With the remarkable achievements made in the treatment targeted at tumor immune checkpoints, more and more new immunotherapy drugs have been applied to the malignancies treatment. Camrelizumab (AiRuiKa) is a novel human immunoglobulin G4 (IgG4) monoclonal antibody (mAb), which can target the programmed death 1 (PD-1) and block its binding to the programmed death ligand 1 (PD-L1), so as to restore the body's immune function and achieve anti-tumor effect. The drug was officially approved by National Medical Products Administration (NMPA) on May 29, 2019 for use in patients with recurrent or refractory classical Hodgkin's lymphoma (cHL) who are treated with at least second-line systemic therapy. In addition, the drug showed good anti-tumor activity in esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), non-small cell lung cancer (NSCLC), and gastric cancer (GC) and gastroesophageal junction cancer (EGJC). The research progress of camrelizumab on mechanism of action, pharmacodynamics and pharmacokinetics, clinical studies, adverse reactions etc. were reviewed in present paper.

Objective To study the risk factors of hyperthyroid heart diseases(HHD) by analyzing clinical features of patients in order to provide a scientific basis for prevention and treatment of HHD. Methods Nine hundred and eighty two cases were selected as objective from in-patient data of Thyroid Disease Treatment Centre of Shandong Province. The cases were divided into hyperthyroidism group and HHD group. The variables of etiology,sex, age, duration of disease, TSH, FT3, FT4 and TRAb were analyzed by comparative analysis. The risk factors were analyzed by logistic regression. Results The prevalence of hyperthyroidism complicated hyperthyroid heart disease was 7.7%(76/982), age, duration of diseases, FT3, TRAb in the HHD group were [(51.4 ± 11.5), (6.3 ±2.1) years, 21.6 pmol/L, 71.6 U/L], in hyperthyroidism group were [(37.9 ± 9.8), (2.6 ± 1.3) years, 14.9pmol/L, 49.6 U/L]. The differences were statistically significant(u = 9.93,15.23, T = 44954,48792.5, P ＜ 0.05)between the two groups. The factors of the older, higher FT3 and TRAb, longer duration, Graves disease (OR =1.751,1.470,1.483,1.445,1.234) increased the risk of HHD. Conclusions Graves disease, longer duration, old age, higher FT3 and TRAb are the risk factors of HHD. Timely prevention and control of risk factors is necessary to reduce the incidence of HHD.

Objective To compare the clinical significance of peripheral blood neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in predicting prognosis of patients with hepatocellular carcinoma (HCC).Methods The clinical data of 661 patients with HCC were retrospectively analyzed.Routine peripheral blood test results were used to calculate the NLR and PLR,and the receiver operating characteristic (ROC) curves were drawn.Using the thresholds of NLR and PLR,the patients were divided into the low NLR group and the high NLR group,and the low PLR group and the high PLR group.Overall survival (OS) and disease free survival (DFS) were evaluated by the Kaplan-Meier method.Independent prognostic predictors were determined by the Cox proportional hazard model.Results The NLR and PLR thresholds were 2.790 and 99,respectively.Analysis of the ROC curves showed higher NLR and PLR were significantly associated with poorer OS and DFS (all P ＜ 0.05).Multivariate analysis showed that NLR was an independent risk factor of OS and DFS (both P ＜ 0.05).The results remained unchanged when the NLR was further analyzed by applying different cut-off values of 2.810 and 3.In subgroup analysis,NLR remained an independent factor of Barcelona Clinical Liver Cancer staging system (BCLC) 0/A/B (P ＜ 0.05 for all measurements).Conclusion An elevated preoperative NLR could be a better prognostic predictor for HCC patients in comparison with PLR,especially for BCLC 0/A/B patients.

Objective To observe the effect of myocardial transcription factor MRTF-A on myocardium inflammation and its mechanism.Methods Totally 30 rats were randomly divided into the sham,ischemia-reperfusion (myocardial ischemia 30 min and reperfusion 2 h),and MRTF-A groups(myocardial ischemia 30 min and reperfusion 2 h & Lentivirus infection MRTF-A) (n=10 each group).Serum myocardial enzyme activity was detected by biochemical analysis,myocardial infarct size detected by TTC,and degree of myocardial injury was measured by HE staining.The TLR4 and TRIF expression was analyzed by immunohistochemistry and qPCR.Results Compared with the sham group,the MRTF-A group significantly increased the activity of serum myocardial enzymes CK-MB and LDH (P＜0.05).The infarct area of myocardial tissue was gray-white,and the infarct area was (54.31±3.07)％ (P ＜ 0.05).Myocardial fibrosis was disorder,myocardial cell was swollen and burst,and inflammatory cell infiltration was obvious.Protein and mRNA expressions of TRL4 and TRIF were significantly up-regulated (P＜0.05).Compared with the ischemia-reperfusion group,the levels of CK-MB and LDH were significantly reduced after myocardial infection with MRTF-A (P＜0.05).The myocardial infarction area was significantly reduced to (16.74±4.26)％ (P＜ 0.05).The myocardial structure was nearly normal with mild edema.Protein and mRNA expression of TRL4 and TRIF decreased significantly (P＜0.05).Conclusions The overexpression of transcription factor MRTF-A in myocardial cells alleviates the myocardial ischemia reperfusion injury by inhibiting the TLR4/TRIF signaling pathway and reducing the serum myocardial enzyme activity and myocardial damage.

OBJECTIVETo analyze the clinical outcome of 934 primary nasopharyngeal carcinoma treated with conventional external beam radiotherapy alone.

METHODS34 patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields were delineated according to the CT/MRI imaging findings on disease extent. Two lateral opposing isocentric portals with customized blockings were used for the nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68-70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7 weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients with negative lymph node.

RESULTSThe 1-, 2-, 3- and 4-year overall survival rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively. The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic course, the percentage of residual disease was 14.6%. The 4-year loco-regional recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2% with a median time of 19.3 months and 12.8 months.

CONCLUSIONIt may be helpful to improve radiotherapy curative effect when the target is individually designed through improving irradiation technique according to CT/MRI findings and by shortening the overall course time, enhancing irradiation dose and strictly implementing QA/QC measures.

Adolescent ; Adult ; Aged ; Carcinoma, Squamous Cell ; diagnostic imaging ; radiotherapy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnostic imaging ; radiotherapy ; Radiotherapy Dosage ; Retrospective Studies ; Survival Analysis ; Tomography, X-Ray Computed ; Treatment Outcome

OBJECTIVETo investigate the clinical features of unexpected sudden death (SUD) clustered in families in Yunnan province.

METHODSThis retrospective study analyzed the clinical features of SUD occurred between July to September 2005 in 7 families in Yunnan province.

RESULTSAll 16 SUD patients shared common clinical features such as fatigue and repeated syncope and one group of SUD patients (n = 8 from 4 families) presented with the gastric intestinal tract manifestations including nausea, vomiting, abdominal pain and diarrhea with suspected dietary history and abnormal laboratory enzyme findings (GOT/GPT, CK/CKMB, LDH/LDH1 etc.). In SUD patients without gastric intestinal tract manifestations (n = 8 from 3 families), there were no clear symptoms before death and repeated ventricular tachycardia and ventricular fibrillation were recorded in one survivor. There was no clear evidence for the involvements of hereditary and infectious factors for observed SUD.

CONCLUSIONThe reason for the unexpected sudden death clustered in 7 families in Yunnan remains unclear. Repeated syncope and fatigue served as the common clinical features in the presence or absence of gastric intestinal tract manifestations in all SUD cases. Further studies are needed to clarify the pathology and detailed clinical manifestations of SUD occurred in this area.

Adolescent ; Adult ; Bias ; Cause of Death ; Child ; China ; epidemiology ; Death, Sudden ; epidemiology ; Family ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVEThe purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province.

METHODThe electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women].

RESULTSThe incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern.

CONCLUSIONThe significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.

Adolescent ; Adult ; China ; epidemiology ; Death, Sudden ; epidemiology ; etiology ; Electrocardiography ; statistics & numerical data ; Female ; Humans ; Long QT Syndrome ; physiopathology ; Male ; Mass Screening ; Middle Aged ; Young Adult

In this study, Notopterygii Rhizoma et Radix was used to verify the stability and accuracy of DNA barcodes in identification of Chinese materia medica for the first time. All genomic DNAs from thirty one samples were extracted. The ITS (internal transcribed spacer) regions were amplified and sequenced bi-directionally. Obtained sequences were assembled using the CodonCode Aligner. And the sequences of the ITS regions were aligned through Clustal-W and the genetic distances were computed using MEGA 5.0 in accordance with the kimura 2-parameter (K2P) model. The neighbor-joining (NJ) phylogenetic trees were constructed. The ITS2 regions were obtained by using the hidden Markov model (HMM)-based annotation methods from the ITS sequences. Results indicated that the lengths of ITS regions of Notopterygii Rhizoma et Radix were 603-604 bp, while the lengths of ITS2 regions were 228 bp. The haplotypes of ITS/ITS2 regions of Notopterygii Rhizoma et Radix were the same as those of the original plant leaves. The intra-specific genetic distances were smaller than inter-specific ones in ITS/ITS2 regions of Notopterygium incisum and N. franchetii. The NJ trees showed that N. incisum, N. franchetii and its adulterants can be easily differentiated according to their monophyly. Therefore, ITS/ITS2 regions as DNA barcodes can stably and accurately distinguish Notopterygii Rhizoma et Radix from its adulterants and could provide a new technique to ensure clinical safety in utilization of traditional Chinese medicines.
Apiaceae ; classification ; genetics ; DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; genetics ; DNA, Ribosomal Spacer ; genetics ; Phylogeny ; Plant Roots ; genetics ; Plants, Medicinal ; genetics ; Rhizome ; genetics

OBJECTIVETo establish the tridimensional culture method for tissue-engineered skin to observe the histomorphological change in human immortal KC strain (HacaT)cocultured with xenogenic acellular dermal matrix (ADM).

METHODSThe ADM was prepared from SD rats by a modified method. HaCaTs were cultured in defined KC-serum free medium. HaCaTs in log growth phase were inoculated on ADM at the cell density of 2 x 10(5)/cm(2). They were submergedly cultured for 5 days and then changed to air-liquid phase culture for another 5 days. ADM and growth of HaCaTs on day 1 and 5 after cocultured with ADM were observed with scanning electron microscope. The histological change in ADM and HaCaTs on day 1, 5, and 10 after cocultured with ADM were examined by HE staining.

RESULTSThe gross appearance of ADM was white with smooth and soft texture, and intact collagen bundles without cellular residue. HaCaTs adhered and stretched out pseudopodia on the surface of the ADM on day 1 after combined culture, and a monolayer of cells was formed on day 5, growing into 3-6 layers of cells on day 10 with a tendency to grow into ADM.

CONCLUSIONSSD rats ADM is benefit for the adhesion of HaCaTs and the permeation of nutrient solution, from which an engineered multiple-layered human skin can be obtained within 10 days.

Animals ; Cells, Cultured ; Coculture Techniques ; Dermis ; cytology ; Humans ; Keratinocytes ; cytology ; Rats ; Rats, Sprague-Dawley ; Skin, Artificial ; Tissue Engineering ; methods

OBJECTIVE: To investigate the therapeutic effect of moxibustion on sarcomas from mesenchymal tissues, which have a low response rate to chemotherapy and radiotherapy. METHODS: S180 sarcoma cell line was inoculated in C57BL/6 mice to form transplanted tumor. Moxibustion therapy was directly applied at the transplanted tumor sites, at a distance of 3.0 cm, 10 min per session, till skin temperature reached 45 °C, once a day, for 14 consecutive days of intervention. After the mice were killed, serum was collected and used to detect concentrations of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), IL-4 and interferon-γ (IFN-γ) by Luminex liquid suspension chip. The numbers of Treg RESULTS: Weight of S180 transplanted tumor in the control group was (2.03 ± 0.54) g, and that in the moxibustion group was (1.27 ± 0.29) g, which was statistically different (P = 0.023). The mean value of Foxp3 CONCLUSION Moxibustion may have therapeutic effects on sarcomas by reducing the number of Treg cells in the blood and controlling the infiltration of Treg cells in the TME.