BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

OBJECTIVE: Dexmedetomidine (DEX), the most specific α ₂-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. METHODS: We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O ₂) and hypoxic (1% O ₂) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. RESULTS: The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). CONCLUSION We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α ₂-adrenergic receptor mediation might be the critical mechanisms.
Animals ; Humans ; Mice ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Carcinoma, Hepatocellular ; Cardiovascular Physiological Phenomena ; Dexmedetomidine/pharmacology* ; Hypoxia ; Liver Neoplasms/drug therapy* ; Oxygen ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/genetics* ; Receptors, Adrenergic, alpha-2/metabolism*

Humans ; Heart Atria ; Biopsy ; Surgical Instruments ; Catheters ; Lymphoma/pathology*

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Objective:To compare the chemical constituents of Puerariae Flos from three different varieties of Pueraria montana var. lobata， P. montana var. thomsonii and P. montana var. montana. Method:Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-20 min， 10%-30%B； 20-30 min， 30%-55%B； 30-35 min， 55%-95%B； 35-37 min， 95%B； 37-40 min， 95%-10%B）， the flow rate was 0.25 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in positive and negative ion modes with scanning range of m/z 50-1 500. The chemical components from different sources of Puerariae Flos were identified in combination with the chemical composition database and literature information. After the obtained data were normalized by MarkerView^TM 1.2.1， they were imported into SICMA-P 14.1 software for principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） to select the main differentiated components among the three different varieties. Result:A total of 35 compounds were identified from three different varieties of Puerariae Flos， including 22 isoflavones， 6 flavonoids and 7 saponins. The flowers of P. lobata， P. montana var. thomsonii and P. montana var. montana contained 32， 35， 33 compounds， respectively. And 18 differential compounds were screened under the positive and negative ion modes， including kakkalide， tectoridin， 6″-O-xylosyl-tectoridin， 4'-methyltectorigenin-7-glucoside， glycitin， 6″-O-xylosyl-glycitin， irisolidone， kaikasaponin Ⅲ， 6″-O-malonylglycitin， kakkalidone， tectorigenin， rutin， soyasaponin BB， vitexin， biochanin A， genistin， kakkatin， azukisaponin Ⅱ. Conclusion:This research is the first to systematically study the chemical constituents of the flower of P. montana var. montana， although the flower of P. montana var. montana is used as adulterants， it has high contents of tectoridin and 6″-O-xylosyl-tectoridin， which has great potential for development. The efficacy components such as kakkalide and tectoridin in Puerariae Flos from the three sources of varieties are obviously different， and it is necessary to carefully consider the application of these three varieties as Puerariae Flos.

A good neural microenvironment is an important basis for improving the damaged nerves and promoting axonal repair and regeneration. The destruction of neural microenvironment， closely related to the lack of neurotrophic factors， microcirculation disorders and immune abnormalities， is the key pathogenesis leading to diabetic peripheral neuropathy （DPN）. In traditional Chinese medicine， disharmony between Ying and Wei is considered as the key pathology in the development of DPN. It may be manifested as Ying and Wei deficiency， or Ying and Wei impassability， or Ying， Wei， Qi and blood intersection disorders， all of which may cause body fluid condensed into phlegm， blood into blood stasis， further leading to the mutual knot of phlegm and blood stasis， meridian obstruction， numbness and pain of limbs. "Regulating Ying and Wei and tonifying spleen and stomach" is the main therapeutic idea to promote intersection between Ying and Wei and unblock Qi and blood. The method has a significant effect on DPN. However， the current studies on the mechanism of regulating Ying and Wei in the treatment of DPN are still in lack of in-depth discussion， and the studies are mostly limited to the microcirculation disorders. Numerous studies have confirmed that the courses and distribution， physiological characteristics， functions of Ying and Wei are closely related to nerve， immune， metabolic substances and microcirculation. Based on the modern medicine essence of Ying and Wei， the author thinks that the discussion on connotation of the Ying and Wei from the perspective of neural microenvironment has a scientific basis， and regulating Ying and Wei is not only inherited from the traditional Chinese medicine theory， but also conforms to the modern understanding on DPN pathogenesis and treatment. Regulating Ying and Wei and smoothing middle-jiao can improve neural microenvironment and give play to the role of restoring damaged nerve， and its mechanism may be related to regulating neurotrophic factors， immune active substances， metabolites， and microcirculation dysfunction.

Objective: This study aimed to measure the basal energy expenditure (BEE) of Chinese healthy adults and establish an accurate predictive equation for this population. Methods: In total, 470 Chinese healthy adults had their BEE measured using the Cosmed K4b portable metabolic system. Multiple linear regression analysis was applied to develop new optimal equations for predicting BEE. The bias, accuracy rate, concordance correlation coefficient (CCC), and root mean square error (RMSE) were used to evaluate the accuracy of the predictive equations. Results: There was a significant difference in BEE between males and females, with 5,954 kJ/d and 5,089 kJ/d, respectively. People living in rural areas expended significantly higher BEE (5,885 kJ/d) than those in urban areas (5,279 kJ/d). Previous equations developed by Henry, Schofield, Harris-Benedict (H-B), and Liu overestimated the BEE of Chinese healthy adults. The new equations derived from the present study displayed the smallest average bias and RMSE from the measured basal energy expenditure (mBEE). The CCC of the new equations was higher than other predictive equations, but it was lower than 0.8. There was no significant difference in the accuracy rate among all predictive equations. Conclusions Sex and regional differences in BEE were observed in Chinese healthy adults. Neither the widely used previous predictive equations nor the one derived in the present study were accurate enough for estimating the BEE of Chinese healthy adults. Further study is required to develop more accurate equations for predicting the BEE of Chinese healthy adults aged between 20-45 years.
Adult ; Basal Metabolism ; Calorimetry ; methods ; China ; Female ; Humans ; Male ; Young Adult

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
China ; Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human ; Humans ; Male ; Retrospective Studies ; Stomach Neoplasms/etiology*

OBJECTIVE: The aim of this study was to explore the association of dopamine receptor D2 (DRD2) polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up. METHODS: This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical characteristics and DRD2 polymorphisms (including rs1076562, rs2075654, and rs4586205) were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance. RESULTS: One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carriers (68.6% for TC+TT) was higher compared to the major allele homozygote (43.3% for CC). After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carriers for the alleviation of obesity was 3.34 (95% confidence interval (CI): 1.30‒8.58). CONCLUSIONS The rs2075654 polymorphism of DRD2 is related to long-term obesity alleviation in obese Chinese children and adolescents.
Adolescent ; Body Mass Index ; Child ; Female ; Humans ; Male ; Obesity/genetics* ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D2/genetics* ; Retrospective Studies

Objective : To explore the effects of mouth floor approach intubation in the treatment of jaw fracture combined with skull base injury. Methods : From Jan. 2014 to Oct. 2015, 7 cases of jaw fracture combined with skull base injury were selected from Medical center of Stomatology, Foshan Hospital of Traditional Chinese Medicine (FSTCM). All cases were treated with mouth floor approach intubation, because they were not suitable to be given the oral or nasal intubation anesthesia. Results : All the patients healed well after operation, and there was no tube accident or other complications. Conclusions For patients of jaw fracture combined with skull base injury, the mouth floor approach intubation could be recommended as a supplementary choice for traditional intubation methods.