Objective: To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019. Methods: The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted. Results: There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019. Conclusions Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

OBJECTIVE: To evaluate short-term clinical results of fixed-bearing unicompartmental knee arthroplasty (UKA) for patients with medial compartmental knee osteoarthritis. METHODS: From January 2015 to December 2017, 62 patients with medial compartmental knee osteoarthritis were treated by fixed-bearing UKA. Among them, including 19 males and 43 females, aged from 47 to 83 years old with an average of (65.3±8.2) years old. The courses of disease ranged from 5 to 72 months with an average of(19.4±14.3) months. Postoperative complications were observed, VAS score was used to observe degree of pain relief, Hospital for Special Surgery(HSS) score was used to evaluate clinical effects. RESULTS: All patients were followed up from 4 to 40 months with an average of(19.9 ±10.2) months. The incision healed well without blood transfusion, hospital stays ranged from 2 to 10 days with an average of (3.5±1.6) days. No deep infection, dislocation, loosing or per prosthetic fracture occurred after operation, while 1 patient suffered from posterior tibial vein thrombosis. HSS score improved from 69.9±7.2 before operation to 90.1±7.4 at final following-up, and 51 patients obtained excellent results, 9 patients good and 2 moderate. VAS score decreased from 3.8±0.9 before operation to 1.1±0.9 at final following-up. CONCLUSIONS Fixed-bearing UKA for medial compartmental knee osteoarthritis could obtain short-term clinical results for shorter hospital stay, less complications. with fewer complication and fast recovery.
Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; Female ; Humans ; Knee Joint ; Length of Stay ; Male ; Middle Aged ; Osteoarthritis, Knee ; surgery ; Treatment Outcome

OBJECTIVE: To analyze and evaluate the clinical outcomes of enhanced recovery after surgery(ERAS) for hemiarthroplasty for the treatment of femoral neck fractures in elderly patients. METHODS: From January 2015 to December 2016, 466 patients with femoral neck fractures were admitted in our department. Among them, 154 patients were more than 80 years old, with an average age of (83.9±3.2) years old (ranged, 80 to 96 years old), including 27 males and 127 females. According to Garden classification system, 68 cases were type III and others were type IV. ERAS for hemiarthroplasty were performed for all the patients. The time before operation, blood transfusion rate, complications rate, lenth of stay and Harris score system were evaluated. RESULTS: Among 154 patients, 142 patients were followed up, with an average duration of 24.6 months(ranged, 14 to 38 months). Thirty-two patients (20.8%) completed the operation within 48 hours after admission, 67 patients(43.5%) completed the operation within 72 hours after admission, 76 patients(49.4%) discharged within 48 hours after operation, and the blood transfusion rate was 15.9%. One patient was re-hospitalized because of prosthetic dislocation. The re-hospitalization rate was 0.6%. No other patients were re-hospitalized because of superficial or deep infection or periprosthetic fracture. At the latest follow-up, the Harris hip score was 90.2±7.1, 106 patients got an excellent result, 23 good and 9 fair. CONCLUSIONS ERAS for hemiarthroplasty can effectively shorten hospitalization time, relieve pain, reduce blood transfusion rate, reduce postoperative complications, and do not increase the readmission rate of elderly patients with femoral neck fracture, which can achieve good clinical efficacy.
Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Female ; Femoral Neck Fractures ; Fracture Fixation, Internal ; Hemiarthroplasty ; Humans ; Male ; Treatment Outcome

OBJECTIVE: To investigate the effect of moderate-intensity aerobic exercise on the differential expression of rat atrial muscle Proteomics and genes, which provide research basis for the rehabilitation of chronic cardiovascular diseases and exercise -induced cardiac remodeling research. METHODS: Twenty male SD rats were randomly divided into control group and experimental group (=10) according to body weight. Rats in the experimental group were trained (6 days per week),which lasted for 4 weeks of moderate-intensity aerobic exercise at a rate of 24 m·min for 40 min (load intensity equivalent to 60%~70% VO). The proteins were separated by two dimensional gel electrophoresis, and the tandem time-of- flight mass spectrometer technique was used to identify 13 candidate target protein spots. The expression levels of these 13 protein spots were up-regulated more than 5 times or down -regulated to below 1/5. The mRNA of six target proteins were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: By software analysis, the experimental group compared with the control group, there were 8 protein points which their expression reduced more than 4/5 and 5 protein points up-regulated more than 5 times, 13 proteins were identified by mass spectrometry protein spots, the final identification results acquired 8 proteins and a unknown protein of molecular mass 54 KDa, such as:pyruvate dehydrogenase E1α1, mitochondrial aconitate hydratase, protein disulfide isomerase A3, methylmalonic acid semialdehyde dehydrogenase, mitochondrial dihydrolipoic acid dehydrogenase, isovaleryl coenzyme A dehydrogenase, glutathione synthetase, mitogen-activated protein kinase 3 and so on. Compared with the control group, the mRNA expression of methylmalonic acid semialdehyde dehydrogenase in the atrial muscle of rats was decreased after 4 weeks of moderate aerobic exercise (<0.05), the mRNA expression levels of mitochondria Ⅱ lipoic acid dehydrogenase, protein disulfide isomerase A3, mitochondrial aconitate hydratase and glutathione synthetase were decreased (>0.05); The mRNA expression level of isopentenyl-CoA dehydrogenase was increased (>0.05). The results indicated that the mRNA expression level was not completely consistent with the changes in mass spectrometry identification results. CONCLUSIONS The 4 weeks moderate-intensity aerobic exercise induced ignificant changes of rats atrial muscle protemics. The majority of the 13 identified target proteins in this experiment are energy metabolism enzymes. The majority of the expression of the target protein and the mRNA expression in the atrial muscle is inconsistent and different. Exercise may affect the regulation of gene transcription or downstream translation and modification of these target proteins, resulting in the change of differential expression.
Animals ; Electrophoresis, Gel, Two-Dimensional ; Male ; Muscles ; Physical Conditioning, Animal ; Proteomics ; Rats ; Rats, Sprague-Dawley

The qualitative analysis method of RRLC-Q-TOF-MS/MS was established for determine the chemical constituents in Qige Keli. Kramosil C₁₈ column (4.6 mm×150 mm, 3.5 μm) was used at the temperature of 30 °C. The mobile phase was 0.2% formic acid and acetonitrile by gradient elution, with a flow rate at 1.0 mL·min⁻¹, and the injection volume was 10 μL. The high-resolution quadrupole time-flight mass spectrometry was used as detector with electrospray ion source in both positive and negative models. On the basis of medicinal materials, reference materials, literature reports, and mass spectrometry data, the chemical composition in the Qige Keli was identified. A total of 44 compounds were identified, including 3 flavonoids, 21 flavonoid glycosides, 8 organic acids, 6 lactones, and 3 saponins. The results laid the foundation for the quality control of Qige Keli and the further research on pharmacodynamic materials.
Acids ; analysis ; Drugs, Chinese Herbal ; chemistry ; Flavonoids ; analysis ; Glycosides ; analysis ; Lactones ; analysis ; Phytochemicals ; analysis ; Saponins ; analysis ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

BACKGROUND: The stress distribution is different between implants and natural teeth, and the biomechanical characters of implant-natural tooth supported fixed partial dentures need to be explored.OBJECTIVE: To analyze the distributions of stress and strain on the implant interface and natural tooth ligaments by loading a vertical force to a single implant crown, natural tooth crown and a implant-natural tooth supported fixed partial denture.METHODS: Two male healthy Beagle dogs were selected, and their right mandibular first molars were exacted under general anesthesia. Three months later, a 3.3 mm×10 mm RN ITI implant was implanted into the defect region of each dog. The dogs were killed under anesthesia after another 3 months to remove the mandible. One dog was restored by a single implant and natural tooth crown, and the other was restored by the implant-natural tooth supported fixed partial dentures. The specimens were fixed to the load device after embedded with self caring acrylic resin, and the strain gauges were pasted to the cortical bone around the implant and natural tooth neck. The vertical force was loaded to the implant, natural tooth and fixed denture with 40, 60, 80,120, and 160 N.RESULTS AND CONCLUSION: When the force was loaded to the implant of combined denture, the implant stress of combined denture was less than that of the single implant repair, and partial force was loaded on natural teeth; when the force was loaded to the natural tooth of combined denture, the stress to the natural tooth of combined denture was less than that of the single natural tooth repair. When the force was loaded to the natural tooth of combined denture, the stress was assumed by the whole prostheses. However, the stress was almost assumed by the implant when the force was loaded to the implant of combined denture. That is to say, it is feasible to use the implant-natural tooth supported fixed partial dentures.

Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.

Objective To analyze the subtypes and characteristics of HIV-1 among men who have sex with men (MSM) in Zhejiang province from the year 2004 to 2011.Methods Blood DNA/RNA was extracted from the MSM HIV -1 infected individuals and then HIV-1 gag and pol fragments were amplified by nested polymerase chain reaction (nested-PCR)or RT-PCR.The positive PCR products were sequenced and the obtained sequences were analyzed by phylogenetic inference.Results A total of 117 HIV-1 infected MSMindividuals were analyzed,covering 21 provinces according to their household registry.Totally,three major strains were identified including CRF01_AE (84.62%,n =99 ),B (5.98%,n=7)and CRF07_BC (5.13%,n=6). Moreover,3 novel 01B recombinant stains,1 CRF59_01B and 1 CRF08_BC were found.According to the neighbor-joining tree by pol fragments,there were more than 30 sub clusters with bootstrap value higher than 70% among the 84 CRF01_AE sequences.Conclusion CRF01_AE is the major HIV-1 infection strain among MSMin Zhejiang province.CRF59_01B and other novel 01B recombinant stains are first reported among MSM individuals in Zhejiang province.

BACKGROUNDMeningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010.

METHODSThis study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized.

RESULTSThe female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was significantly older than that of grade II or III meningiomas (P < 0.001, Fisher's Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03 and 0.76, respectively; P < 0.001, χ(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series.

CONCLUSIONSFemale predominance was found for benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common subtypes. The cerebral convexity was the most common meningioma location.

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Male ; Meningioma ; epidemiology ; Middle Aged ; Sex Distribution ; Young Adult

OBJECTIVETo examine the recent incidences and trends of childhood malignant solid tumors in Shanghai.

METHODData from the population-based Shanghai Cancer Registry and related retrospective survey were used to analyze the patterns of incidence and trends of malignant solid tumors diagnosed between 2002 and 2010 in children aged 0-14 years. The distributions of incidences were described according to gender, age and cancer types which were classified according to International Classification of Childhood Cancer (ICCC). Annual age-standardized rates (ASRs) were adjusted by the world standard population. Approximate confidence intervals for standardized rate ratios (SRR) based Poisson distribution test-based methods were used to assess changes in incidence over the period 2002 - 2006 and 2007 - 2010.

RESULT(1)A total of 868 cases of childhood malignant solid tumors were diagnosed in Shanghai during 2002 - 2010, accounting for 65.8% of all childhood cancers. The ASR of 2002 - 2010 was 80.2 per million for all solid tumors. (2) The ASR was higher in boys (86.3 per million) than in girls (73.8 per million) with SRR 1.2 (95%CI 1.0 - 1.3). Incidence rate was the highest in the first five years of life with 93.4 per million. The age-specific incidence rates in 5 - 9 and 10 - 14 age groups were 65.2 and 79.3 per million, respectively. (3) CNS tumors, lymphomas, germ cell tumors, neuroblastoma, and soft tissue sarcomas were the top 5 most common solid tumors in children, with the incidence rate of 23.8, 11.0, 7.8, 7.7 and 6.8 per million, respectively. The patterns of subgroups varied in different age groups. Blastomas, such as neuroblastoma, retinoblastoma, were more common in the children aged 0 - 4 years, whereas epithelial carcinomas and bone tumors developed more frequently in elder children aged 10 - 14 years. (4) Compared with the ASR in 2002 - 2006, the ASR for both genders in 2007 - 2010 had no substantial changes (78.7 per million in 2002 - 2006 and 82.9 per million in 2007 - 2010). However, among boys, the incidence rate in 2007 - 2010 was significantly higher than that in 2002 - 2006 with SRR 1.2 (95%CI: 1.0 - 1.4). For specific subgroups of cancer, there were no substantial changes. Some cautions should be taken when interpreting results involving a small number of cases per year and those with wide 95% confidence intervals.

CONCLUSIONThe incidence rate of pediatric malignant solid tumors among males was higher than females during 2002 - 2010, and it differed among different age groups with the highest in the first five years of life. CNS tumor was the most common type of solid tumors in children. This was a unique characteristics comparing with adult reflected in disease spectrum and age of onset. The patterns of incidence and its trends for childhood malignant solid tumors in Shanghai could provide a basis for etiologic research and preventive interventions. The findings also suggest an urgent need for longer population-based surveillance to verify the pattern and changing trends.

Adolescent ; Age Distribution ; Central Nervous System Neoplasms ; epidemiology ; pathology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Germinoma ; epidemiology ; pathology ; Humans ; Incidence ; Infant ; Lymphoma ; epidemiology ; pathology ; Male ; Neoplasm Staging ; Neoplasms ; classification ; epidemiology ; pathology ; Registries ; Risk Factors ; Sex Distribution ; Time Factors ; Urban Population