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.

PURPOSE: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. MATERIALS AND METHODS: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens. Comparison of ACD4Cs as a continuous parameter in different groups was calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: Stage III/IV, B symptoms, elevated lactate dehydrogenase, monocytopenia, high-intermediate and high risk International Prognostic Index (IPI) and Korean Prognostic Index (KPI), high risk Prognostic Index of Natural Killer Lymphoma (PINK), and lower lymphocytes were significantly associated with low ACD4C at diagnosis. With a median follow-up time of 32 months, patients who had an ACD4C < 0.30×109/L had a worse OS. Median OS was 11 months and median PFS was 5 months in the low ACD4C cohort. There were significant differences in both OS and PFS between the two cohorts. Moreover, multivariate Cox analysis identified ACD4Cs as an independent predictor for OS and PFS. CONCLUSION: Low ACD4Cs were associated with poorer survival and could act as a negative predictor for ENKTL patients treated with asparaginase-based regimens.
Cell Count* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase ; Lymphocyte Subsets ; Lymphocytes ; Lymphoma* ; Lymphoma, Extranodal NK-T-Cell ; Lymphoma, Non-Hodgkin ; Medical Records ; Multivariate Analysis ; Prognosis* ; Retrospective Studies ; T-Lymphocytes

Objective To explore effect of cannabinoid receptor type 2(CB2R)on the expression of autophagy-related proteins LC3 and Beclin-1 in the hippocampal CA1 region of rats with status epilepticus ( SE). Methods SE model was established by treating lithium chloride-pilocarpine intraperitoneally injection in Sprague-Dawley(SD) rats. All the rats were randomly divided into four groups including Control group, Epilepsy group,Epilepsy + JWH-133 group and Epilepsy + AM630 group. JWH-133, AM630, and DMSO were injected 60 min before pilocarpine injection by intracerebroventricular injection ( Control group and Epilepsy group with DMSO,Epilepsy+JWH-133 group with JWH-133 and Epilepsy+AM630 group with AM630). At 24 h after SE,the epileptic symptoms were observed. HE staining was performed to observe the number changes of neurons in the hippocampal CA1 region. The spatiotemporal expressions of LC3 and Beclin-1 in the hippocampal CA1 region were observed using Double-label immunofluorescence and Western blot. Results Epileptic symptoms showed that rats in the control group had no obvious epileptic seizures. Those in Epilepsy group presented seizures about (13. 50 ± 0. 61)min after treated with pilocarpine and racine scale was (4. 33 ± 0. 47) scores. The latency period in Epilepsy+JWH-133 group was(19. 33 ± 0. 42) min and longer than that in the Epilepsy group(P<0. 05);Racine scale in Epilepsy+JWH-133 group was 3. 33 ± 0. 59 and less than the Epilepsy group( P<0. 05). The opposite effect was observed in Epilepsy+AM630 group. HE staining showed that compared with the Epilepsy group,the number of the hippocampal CA1 neu-rons increased in Epilepsy+JWH-133 group and decreased in Epilepsy+AM630 group. Immunofluorescence and Western blot showed that LC3 and Beclin-1 were mainly expressed in neurons,and the expression of LC3 and Beclin-1 in Epilepsy group were up-regulated dynamically than that in the control group at 24 h after SE (P<0. 05). Furthermore compared with the Epilepsy group,the expression of LC3 and Beclin-1 in Epilepsy+JWH-133 group were higher but lowered in Epilepsy+AM630 group. Conclusion We demonstrate that CB2R may play a role in autophagy of the hippocampal neurons at the early stage of pilocarpine-induced SE and hinted CB2R may become a treatment target for epilepsy.

To explore influence of ultrasound‐guided lauromacrogol foam sclerotherapy on peripheral blood levels of counting of endothelial cells (CEC) , endothelin (ET)‐1 and nitric oxide (NO) in patients with sa‐phenous vein varicosis .Methods : A total of 90 patients with saphenous vein varicosis were randomly and equally di‐vided into lauromacrogol group (received ultrasound‐guided lauromacrogol foam sclerotherapy ) and routine treat‐ment group (received routine stripping ).Peripheral blood levels of CEC , ET‐1 and NO were observed and com‐pared between two groups before and after surgery , and therapeutic effect and incidence of complications were eval‐uated.Results : Compared with routine treatment group , there were significant reductions in surgery time [ (81. 79 ± 16.88) min vs .(40.55 ± 10. 19) min] , hospitalization time [(3.94 ± 1.36) d vs.(2. 17 ± 1.31) d] and hospital‐ization fee [ (7640. 15 ± 1025.11) RMB vs.(3998.89 ± 910. 67 ) RMB ] in lauromacrogol group , P＝ 0.001 all. Compared with routine treatment group after surgery , there were significant reductions in incidence rate of total complications (17.78% vs .4. 44%) , percentage of patient＇s condition class IV (17. 78% vs.4.44%) , peripheral blood levels of CEC [ (5562. 48 ± 1194. 73)／L vs.(4655.87 ± 1209. 88)／L] and ET‐1 [ (70. 32 ± 10.30) ng／L vs. (62.95 ± 13.78) ng／L] , and significant rise in percentage of patient’ s condition class I (6.67% vs.25. 00%) and peripheral blood NO level [(1.27 ± 0.42) μmol／L vs.(1. 59 ± 0.51) μmol／L] in lauromacrogol group , P＜0. 05 or＜0. 01. Conclusion : Ultrasound‐ guided lauromacrogol foam sclerotherapy can significantly increase therapeutic effect , improve vascular endothelial function in patients with saphenous vein varicosis .And its complications are few .

OBJECTIVE: To carry out the methodological quality evaluation and content analysis of the evidence-based clinical practice guidelines for acupuncture-moxibustion in China, and to provide reference for the development and updating of future guidelines. METHODS: With Appraisal of Guidelines for Research and EvaluationⅡ(AGREEⅡ), 20 evidence-based clinical practice guidelines for acupuncture and moxibustion in China were evaluated from six aspects: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence. In addition, the contents of 20 guidelines were systematically analyzed, and the characteristics of guidelines were summarized from the aspects of disease selection, operation technology type and safety. RESULTS: The scores of six domains were scope and purpose (91.1%), stakeholder involvement (68.5%), rigour of development (68.6%), clarity of presentation (90.3%), applicability (34.5%) and editorial independence (16.7%). The recommendations of the 20 acupuncture guidelines covered common clinical problems such as diagnosis, treatment and precautions, which were in line with the clinical characteristics of acupuncture and moxibustion in terms of content structure. CONCLUSION The methodology of the evidence-based clinical practice guidelines for acupuncture and moxibustion in China conformed to the requirements of AGREEⅡ on the quality evaluation, and the overall quality was moderate, but the aspects of applicability and editorial independence were still needed to be improved. The contents of recommendations in 20 guidelines were specific and clear, in line with the characteristics of acupuncture and moxibustion, presenting clinical reference value. In the future, in the process of guideline development, the method of developing acupuncture and moxibustion guidelines should be constantly improved to improve the quality of the guidelines; in the meantime, more attention should be paid to the generalization and clinical applicability evaluation.
Acupuncture Therapy ; China ; Evidence-Based Medicine ; Evidence-Based Practice ; Humans ; Moxibustion

OBJECTIVE: To observe the correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases. METHODS: In clinical research, 443 patients from 8 hospitals were recruited, including the outpatients and inpatients of Crohn's disease (=143), ulcerative colitis (=108), chronic appendicitis (=87) and other intestinal diseases (=105). The site with tenderness on the body surface and the morphological changes of local skin were observed and recorded in the patients. Using a sensory tenderness instrument, the pain threshold at the sensitization point was measured in 60 patients with ulcerative colitis. In animal experiment, SD rats were used and divided into a enteritis group (=8), in which the enteritis model were established, and a control group (=3), in which no any intervention was given. After the injection of Evans blue (EB) at caudal vein, the blue exudation points on the body surface were observed and the distribution rule was analyzed statistically. RESULTS: The referred pain on the body surface in the patients with intestinal diseases was mainly located in the lower abdomen (93.9%, 416/443), the lumbar region (70.9%, 314/443) and the lower legs (33.0%, 146/443). The diameter of tenderness region was 1.5 to 2.5 cm. Compared with the region without sensitization, the pain threshold of the sensitization point in the patients with ulcerative colitis was reduced significantly (<0.001). The referred pain on the body surface in the patients with appendicitis was located in the right lower abdomen (97.7%, 85/87), the waist and back (54.0%, 47/87) and the right lower limbs on the medial side (71.3%, 62/87). The tenderness region was 1 to 2 cm in diameter and was irregular in form. After modeling of enteritis in the rats, the EB exudation points were visible from T to L. CONCLUSION Intestinal diseases induce referred pain on the body surface where is the same as or adjacent to the location of the spinal segment corresponding to the affected intestinal section. These sensitization regions are related to the locations of acupoints.
Acupuncture Points ; Animals ; Colitis, Ulcerative ; Humans ; Intestinal Diseases ; Pain Threshold ; Pain, Referred ; diagnosis ; therapy ; Rats ; Rats, Sprague-Dawley ; Sensation

Professor is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between and . While regulating and , more attention should be paid to - harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.
Acupuncture Points ; Acupuncture Therapy ; Breast Neoplasms ; surgery ; Female ; Hot Flashes ; therapy ; Humans ; Syndrome

PURPOSE: Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients. MATERIALS AND METHODS: In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients. RESULTS: The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70. CONCLUSION: These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.
B-Lymphocytes ; Diagnosis ; Fibrinogen ; Humans ; Inflammation ; Leukemia, Lymphocytic, Chronic, B-Cell ; Lymphoproliferative Disorders ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Serum Albumin

PURPOSE: The purpose of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans. MATERIALS AND METHODS: The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET-CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5, and 3.0 thresholding method, respectively. RESULTS: Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 476.4 (sensitivity, 85.7%; specificity, 78.0%; area under the curve [AUC], 0.760; p=0.003) and 2,676.9 (sensitivity, 71.4%; specificity, 78.0%; AUC, 0.760; p=0.003). On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (hazard ratio [HR], 5.406; 95% confidence interval [CI], 1.326 to 22.040; p=0.019 and HR, 6.502; 95% CI, 1.079 to 39.182; p=0.042) and overall survival (OS) (HR, 4.111; 95% CI, 1.125 to 15.027; p=0.033 and HR, 5.885; 95% CI, 1.014 to 34.148; p=0.049). ROC curve analysis showed the optimal cut-off values for ΔTMTV3.0 and ΔTLG3.0 were 66.3% (sensitivity, 85.7%; specificity, 63.4%; AUC, 0.774; p < 0.001) and 64.5% (sensitivity, 85.7%; specificity, 65.9%; AUC, 0.777; p < 0.001). CONCLUSION: Baseline TMTV and TLG are strong predictors of PFS and OS in FL. Furthermore, interim TMTV (ΔTMTV > 66.3%) and TLG (ΔTLG > 64.5%) reduction are valuable tools for early treatment response assessment in FL patients.
Area Under Curve ; Disease-Free Survival ; Electrons ; Glycolysis ; Humans ; Lymphoma, Follicular ; Methods ; Prognosis ; ROC Curve ; Sensitivity and Specificity ; Tumor Burden

After a long-term co-evolution, alphaherpesviruses have established mutual adaptability with their hosts. Some alphaherpesviruses have typical neurotropic characteristics, which have received extensive attention and in-depth research. Neurotropic alphaherpesviruses can break through the host barrier to infect neurons and multiply in large numbers in the neuron cell body to complete further proliferation or establish latent infection in the cell body. Either in the process of infecting neurons or further spreading, alphaherpesviruses will undergo transmission along axons or dendrites, so this process is an integral part of the life cycle of the viruses, and is also a key factor for the viruses to spread in nervous system. Therefore, studies on transportation of alphaherpesviruses in neurons will provide new insights of the viruses and promote the development of corresponding vaccines or targeted therapeutic pharmaceuticals. In addition, the neurotropism of alphaherpesviruses is conducive to the analysis of nerve circuits. Herein, the mechanisms of alphaherpesvirus transport in axons were reviewed, and the research direction and application of the transport of alphaherpesviruses in axons were put forward, which can provide reference for the prevention and control of alphaherpesviral infections.
Alphaherpesvirinae ; Axons ; Neurons