Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

Objective To optimize the oxygen therapy regimens for infants with pulmonary diseases during bronchoscopy.Methods A prospective randomized,controlled,and single-center clinical trial was conducted on 42 infants who underwent electronic bronchoscopy from July 2019 to July 2021.These infants were divided into a nasal cannula(NC)group and a modified T-piece resuscitator(TPR)group using a random number table.The lowest intraoperative blood oxygen saturation was recorded as the primary outcome,and intraoperative heart rate and respiratory results were recorded as the secondary outcomes.Results Compared with the NC group,the modified TPR group had a significantly higher level of minimum oxygen saturation during surgery and a significantly lower incidence rate of hypoxemia(P<0.05).In the modified TPR group,there were 6 infants with mild hypoxemia,2 with moderate hypoxemia,and 1 with severe hypoxemia,while in the NC group,there were 3 infants with mild hypoxemia,5 with moderate hypoxemia,and 9 with severe hypoxemia(P<0.05).The modified TPR group had a significantly lower incidence rate of intraoperative respiratory rhythm abnormalities than the NC group(P<0.05),but there was no significant difference in the incidence rate of arrhythmias between the two groups(P>0.05).Conclusions Modified TPR can significantly reduce the risk of hypoxemia in infants with pulmonary diseases during electronic bronchoscopy,and TPR significantly decreases the severity of hypoxemia and the incidence of respiratory rhythm abnormalities compared with traditional NC.

Objective:To compare hamstring tendon graft (HTG), ligament advanced reinforcement system (LARS), and mixed HTG & LARS ligament in reconstruction of posterior cruciate ligament (PCL).Methods:A retrospective study was conducted to analyze the 59 patients with PCL rupture who had been admitted to Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University for arthroscopic PCL reconstruction between January 2018 and August 2021. The patients were divided into 3 groups: in the HTG group of 21 cases [14 males and 7 females aged (37.8±12.6) years], PCL was reconstructed by HTG; in the LARS group of 20 cases [12 males and 8 females aged (34.3±9.1) years], PCL was reconstructed by LARS; in the mixed group of 18 cases [13 males and 5 females aged (33.2±8.3) years], PCL was reconstructed by the mixed HTG & LARS ligament. The 3 groups were compared in terms of Lysholm knee score, International Knee Documentation Committee (IKDC) score, and laxity disparity between bilateral knees at 1 and 2 years after surgery.Results:There was no statistically significant difference in the preoperative general data between the 3 groups, indicating comparability ( P>0.05). One year after surgery, the mixed group had a significantly higher IKDC score [(90.0±6.5) points] than the HTG group [(78.1±5.7) points] and the LARS group [(84.1±7.3) points], and a significantly higher Lysholm score [(88.9±5.5) points] and a significantly smaller laxity disparity between bilateral knees [(2.8±1.7) mm] than the HTG group [(81.8±4.6) points, (4.7±2.4) mm] ( P<0.05). Two years after surgery, the mixed group had a Lysholm score of (93.0±4.5) points, a IKDC score of (92.5±5.7) points, and a laxity disparity between bilateral knees of (2.3±1.8) mm, all significantly better than those in the HTG group [(88.5±5.5) points, (82.7±5.7) points, and (4.2±2.5) mm] and in the LARS group [(89.0±5.2) points, (86.5±7.3) points, and (3.8±2.2) mm] ( P<0.05). In all the 3 groups, the knee function scores and laxity disparities between bilateral knees at 1 and 2 years after surgery were significantly improved compared with the preoperative values ( P<0.05). Conclusions:Satisfactory clinical outcomes can be obtained after arthroscopic PCL reconstruction using HTG, LARS or the mixed HTG & LARS ligament. However, the mixed ligament as a graft can achieve better clinical efficacy than the other two grafts.

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.
Humans ; Male ; Azoospermia/pathology* ; East Asian People ; Exome Sequencing ; Mutation ; Proteins/genetics*

Analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacology were employed to identify the potential quality markers(Q-markers) of Gei Herba. According to the new concept of Q-markers in traditional Chinese medicine(TCM), the AHP-EWM was applied to quantitatively identify the Q-markers of Gei Herba. The AHP was used for the weight analysis of primary indicators(factor layer), and the EWM for the analysis of literature and experimental data of secondary indicators(control layer). In addition, network pharmacology was employed to build the "component-target-disease-efficacy" network for Gei Herba, and the components showing strong associations with the Qi-replenishing, spleen-invigorating, blood-tonifying, Yin-nourishing, lung-moistening, and phlegm-resolving effects of Gei Herba were screened out. According to the results of AHP-EWM and network pharmacology, four components, i.e., ellagic acid, gallic acid, gemin G, and gemin C, were finally identified as potential Q-markers of Gei Herba. In this study, the AHP-EWM and network pharmacology were employed to screen the Q-markers of Gei Herba, which provided ideas for the quantitative evaluation and identification of Q-markers of TCM.
Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Analytic Hierarchy Process ; Entropy ; Medicine, Chinese Traditional

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.
Female ; Male ; Humans ; Laser Therapy ; Lower Extremity ; Ultrasonography ; Femoral Artery ; Ultrasonography, Interventional

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To explore the early clinical efficacy of primary total hip arthroplasty(THA) with Corail standard stems (KS type) and high offset stems (KHO type), by analyzing the postoperative radiographic parameters of different offset of femoral components with Corail stem which has a neck-shaft angle of 135 ° in unilateral primary THA, by comparing the measurement results on both sides and analyzing the reconstruction of the postoperative femoral offset and the hip joint function recovery. METHODS: A retrospective analysis was made of 186 patients with unilateral hip joint lesions who underwent the first total hip arthroplasty with Johnson & Johnson Corail prostheses from January 2015 to June 2017. According to the use of femoral prostheses with different eccentricities during the operation, the patients were divided into high eccentricity group and standard eccentricity group. In the high eccentricity group, there were 52 cases of Corail high eccentricity prosthesis(KHO type), including 20 females and 32 males;aged 21 to 71 years old with an average of(50.6±13.2) years;body mass index(BMI) was (26.0±4.1) kg/m². The standard eccentricity group included 134 Corail standard femoral stem prostheses(KS type), 57 females and 77 males;aged 18 to 77 years old with an average of (47.3±14.0) years;BMI was (25.3±3.5) kg/m². The abduction arm, femoral eccentricity, acetabular eccentricity and the length difference of lower limbs were measured on the postoperatively positive X-ray film of the hip joint. Harris score and related complications were recorded before and after the operation, and the stability of the prosthesis was analyzed. RESULTS: There were significant differences in femoral eccentricity, joint eccentricity and abduction arm between the affected side and the healthy side in the high eccentricity group(P<0.05). There were significant differences in femoral eccentricity and acetabular eccentricity between the affected side and the healthy side in the standard eccentricity group(P<0.05). There were significant differences in combined eccentricity, abduction arm and length of lower limbs between two groups(P<0.05). In the high eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and joint eccentricity(r=0.633, P<0.001;r=0.384, P=0.005;r=0.690, P<0.001). The same results were also obtained in the healthy side(r=0.688, P<0.001;r=0.574, P<0.001;r=0.765, P<0.001). In the standard eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and combined eccentricity(r=0.734, P<0.001;r=0.418, P<0.001;r=0.749, P<0.001). The same results were also obtained in the healthy side(r=0.775, P<0.001;r=0.397, P<0.001;r=0.773, P<0.001). The difference of the length of both lower limbs was significantly correlated with the difference of bilateral joint eccentricity and bilateral abduction arm (r=0.376, P=0.006;r=-0.346, P=0.012). There was no significant correlation between the difference of the length of both lower limbs and the difference of bilateral joint eccentricity and bilateral abduction arm (r=-0.009, P=0.919;r=-0.036, P=0.682). There was no significant difference in Harris score between two groups at the last follow-up(P>0.05). At the last follow-up, Trendelenburg was negative in all patients in both groups, and the prostheses were stable. CONCLUSION Both Corail standard stem and high offset stem may be effectively reconstruct the femoral offset, reconstruct the anatomical structure and biomechanics of the hip joint, and maintain the length of lower limbs and the stability of the hip joint in the unilateral primary total hip arthroplasty. Although the offset of the femur was not reconstructed normally in some cases, the stability of the components and postoperative function were not affected.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Adolescent ; Arthroplasty, Replacement, Hip/methods* ; Retrospective Studies ; Hip Prosthesis ; Femur/surgery* ; Lower Extremity

OBJECTIVE: To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder. METHODS: Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder. RESULTS: Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder. CONCLUSIONS Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.
Animals ; Bile/metabolism* ; Biomarkers/metabolism* ; Body Weight ; Cattle ; Diet, High-Fat ; Female ; Lipid Metabolism ; Lipid Metabolism Disorders/metabolism* ; Lipids/analysis* ; Liver/metabolism* ; Powders ; Rats ; Rats, Sprague-Dawley ; Swine ; Taurodeoxycholic Acid/metabolism* ; Ursidae/metabolism* ; Ursodeoxycholic Acid/metabolism*

Objective: To examine the effect of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) for atherosclerotic lesions in no-stenting zones (NSZ) of the lower extremity. Methods: From June 2019 to December 2021, 46 patients who underwent ELA combining with DCB in lesions of NSZ at Zhongshan Hospital, Fudan University and Jinshan Hospital, Fudan University were retrospectively enrolled, including 29 males and 17 females. The age was (72.5±11.7) years (range: 42 to 93 years). Among them, 44 lesions (95.7%, 44/46) were in popliteal artery and 2 lesions (4.3%, 2/46) were in common femoral artery. Chronic total occlusion (CTO) was observed in 31 patients (76.4%, 31/46), and stenotic lesions were observed in 15 patients (32.6%, 15/46). The length of lesions was (7.3±2.7) cm (range: 3.0 to 13.2 cm). Patients were followed at 6, 12 months after surgery and every year thereafter, and they underwent Doppler and CT angiography examination at each follow-up point. The primary endpoint was primary patency. The secondary endpoints included major amputation-free survival (MAFS) rate, technical success, bailout stent, ankle-brachial index (ABI), target lesion reintervention (TLR). Student t test was applied to compare the difference between ABI of 6 or 12 months after surgery and the baseline. Primary patency, freedom from TLR, and MAFS rate were calculated by Kaplan-Meier method. Results: The technical success rate was 91.3% (42/46). The rate of procedure-related complication was 6.5% (3/46), and all the complications were distal embolization. The rate of flow-limiting dissection was 8.7% (4/46). ABI was significantly increased at 6 and 12 months compared to preoperatively (0.90±0.10 vs. 0.42±0.10, t=-4.48, P<0.01; 0.87±0.12 vs. 0.42±0.10, t=-5.21, P<0.01). The follow-up time[M(IQR)] was 22.5 (8.8) months (range: 6 to 32 months). TLR was performed in 4 patients (4/46, 8.7%). The 2-year primary patency was 86.2% (95%CI: 71.8% to 93.5%). The 2-year freedom from TLR and MAFS rate were 90.7% (95%CI: 77.0% to 96.4%) and 97.8% (95%CI: 85.6% to 99.7%), respectively. Conclusion: ELA combining with DCB can be applied to treat atherosclerotic lesions in NSZ.
Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Arteries ; Laser Therapy