, and the medication recommendations for patients in different populations suffering from AF. Hence, this consensus aims to support clinical decision-making for AF therapy.
Humans ; Anti-Arrhythmia Agents/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Consensus ; China