Hepatocellular carcinoma is one of the most common malignant tumors worldwide, posing a great threat to human health and life. Despite the tremendous progress in understanding the origin and molecular characterization of hepatocellular carcinoma, there are still few therapeutic options that can significantly increase the survival rate and improve the quality of life of patients. Protein post-translational modifications (PTMs) are regulatory mechanisms for protein activity, localization, expression, and interactions with other cellular molecules that induce changes in protein properties and functions. More and more studies have demonstrated that PTMs and immunotherapy play an important role in the development of hepatocellular carcinoma, even in the immunosurveillance of hepatocellular carcinoma and the treatment and prognosis of hepatocellular carcinoma patients. Traditional types of PTMs include phosphorylation, glycosylation, methylation, and ubiquitination. Phosphorylation affects cancer development and progression by regulating tumor cell proliferation, invasion and metastasis, and inhibiting apoptosis. There are two main types of glycosylation: O-glycosylation andN-glycosylation. Abnormal glycosylation not only promotes the proliferation and metastasis of hepatocellular carcinoma cells, but also plays an important role in immune recognition and immune escape. Common methylation modifications include DNA methylation, RNA methylation and histone methylation. Among them, histone methylation, as an important epigenetic regulatory mechanism, is of great theoretical and practical significance for understanding the mechanism of hepatocellular carcinoma as well as carrying out the corresponding prevention and immunotherapy. Ubiquitination plays an important role in the localization, metabolism, function, regulation and degradation of proteins, and it is regulated at different levels by ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin-conjugating enzyme (E3), and a series of deubiquitinating enzymes (DUBs) and is closely related to hepatocellular carcinoma immunotherapy. This paper begins with a brief overview of the importance of PTMs of proteins, discusses the importance of these traditional types of PTMs in hepatocellular carcinoma immunotherapy, and summarizes the most recent applications of these approaches in hepatocellular carcinoma in order to explore the mechanism of action of PTMs in hepatocellular carcinoma immunotherapy. Then, we summarize the finding that programmed death-ligand 1 (PD-L1) is associated with a variety of conventional types of PTMs, that in-depth study of the mechanisms regulating PD-L1 expression in tumor cells is expected to improve therapeutic efficacy, and that targeting PD-L1 in PTMs is expected to be a new field for exploring hepatocellular carcinoma immunotherapy in the future. Finally, we discuss the current status of research on PTMs for hepatocellular carcinoma immunotherapy and provide new insights and future research directions. In addition to the traditional types of PTMs, multiple novel PTMs have also been identified in published research reports, while the relationship between novel PTMs and hepatocellular carcinoma and the types of PTMs to other undiscovered proteins are still poorly understood, and future research will be focused on a more comprehensive knowledge and understanding of PTMs as well as on exploring new types and mechanisms of PTMs. Overall, further investigation of the role of PTMs in tumor immunity could help to discover new biomarkers and to develop more effective and personalized cancer immunotherapies and targeted therapies, expanding our understanding of cancer biology.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Behcet Syndrome ; Humans ; Thrombosis ; Vasculitis ; Venous Thrombosis ; Warfarin

Objective To investigate the expression of HERV-HLTR-associating protein 2(HHLA2).in hepatocellular carcinoma(HCC) tissue and its relationship with different pathological grades,clinical stages,liver function and serum AFP level.Methods The positive rate of HHLA2 expression in 150 cases of paraffin-embedded HCC tissues was detected by immunohistochemistry.Ten cases of normal liver tissue specimens from health donors served as the normal control.The differences of HHLA2 expression in HCC tissues were compared among different pathological grades,clinical stage,liver function grades and serum AFP levels.Results The positive expression rate of HHLA2 in HCC tissue was significantly higher than that in normal control (P＜0.05).The positive rate of HHLA2 expression in low differentiated HCC tissue was highest.The positive rate of HHLA2 expression in the low differentiation and moderate differentiation HCC groups was significantly higher than that in the high differentiation group (P＜0.05).The positive expression rate in the patients with Barcelona stage C and D was significantly higher than that in the patients with the stage A and B(P＜0.05).The positive expression rate in the patients with Child-Pugh stage A was significantly higher than that in the patients with stage B and C(P＜0.01).While the HHLA2 expression rate had no statistically significant difference among different ages and different serum AFP levels(P＞0.05).Conclusion The positive expression rate of HHLA2 in cancer tissues of HCC patients is significantly increased.HHLA2 might play a certain role in the occurrence,development and metastasis of HCC.

Objective: To observe the short- and long-term clinical outcomes of fraction flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients with SYNTAX score≥33 unsuitable for coronary artery bypass grafting (CABG). Methods: A total of 117 CAD patients admitted in our hospital from 2012-01 to 2015-06 were enrolled. Since SYNTAX score≥33, EuroSCORE>6, the patients were unsuitable for CABG and treated in 2 groups: Medication group, n=20 and PCI group, during FFR-guided PCI procedure, patients received ROTA or IVUS according to physician's experience, n=97. All patients were followed-up for at least 12 months. Meanwhile, taking "coronary stent and bypass", "CABG and PCI" as key words, we searched relevant documents in VIP Chinese science and technology journal full-text database, WanFang medical database, ChinaNet and Chinese biomedical literature database from 2012-01-01 to 2015-12-31, patients' outcomes were compared with the above references to explore the clinical benefit. Results: ① PCI group and Medication group had similar SYNTAX score and EuroSCORE, P>0.05. The common pathogenesis was LAD involvement, chronic occlusion was 31.3% (5/16) in patients with partial revascularization.②PCI group had 18.6% (18/97) incidence of major adverse cardiac and cerebral events (MACCE), 2 patients died during follow-up period and 9 received revascularization; Medication group had 60% (12/20) incidence of MACCE, 3 patients died during follow-up period; the difference between 2 groups showed statistical meaning, P<0.05.③There were 22 relevant documents retrieved as comparison; in our research, PCI group had similar incidence of MACCE to the documents, P>0.05; Medication group had increased incidence of MACCE than the documents, P<0.05. Conclusion: FFR-guided PCI could bring clinical benefit in CAD patients with SYNTAX score≥33 unsuitable for CABG.

There is increasing recognition of the importance of the quality of life (QOL) since it became an endpoint of clinical practices, a variety of disease-specific quality of life instruments have been developed and used as a means of assessing clinical interventions. Traditional evaluation was performed by researchers who generally ignore the subjective feeling from pa-tiens. At present, many evaluation criteria has paid more attention to the patient's subjective feelings into the scoring system, the assessment tool of patient-reported outcome (PRO) is usually the patient self-rating scale or questionnaire. As a common complica-tions of terminal stages of cancer, the treatment of bone metastases is usually conservative, improving or maintaining the quality of life of patients has been the consensus. Bone metastases trials have employed QLQ-C30 which raised by Europe Organization for Research and Treatment of Cancer (EORTC) or other generic health related QOL measurement, such as functional assessment of cancer therapy-general (FACT-G) and the MOS 36-item short from health survey (SF-36). But they lack specificity and accuracy in the assessment. EORTC QLQ-BM22 scale is considered as a bone metastases specific scale which was introducted in 2009, after the reliability, validity, cross-cultural adaptability verification, with the combination of EORTC QLQ-C 30 or used alone, has in-creasingly applied to clinical trials and practice for QOL assessment of bone metastatic cancer patients in recent years. It complete the EORTC evaluation system, which has significant value for assessing efficacy. EORTC QLQ-BM 22 has been translated into sim-plified Chinese and evaluated its utility, could be used in China as an effective questionnaire in evaluating the QOL for patients with bone metastases. In this study, current situation and progress of QOL measuring tools for bone metastases patients is re-viewed, in order to help researchers choose appropriate scale and better assess the efficacy, find the pros and cons to guide the clinical treatment decision.

BACKGROUNDPneumomediastinum (PM) secondary to foreign body aspiration (FBA) is rare in children. Although it is mainly benign, some cases may be fatal. Due to the rare nature of this clinical entity, proper assessment and management have been poorly studied so far. Here, we characterized the presentation and management of this clinical entity and provided an evaluation system for the management.

METHODSWe retrospectively reviewed children with PM secondary to FBA, who were treated in Beijing Children's Hospital from January 2010 to December 2015. All patients were stratified according to the degree of dyspnea on admission, and interventions were given accordingly. Bronchoscopic removals of airway foreign bodies (FBs) were performed on all patients. For patients in acute respiratory distress, emergent air evacuation and/or resuscitations were performed first. Admission data, interventions, and clinical outcomes were recorded.

RESULTSA total of 39 patients were included in this study. The clinical severity was divided into three grades (Grades I, II, and III) according to the degree of dyspnea. Thirty-one patients were in Grade I dyspnea, and they simply underwent bronchoscopic FBs removals. PM resolved spontaneously and all patients recovered uneventfully. Six patients were in Grade II dyspnea, and emergent drainage preceded rigid bronchoscopy. They all recovered uneventfully under close observation. Two exhausted patients were in Grade III dyspnea. They died from large PM and bilateral pneumothorax, respectively, despite of aggressive interventions in our hospital.

CONCLUSIONSPM secondary to FBA could be life-threatening in some patients. The degree of dyspnea should be evaluated immediately, and patients in different dyspnea should be treated accordingly. For patients in Grade I dyspnea, simple bronchoscopic FBs removals could promise a good outcome. For patients in Grade II dyspnea, emergent air evacuation and/or resuscitation should precede a bronchoscopy before the children become exhausted.

Child, Preschool ; Female ; Foreign Bodies ; complications ; Humans ; Infant ; Male ; Mediastinal Emphysema ; diagnosis ; Pneumothorax ; diagnosis ; Retrospective Studies ; Subcutaneous Emphysema ; diagnosis

Objective To compare the relationship between the enzyme‐linked immunosorbent assay(ELISA) reagent and West‐ern blot(WB) confirmation reagent for analyzing the quality lever of human T‐cell lymphotropic virus(HTLV) detection reagent . Methods The WB confirmation reagent was used to detect anti‐HTLV antibody in 156 human serum samples of ELISA prelimina‐ry screening positive .The ELISA cut‐off value(optimal value) was selected by using the two‐graph receiver operating characteristics (TG‐ROC) analytical method .The two‐by‐two table analysis was constructed to analyze the consistency of results detected by the two methods ,moreover the McNemar test was used to evaluate the consistency of detection results .The quality level of HTLV de‐tection reagent was comprehensively evaluated .Results Among 156 serum samples of ELISA preliminary screening positive ,only 40 samples were positive by the WB confirmation ,and other 116 samples were negative .The sensitivity and specificity of ELISA de‐tection reagent obtained by TG‐ROC analysis were 97 .5% and 45 .7% respectively ,the TG‐ROC test also indicated that the detec‐tion results had significant difference between ELISA and WB(P<0 .05) .By adjusting the cut‐off value ,the sensitivity and specific‐ity of ELISA were increased to 88 .8% (parametric method) .In the comparison of the parametric method and the non‐parametric method ,the obtained areas under the curve(AUC) was 0 .923 5(parametric method) ,their results were basically consistent .Conclu‐sion Although above results indicate that the detection results of ELISA reagent are different from those of WB ,but adjusting the cut off value can increase its sensitivity and specificity ,thus increases the reliability of diagnosis result .

With an objective to provide an experimental basis for scientific officinal of Schisandrae Sphenantherae Fructus, this research uses UPLC-TQ/MS method to analyze 7 different kinds of lignan in 70 batches of Schisandra sphenantherae Fructus samples from 9 regions. The results showed that in the area south of Qinling mountains, Schisandrae sphenantherae Fructus from Zhashui county and Shanyang county of Shangluo mainly contained schisantherin A and deoxyschizandrin. However, Schisandrae sphenantherae Fructus from Mei county of Baoji, Shiquan county and Ningshan county of Ankang, and Lueyang county of Hanzhong, mainly contained anwuligan. Samples from Ningshan county also consists relatively high level of deoxyschizandrin. In the central area of Qinling mountains and the Daba mountains, Schisandrae Sphenantherae Fructus from Nanzheng county of Hanzhong mainly contained schisanhenol and deoxyschizandrin. In conclusion, the kinds and level of lignan differ significantly in Schisandrae sphenantherae Fructus produced in different regions. In practical application, Schisandrae Sphenantherae Fructus produced in different regions should be distinguished and differently applied based on their main effective components corresponding to different diseases, which can lead to the best clinical use.
China ; Drugs, Chinese Herbal ; chemistry ; Fruit ; chemistry ; Lignans ; chemistry ; Quality Control ; Schisandra ; chemistry

OBJECTIVETo establish a surgical classification system for metastases of proximal femur and discuss the therapeutic strategy with retrospective analysis and literature review.

METHODSThe data of 99 patients who underwent a total of 102 operations for femoral metastatic lesions from January 2003 to December 2011 was analyzed. There were 50 males and 49 females, and the median age was 56 years (range 15-87 years). The most common diagnosis was lung cancer (30 cases), followed by breast cancer (17 cases). All femoral lesions were divided into 4 types (I-IV) with different anatomic site and biomechanic characteristic. The patients with various surgical reconstruction mode and postoperative follow-up data were recorded.

RESULTThere were 65 side who received widely or marginal resection and 37 side who received intralesional resection. The patients were operated with bipolar hip prosthesis (n = 3), ordinary total hip replacement (THR) (n = 10), bipolar tumor prosthesis (n = 48), THR with tumor prosthesis (n = 8), intramedullary nailing (n = 21), and plate/screw (n = 12). The estimated survival for the 99 patients was 10.3 months. Type I, II, III and IV patients with postoperative American Society of bone and soft tissue tumors-93 rating were 86.5%, 77.3%, 81.3% and 69.1%. Patients with type IV were worse compared with the other 3 groups (t = 4.763, P = 0.031). The 10 operations were followed by complications of any kind. Complication rate of patients with type IV were 3/12, and it was significantly higher than the other 3 groups of patients (χ(2) = 4.018, P = 0.045).

CONCLUSIONSThe classifications and corresponsive surgical methods for upper femur metastases had some superiority in hinting prognosis and guiding treatment.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; Female ; Femoral Neoplasms ; classification ; secondary ; surgery ; Femur ; surgery ; Fracture Fixation, Intramedullary ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult