ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.
Mice ; Animals ; Bone Marrow Transplantation ; Bone Marrow ; Mice, Inbred C57BL ; Hematopoietic Stem Cells ; Bone Marrow Diseases ; Hematopoietic Stem Cell Transplantation ; Mice, Inbred BALB C

Objective:To explore the effects of Baduanjin and balancer exercise on motor and non-motor symptoms for patients with mild to moderate Parkinson's disease (PD). Methods:From May, 2017 to September, 2018, 31 patients with PD were collected from the inpatients, outpatients and outside of our hospitals. The patients accepted Baduanjin and balancer exercise successively, three weeks for each exercise, and were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III and IV, and Non-motor Symptoms Scale (NMSS) before and after each exercise. Results:Four cases dropped out during Baduanjin exercise. The total score, the scores of part I, II and III of MDS-UPDRS, and NMSS score (t > 3.274, P < 0.01) decreased significantly after Baduanjin exercise. Other three cases dropped out during balancer exercise. The total score and the score of part III of MDS-UPDRS decreased significantly after balancer exercise (t > 2.763, P < 0.05). Conclusion:Baduanjin exercise can improve the motor and non-motor symptoms of mild to moderate PD, but not significant for motor complications; while balancer exercise can improve the motor symptoms, but not significant for non-motor symptoms and motor complications.

To establish the UPLC fingerprint of Zhongyi Angong Niuhuang Pills, in order to evaluate its quality by chemical pattern recognition. The method was developed on a column of Poroshell 120 EC-C_(18), with methanol-0.1% formic acid solution as the mobile phase for gradient elution at a flow rate of 0.4 mL·min~(-1). The column temperature was 30 ℃,and the detective wavelength was 254 nm. The similarity of 24 batches of Angong Niuhuang Pills was compared by using Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2004 A). Hydrophobic cluster analysis,principal components analysis and partial least squares discriminant analysis were conducted by using SIMCA 13.0 software to investigate different components among these products. The UPLC characteristic fingerprint was established in this study. And 17 common peaks were identified by standard reference and UPLC-MS. The similarity of 24 batches samples were above 0.980,which can be classified into three categories for pattern recognition. Baicalin,berberine,jatrorrhizine,wogonin and wogonoside were identified as the main markers that cause differences of various batches. The method is simple,rapid,accurate and reproducible,and can provide scientific basis for improving the quality standard of Zhongyi Angong Niuhuang Pills.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry

Objective: To investigate the familial cytomolecular genetics of an infertile male. METHODS: We analyzed the clinical phenotypes and karyotypes of three males from the family of an infertile man, detected the sequence-tagged sites (STS) in the AZF deletions of the Y chromosome by multiplex polymerase chain reaction (PCR), and identified the target genes by multiplex ligation-dependent probe amplification (MLPA). RESULTS: The karyotypes of the proband and his brother were 46, XY, inv (19) (p13.3q13.1) and that of his father was 46, XY. The three males were all carriers of AZFc deletion of the Y chromosome, and all found with the same reduction of the gene copy number in the AZFb and AZFc regions. CONCLUSIONS Combined use of karyotype analysis, Y chromosome STS PCR, and MLPA revealed the genetic causes of the male infertile family.

OBJECTIVETo discuss the surgical method and clinical efficacy for open tarsometatarsal joint injuries.

METHODSFrom March 2011 to January 2015, 21 patients with open tarsometatarsal joint injuries were treated with stage-surgery method, including 14 males and 7 females with an average age of 45.6 years old ranging from 20 to 75 years. Injury site occurred in the left foot of 13 cases and right foot of 8 cases. Traffic injury was in 5 cases, crush injury in 6 cases, heavy crushing was in 10 cases. According to Myerson to classify for tarsometatarsal joint injury, 5 cases were type B2, 9 cases were type C1, and 7 cases were type C2. And according to Gustilo to typing for soft tissue injury, 5 cases were type IIB, 10 cases were type IIIA, 6 cases were type IIIB. Fracture healingand complications were observed after operation and clinical effects were evaluated according to the midfoot score of AOFAS.

RESULTSAll the patients were followed up from 11 to 40 months with an average of 16.2 months. The fracture healing time was from 10 to 16 weeks with an average of 12.3 weeks. No complications such as deep infection, nonunion and osteomyelitis were found. Midfoot score of AOFAS at last follow-up was 83.0±14.9, 9 cases got excellent results, 8 good, 2 fair, 2 poor. Two patients complicated with severe traumatic arthritis once again underwent tarsometatarsal arthrodesis.

CONCLUSIONSFor the treatment of open tarsometatarsal joint injury, reasonable debridement, comprehensive assessment for the soft tissue injury, correctly grasp the surgical indications and time of internal fixation, can reduce the incidence of deep infection and osteomyelitis.

OBJECTIVETo explore individual choice and therapeutic effect of distal fibula internal fixation in treating ankle fractures in elderly.

METHODSFrom May 2012 to April 2015, 68 elderly patients with ankle fractures were treated by surgical operation, included 37 males and 31 females with an average of 69.2 years old ranging from 62 to 81 years. According to Danis-Weber classification, there were 19 cases belong to type A, 31 cases belong to type B, and 18 cases belong to type C. According to Lange-Hanson classification, 22 cases were supinatio-extorsion, 18 were pronate-extorsion, 19 were supinatio-adduction, and 9 were pronate-abduction. All patients were performed individyually with different internal fixation methods for the treatment of distal fibula fracture according to different types of fracture. Clinical results were evaluated based on clinical examination, radiographic evaluation and AOFAS score.

RESULTSTwelve patients were treated with Herbert screw, 7 cases with Kirschner wire tension band, 5 cases with 1/3 tube plate, 6 cases with reconstruction plate, 17 cases with fibular end dissection steel plate composite, and 21 cases with distal fibula anatomic locking plate. All patients were followed up from 12 to 26 months with an average of 17.7 months. The operative incision of all patients were primary healed. And there was no bone nonunion, ankle instability, internal fixation loosening and fracture occurred. Fracture healing time ranged from 2.7 to 4 months with an average of 3.2 months, and had significant differences among different groups(<0.05). There were no statistical differences in AOFAS score, VAS score and motion of ankle joint among different internal fixation groups(>0.05). Dorsal stretch was 6° to 18° with an average of 15°, plantar flexion ranged from 26°to 47° with an average of 37°. AOFAS score at the latest following-up was 88.4±4.3, 34 patients got an excellent result, 30 good and 4 fair.

CONCLUSIONSGood clinical results could be obtained by using individualized internal fixation for distal fibula fracture for the treatment of the ankle fractures in elderly.

OBJECTIVETo investigate the effcacy of the staple fixation for the treatment of hamate metacarpal joint injury.

METHODSFrom May 2009 to November 2012,16 patients with hamate metacarpal joint injury were treated with staple fixation including 10 males and 6 females with an average age of 33.6 years old ranging from 21 to 57 years. Among them, 11 cases were on the fourth or fifth metacarpal base dislocation without fractures, 5 cases were the fourth or fifth metacarpal base dislocation with avulsion fractures of the back of hamatum. Regular X-ray review was used to observe the fracture healing, joint replacement and position of staple fixation. The function of carpometacarpal joint and metacarpophalangeal joint were evaluated according to ASIA (TAM) system evaluation method.

RESULTSAll incision were healed well with no infection. All patients were followed up from 16 to 24 months with an average of (10.0 +/- 2.7) months. No dislocation recurred, the position of internal fixator was good,no broken nail and screw withdrawal were occurred. Five patients with avulsion fracture of the back of hamatum achieved bone healing. The function of carpometacarpal joint and metacarpophalangeal was excellent in 10 cases,good in 5 cases, moderate in 1 case.

CONCLUSIONThe application of the staple for the treatment of hamatometacarpal joint injury has the advantages of simple operation, small trauma, reliable fixation, early postoperative function exercise and other advantages, which is the ideal operation mode for hamatometacarpal joint injury.

Adolescent ; Adult ; Carpal Joints ; injuries ; surgery ; Female ; Fracture Fixation, Internal ; instrumentation ; methods ; Fractures, Bone ; surgery ; Hamate Bone ; injuries ; surgery ; Humans ; Male ; Metacarpal Bones ; injuries ; surgery ; Metacarpophalangeal Joint ; injuries ; surgery ; Middle Aged ; Sutures ; utilization ; Young Adult