Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

Objective: To explore the long-term efficacy of laparoscopic-assisted anorectoplasty and conventional anorectoplasty in the treatment of children with high and middle anal atresia. Methods: A retrospective cohort study was used. Inclusion criteria: (1) children with high and middle anal atresia; (2) complicated with rectourethral or rectovesical fistula; (3) complete follow-up data. Exclusion criteria: (1) complicated with 21-trisomy; (2) cerebral palsy and other mentaldisabilities; (3) Currarino syndrome; (4) FG syndrome. Clinical data of 88 patients with middle and high anal atresia, who complicated with rectourethral fistula or rectovesical fistula, and underwent anoplasty at Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from January 2009 to June 2014 were enrolled in the study and analyzed. There were 24 cases with middle atresia and 64 cases with high atresia. All the cases were divided into 2 groups based on the operative method: laparoscopic group (laparoscopic-assisted anorectoplasty, 49 cases), pena group (posterior sagittal anorectoplasty, 39 cases). The demographic features of two groups were comparable. There were no statistically significant differences in gender, age, body mass, classification of anomaly types and sacral ratio (all P>0.05). Student t test and Chi square tests were used to compare the surgical conditions (operative time, postoperative hospital stay and complications), anal function (Kelly score), constipation (Krickenbeck constipation score) and anorectal pressure. Results: Children of both groups all completed operation ssuccessfully. There were no statistically significant differences between laparoscopic group and pena group in the operative time [(120±31) minutes vs. (112±23) minutes, t=1.343, P=0.091] and postoperative hospital stay [(7.1±2.3) days vs. (10.7±3.3) days, t=6.021, P=1.000]. Complications were more common in the pena group [16.3% (8/49) vs. 35.9% (14/39), χ²=4.436, P=0.035]. The main complications in laparoscopic group were anal prolapse (8.2%, 4/49) and anal stenosis (6.2%, 3/49), while in pena group were anal stenosis (12.8%, 5/39) and perioperative perianal skin erosion (10.3%, 4/39). As for the anal function, the degree of feces, defecation control and sphincter contractility, the single scoring differences of Kelly scoring system were not statistically significant between the two groups, but the proportion of good function in the laparoscopic group was higher than that in the pena group [67.3% (8/49) vs. 38.5% (15/39), χ²=7.308, P=0.007]. Constipation occurred in 6 (12.2%) patients in the laparoscopic group, of whom 5 were improved by diet regulation and 1 required laxatives, while 9 (23.1%) patients developed constipation in the pena group, of whom 4 were improved by diet regulation and 5 required long-term laxatives. The difference of constipation ratio was not statistically significant (χ²=1.802, P=0.180). There were no cases of Krickenbeck constipation grade 3. Compared to the pena group, the laparoscopic group had higher anal resting pressure [(33.35±9.69) mmHg vs. (27.68±10.74) mmHg, t=2.599, P=0.011], higher dilating pressure [(9.00±5.61) mmHg vs.(6.51±3.24) mmHg, t=2.462, P=0.016], higher maximal squeeze pressure [(65.80±17.23) mmHg vs. (56.74±18.93) mmHg, t=2.389, P=0.019] and longer maximal contraction time [(21.16±5.02) seconds vs. (18.44±7.24) seconds, t=2.079, P=0.041]. The rectal resting pressure [(5.36±3.00) mmHg vs. (4.61±3.93) mmHg, t=1.015, P=0.312] was not statistically significantly different. Conclusions Compared with posterior sagittal anorectoplasty, laparoscopic-assisted anorectoplasty in the treatment of high and middle anal atresia has better long-term efficacy with less perioperative complications.

Abstract　　The promyelocytic leukemia (PML) gene encoded PML protein as a tumor suppressor protein, plays important roles in the occurrence and development of various cancers including acute promyelocytic leukemia. Recent studies have indicated that there are a variety of post-translational modifications of the PML protein, such as SUMOylation, ubiquitination, phosphorylation, and acetylation in cells. These modifications of the PML protein can directly affect the formation of PML nuclear bodies (PML-NBs), repair DNA damage, and modulate cell apoptosis. Furthermore, the abnormal modifications of PML not only result in the occurrence of hematopoietic tumors, but also are closely related to the drug-resistance of cancer. Therefore, investigating the post-translational modifications of PML is significant to uncover the mechanism of formation and functions of PML-NBs, thus contributing to the prevention and treatment of related hematopoietic tumors. In this review, the characteristics of the post-translational modifications of PML protein and the relationship between these modifications and functions of PML-NBs are summarized so as to provide the potential targets for the treatment of related cancers.
Humans ; Intranuclear Inclusion Bodies ; Leukemia, Promyelocytic, Acute ; Nuclear Proteins ; Promyelocytic Leukemia Protein ; Protein Processing, Post-Translational

Objective To explore the long?term efficacy of laparoscopic?assisted anorectoplasty and conventional anorectoplasty in the treatment of children with high and middle anal atresia. Methods A retrospective cohort study was used. Inclusion criteria: (1) children with high and middle anal atresia; (2) complicated with rectourethral or rectovesical fistula; (3) complete follow?up data. Exclusion criteria: (1) complicated with 21?trisomy; (2) cerebral palsy and other mentaldisabilities; (3) Currarino syndrome; (4) FG syndrome. Clinical data of 88 patients with middle and high anal atresia, who complicated with rectourethral fistula or rectovesical fistula, and underwent anoplasty at Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from January 2009 to June 2014 were enrolled in the study and analyzed. There were 24 cases with middle atresia and 64 cases with high atresia. All the cases were divided into 2 groups based on the operative method: laparoscopic group (laparoscopic?assisted anorectoplasty, 49 cases), pena group (posterior sagittal anorectoplasty, 39 cases). The demographic features of two groups were comparable. There were no statistically significant differences in gender, age, body mass, classification of anomaly types and sacral ratio (all P>0.05). Student t test and Chi square tests were used to compare the surgical conditions (operative time, postoperative hospital stay and complications), anal function (Kelly score), constipation (Krickenbeck constipation score) and anorectal pressure. Results Children of both groups all completed operation ssuccessfully. There were no statistically significant differences between laparoscopic group and pena group in the operative time [(120±31) minutes vs. (112±23) minutes, t=1.343, P=0.091] and postoperative hospital stay [(7.1±2.3) days vs. (10.7±3.3) days, t=6.021, P=1.000]. Complications were more common in the pena group [16.3% (8/49) vs. 35.9% (14/39), χ2=4.436, P=0.035]. The main complications in laparoscopic group were anal prolapse (8.2%, 4/49) and anal stenosis (6.2%, 3/49), while in pena group were anal stenosis (12.8%, 5/39) and perioperative perianal skin erosion (10.3%, 4/39). As for the anal function, the degree of feces, defecation control and sphincter contractility, the single scoring differences of Kelly scoring system were not statistically significant between the two groups, but the proportion of good function in the laparoscopic group was higher than that in the pena group [67.3% (8/49) vs. 38.5% (15/39), χ2=7.308, P=0.007]. Constipation occurred in 6 (12.2%) patients in the laparoscopic group, of whom 5 were improved by diet regulation and 1 required laxatives, while 9 (23.1%) patients developed constipation in the pena group, of whom 4 were improved by diet regulation and 5 required long?term laxatives. The difference of constipation ratio was not statistically significant (χ2=1.802, P=0.180). There were no cases of Krickenbeck constipation grade 3. Compared to the pena group, the laparoscopic group had higher anal resting pressure [(33.35 ± 9.69) mmHg vs. (27.68 ± 10.74) mmHg, t=2.599, P=0.011], higher dilating pressure [(9.00±5.61) mmHg vs.(6.51±3.24) mmHg, t=2.462, P=0.016], higher maximal squeeze pressure [(65.80 ± 17.23) mmHg vs. (56.74 ± 18.93) mmHg, t=2.389, P=0.019] and longer maximal contraction time [(21.16±5.02) seconds vs. (18.44±7.24) seconds, t=2.079, P=0.041]. The rectal resting pressure [(5.36 ± 3.00) mmHg vs. (4.61 ± 3.93) mmHg, t=1.015, P=0.312] was not statistically significantly different. Conclusions Compared with posterior sagittal anorectoplasty, laparoscopic?assisted anorectoplasty in the treatment of high and middle anal atresia has better long?term efficacy with less perioperative complications.

Objective To explore the long?term efficacy of laparoscopic?assisted anorectoplasty and conventional anorectoplasty in the treatment of children with high and middle anal atresia. Methods A retrospective cohort study was used. Inclusion criteria: (1) children with high and middle anal atresia; (2) complicated with rectourethral or rectovesical fistula; (3) complete follow?up data. Exclusion criteria: (1) complicated with 21?trisomy; (2) cerebral palsy and other mentaldisabilities; (3) Currarino syndrome; (4) FG syndrome. Clinical data of 88 patients with middle and high anal atresia, who complicated with rectourethral fistula or rectovesical fistula, and underwent anoplasty at Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from January 2009 to June 2014 were enrolled in the study and analyzed. There were 24 cases with middle atresia and 64 cases with high atresia. All the cases were divided into 2 groups based on the operative method: laparoscopic group (laparoscopic?assisted anorectoplasty, 49 cases), pena group (posterior sagittal anorectoplasty, 39 cases). The demographic features of two groups were comparable. There were no statistically significant differences in gender, age, body mass, classification of anomaly types and sacral ratio (all P>0.05). Student t test and Chi square tests were used to compare the surgical conditions (operative time, postoperative hospital stay and complications), anal function (Kelly score), constipation (Krickenbeck constipation score) and anorectal pressure. Results Children of both groups all completed operation ssuccessfully. There were no statistically significant differences between laparoscopic group and pena group in the operative time [(120±31) minutes vs. (112±23) minutes, t=1.343, P=0.091] and postoperative hospital stay [(7.1±2.3) days vs. (10.7±3.3) days, t=6.021, P=1.000]. Complications were more common in the pena group [16.3% (8/49) vs. 35.9% (14/39), χ2=4.436, P=0.035]. The main complications in laparoscopic group were anal prolapse (8.2%, 4/49) and anal stenosis (6.2%, 3/49), while in pena group were anal stenosis (12.8%, 5/39) and perioperative perianal skin erosion (10.3%, 4/39). As for the anal function, the degree of feces, defecation control and sphincter contractility, the single scoring differences of Kelly scoring system were not statistically significant between the two groups, but the proportion of good function in the laparoscopic group was higher than that in the pena group [67.3% (8/49) vs. 38.5% (15/39), χ2=7.308, P=0.007]. Constipation occurred in 6 (12.2%) patients in the laparoscopic group, of whom 5 were improved by diet regulation and 1 required laxatives, while 9 (23.1%) patients developed constipation in the pena group, of whom 4 were improved by diet regulation and 5 required long?term laxatives. The difference of constipation ratio was not statistically significant (χ2=1.802, P=0.180). There were no cases of Krickenbeck constipation grade 3. Compared to the pena group, the laparoscopic group had higher anal resting pressure [(33.35 ± 9.69) mmHg vs. (27.68 ± 10.74) mmHg, t=2.599, P=0.011], higher dilating pressure [(9.00±5.61) mmHg vs.(6.51±3.24) mmHg, t=2.462, P=0.016], higher maximal squeeze pressure [(65.80 ± 17.23) mmHg vs. (56.74 ± 18.93) mmHg, t=2.389, P=0.019] and longer maximal contraction time [(21.16±5.02) seconds vs. (18.44±7.24) seconds, t=2.079, P=0.041]. The rectal resting pressure [(5.36 ± 3.00) mmHg vs. (4.61 ± 3.93) mmHg, t=1.015, P=0.312] was not statistically significantly different. Conclusions Compared with posterior sagittal anorectoplasty, laparoscopic?assisted anorectoplasty in the treatment of high and middle anal atresia has better long?term efficacy with less perioperative complications.

Objective:The main objective of this study is to evaluate the efficiency of China's heath resources al-location during 2004 to 2015 under the constraint of medical expenses control. Methods:To evaluate the efficiency of China's heath resources allocation,the undesired output Slacks-Based Measure(SBM) model was used. Results:As per the findings of this study,the efficiency of heath resources allocation at the national and regional levels of the undesired output SBM model was significantly lower than that of the traditional CCR model during 2004 to 2015. The non-expec-ted output redundancy rate and expected output deficiency rate at the national and regional levels were much greater than the input redundancy rate of health resources allocation of the national and regional levels. In addition,with re-dundancy rate introduction,the losses of health resource allocation efficiency in different provinces within the region were not the same. Conclusions:The efficiency of China's heath resources allocation was overestimated by the tradition-al DEA model,which was less sensitive to the change in its characteristics..Giving priority to non-expected output re-dundancy and expected output deficiency are the main reasons for the loss of health resource allocation in china,and are considered as internal and external improvement priorities for the performance of health resource allocation. It was suggested to establish the performance evaluation system of health resource allocation,which includes the integration of health resources input,expected-output and non-expected output,and evaluation techniques;and a mechanism for per-formance assessment and evaluation,supervision and feedback of health resource allocation should be established;and improve the implication of regional medical and health planning policies.