Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.

ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.

Humans ; Pulmonary Disease, Chronic Obstructive ; Smoke/adverse effects* ; Tobacco ; Tobacco Smoke Pollution

Objective To study the effects of integrated orthopedic rehabilitation pathway on motor function in six months after total knee arthroplasty (TKA), including pain, stiffness, range of motion and muscle strength, etc. Methods From March, 2016 to March, 2019, 180 patients who underwent TKA and treated with integrated orthopedic rehabilitation pathway were enrolled. Age, gender, operation time, time of follow-up, the scores of Hospital for Special Surgery-Knee Scale (HSS-KS) and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) at preoperative/postoperative/one-month after operation/three-month after operation/six-month after operation time points were collected. The sub items, such as muscle strength, range of motion, flexion deformity, pain, stiffness, functional difficulty were primarily focused on. Results A total of 42 patients were followed up for three months and 22 patients were followed up for six months. There was no significant difference in the scores of HSS-KS and WOMAC before and after operation (P > 0.05). Within three months after operation, the HSS-KS scores gradually increased (P < 0.05) and the WOMAC scores gradually decreased (P < 0.05). The active knee flexion range of motion and knee extensor muscle strength scores of HSS-KS significantly decreased after operation (P < 0.05), and gradually recovered one month and three months after operation (P < 0.05). The flexion deformity scores of HSS-KS increased after operation (P < 0.05), decreased one month after operation (P < 0.05), and got a trend of incensement again three months after operation. The pain score of WOMAC decreased continuously within three months after operation (P < 0.05); the stiffness score of WOMAC did not change after operation (P > 0.05), decreased significantly one month after operation (P < 0.05), and did not change three months after operation (P > 0.05). The degree of functional difficulty of WOMAC decreased after operation (P < 0.05), and improved continuously within six months after operation (P < 0.05). Conclusion The overall function after TKA shows a trend of improvement within three months, and there is no obvious improvement from three to six months after operation. The flexion deformity score showed a downward trend in one month after operation, and it could be improved again after strengthening rehabilitation, which needs more attention in the postoperative rehabilitation.

Objective:To evaluate the effect of general anesthesia under the guidance of bispectral index (BIS) on postoperative fatigue syndrome (POFS) in elderly patients undergoing laparoscopic resection of gastrointestinal tumor.Methods:A total of 90 patients of both sexes, aged 65-80 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiology physical status Ⅰ-Ⅲ, undergoing elective laparoscopic resection of gastrointestinal tumor, were divided into 3 groups ( n=30 each) using a random number table method: control group (C group), BIS value 40-49 group (B1 group), and BIS value 50-60 group (B2 group). Combined intravenous-inhalational anesthesia was used.The intraoperative BIS value was maintained at 40-49 in group B1, the intraoperative BIS value was maintained at 50-60 in group B2, and the fluctuation range of heart rate and mean arterial pressure was maintained within 20% of the baseline value during operation, and vasoactive drugs were given when necessary in group C. Patient-controlled intravenous analgesia was performed with sufentanil plus dezocine plus palonosetron after surgery, when the VAS score > 3 points, oxycodone/acetaminophen tablets 5 mg were administered orally or flurbiprofen axetil 50 mg was intravenously injected for rescue analgesia.The Christensen′s Fatigue Scale (CFS) scores were recorded at 1 day before operation and 1, 3, 7 and 30 days after operation, and the development of POFS (CFS score ≥ 6) was recorded.The intraoperative consumption of propofol, remifentanil and sufentanil was recorded.The serum C-reactive protein concentration was determined by immunoturbidimetry at 1 day before operation and 1 day after operation.The requirement for rescue analgesia within 48 h after operation was recorded.The time to the first flatus, the first ambulation time, length of hospital stay, and occurrence of fever, vomiting and delirium within 3 days after operation were recorded.The Quality of Recovery-15 (QoR-15) scores were measured at 1, 3 and 7 days after operation. Results:Compared with group C, CFS scores were significantly decreased at 1, 3 and 7 days after surgery, the incidence of POFS was decreased at 7 days after surgery, QoR-15 scores were increased at each time point after operation, the length of hospital stay was shortened, and the intraoperative consumption of propofol was reduced in B1 and B2 groups ( P<0.05). Compared with group B1, the intraoperative consumption of propofol was significantly reduced, QoR-15 scores were increased at each time point after operation ( P<0.05), and no significant change was found in CFS scores, incidence of POFS at each time point after operation, or length of hospital stay in group B2 ( P>0.05). There were no significant differences in serum C-reactive protein concentration, postoperative requirement for rescue analgesia, time to first flatus, first ambulation time, and incidence of fever, vomiting and delirium at each time point among the three groups ( P>0.05). Conclusions:General anesthesia under BIS guidance can reduce POFS and promote early postoperative recovery in elderly patients undergoing laparoscopic resection of gastrointestinal tumor.

Objective:To integrate qualitative research on the experience of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) , to understand the experience of patients with pulmonary rehabilitation and its influencing factors, so as to provide evidence support for pulmonary rehabilitation.Methods:Qualitative research on pulmonary rehabilitation experience of COPD patients was retrieved by computer in 8 databases including the Cochrane Library, Web of Science, Embase, PubMed, CINAHL, China National Knowledge Infrastructure, WanFang and VIP. The retrieval time limit was from the establishment of the database to August 20, 2021. The quality of the articles those met the requirements were evaluated by the quality evaluation criteria for qualitative research of the Australian Joanna Briggs Institute Evidence-Based Health Care Center, and the results of each study were further integrated and analyzed.Results:A total of 12 articles were included, and 47 clear topics were extracted, and similar topics were summarized into 7 new categories. A total of 3 integrated results were synthesized, namely rehabilitation efficacy, pulmonary rehabilitation motivation, and pulmonary rehabilitation obstacles.Conclusions:COPD patients who can persist in training perceive the benefits of pulmonary rehabilitation, and both the pulmonary rehabilitation environment and interpersonal support are factors that promote their pulmonary rehabilitation. The patients' own condition and transportation and economic difficulties are the main obstacles. Therefore, the patients' physical and economic status should be comprehensively evaluated during pulmonary rehabilitation, and the most suitable pulmonary rehabilitation program should be selected.

Objective:To investigate the role of p21 gene in the radiation-induced heart disease (RIHD) and to evaluate the effect on p21 gene knockout on RIHD phenotype in mouse models.Methods:p21 -/-mice were utilized in the experimental group, and p21 + /-mice were allocated in the control group. RIHD mouse models were established by exposure to 10 Gy whole heart irradiation by using a small animal radiation research platform. The heart samples were collected at 6 weeks after irradiation, the gross specimens were measured and subject to HE staining. The wall thickness and left ventricular ejection fraction of the mice were detected by the Vevo2100 ultrasound imaging system. The hypoxia in cardiac tissues was detected by the hypoxia probe method. The apoptosis of cardiac cells was determined by Tunel method. Results:Compared with the p21 + /-mice, the survival of p21 -/-mice was significantly shortened ( P=0.004), the interventricular septum was significantly thinned during the diastolic and systolic phases ( P=0.049, P=0.006), the left ventricular posterior wall was remarkably thickened ( P<0.001) and the left ventricular ejection fraction was significantly decreased ( P=0.004). The gross heart tissue was enlarged in the p21 -/-mice. HE staining showed the aggregation of inflammatory cells in cardiac tissues and disordered arrangement of myocardial cells. Significant hypoxia and apoptosis could be observed in the p21 -/-mouse heart tissues. Conclusions:p21 -/-mice are prone to more severe RIHD after irradiation, manifested with shortened cardiac survival, weakened cardiac function, abnormal cardiac structure, hypoxia and apoptosis of cardiac tissues. p21 plays an important role in the repair after cardiac irradiation.

Objective:To evaluate the effect of general anesthesia guided by bispectral index (BIS) on postoperative sleep quality in elderly patients undergoing laparoscopic gastrointestinal tumor surgery.Methods:A total of 90 patients, aged 65-80 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiology physical status Ⅰ-Ⅲ, without preoperative sleep disorders, undergoing elective laparoscopic gastrointestinal tumor surgery, were divided into 3 groups ( n=30 each) using a random number table method: control group (group C) and different BIS value groups (group B1 and group B2). Combined intravenous-inhalational anesthesia was used.The BIS value in group B1 was maintained at 40-49, and the BIS value in group B2 was maintained at 50-60.The fluctuation range of heart rate and blood pressure was not more than 20% of the baseline, and vasoactive agents were administered when necessary in group C. Patient-controlled intravenous analgesia was performed with sufentanil, dezocine and palonosetron after surgery.When visual analog scale score>3, acetaminophen oxycodone tablets 5 mg was taken orally or flurbiprofen 50 mg was intravenously injected as rescue analgesic.At 1 day before surgery and 1, 3, 7 and 30 days after surgery, sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), postoperative sleep disorders were defined as PSQI scone≥6, and the development of postoperative sleep disorders was recorded.During the nighttime at 1 day before surgery and during the nighttime at 1, 2 and 3 days after surgery, sleep was monitored using body motion monitor (Honor Band 5). The intraoperative consumption of propofol and remifentanil and requirement for rescue analgesia at 48 h after surgery were recorded.The Quality of Recovery-15 (QoR-15) scores were measured at 1, 3 and 7 days after surgery.At 1 day before surgery and at 1 day after surgery, serum C-reactive protein concentrations were determined by immunoturbidimetry. Results:Compared with group C, PSQI scores were significantly decreased at 1 and 3 days after surgery, the incidence of sleep disorders was decreased at 3 days after surgery, sleep time, sleep score and proportion of rapid eye movement sleep time during the nighttime at 1 and 2 days after surgery were increased, intraoperative consumption of propofol was decreased, QoR-15 score at each time point after surgery was increased, and postoperative length of hospital stay was prolonged in group B2 and group B2 ( P<0.05). Compared with group B1, PSQI scores were significantly decreased at 1 and 3 days after surgery, sleep time, sleep score and proportion of rapid eye movement sleep time during the nighttime at 1 and 2 days after surgery were increased, intraoperative consumption of propofol was decreased, QoR-15 score at each time point after surgery was increased ( P<0.05), and no significant change was found in the incidence of sleep disorders at each time point in group B2 ( P>0.05). There was no significant difference in CPR concentrations and the number of rescue analgesia after surgery at each time point among the 3 groups ( P>0.05). Conclusion:General anesthesia guided by BIS can improve postoperative sleep quality in elderly patients undergoing laparoscopic gastrointestinal tumor surgery, and BIS value maintained at 50-60 provides better effect on postoperative sleep quality and is more helpful for postoperative recovery.

Objective:To compare the application of 13N-NH 3, 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in the diagnosis and evaluation of suspected cerebral glioma. Methods:From September 2010 to December 2017, ninety patients (54 males, 36 females; age: (40.0±14.0) years) in the First Affiliated Hospital of Sun Yat-sen University with suspected glioma based on clinical diagnosis, who underwent 13N-NH 3, 11C-MET and 18F-FDG PET/CT imaging, were prospectively enrolled in the study. All patients were confirmed by histology or clinical and radiological follow-up. Images were interpreted by visual evaluation (higher radioactive uptake in lesions than that in the contralateral normal brain parenchyma was considered as positive (+ ), equal/lower were considered as negative (-)) and semi-quantitative analysis (the maximum standardized uptake value (SUV) of lesion (L) to the mean SUV of normal white matter (WM) (L/WM ratio)). Receiver operating characteristic (ROC) curve analysis was used and the area under curves (AUCs) were calculated and compared. The diagnostic efficacies of 3 imaging methods and the combination for diagnosing gliomas and the abilities to differentiating high-grade gliomas (HGG) and low-grade gliomas (LGG) were compared. Results:In 90 patients, 30 HGG, 27 LGG, 10 non-glioma brain tumors and 23 non-neoplastic lesions (NNL) were diagnosed. On visual evaluation, the sensitivities for differentiating tumors from NNL were 62.7%(42/67), 94.0%(63/67) and 35.8% (24/67) for 13N-NH 3, 11C-MET and 18F-FDG PET/CT respectively, while the specificities were 95.7%(22/23), 56.5% (13/23) and 65.2% (15/23), and the accuracies were 71.1%(64/90), 84.4%(76/90) and 43.3% (39/90). Taking the metabolic patterns of + /+ /+ , + /+ /- and + /-/- ( 11C-MET/ 13N-NH 3/ 18F-FDG) as the diagnosis standard of tumor lesions, the specificity and accuracy of the combined method increased to 73.9%(17/23) and 88.9%(80/90) with the sensitivity remaining the same (94.0%, 63/67). ROC curve analysis (L/WM) showed that the sensitivity, specificity and AUC were 64.2%(43/67), 100%(23/23) and 0.819 for 13N-NH 3 PET/CT, and 89.6%(60/67), 69.6%(16/23) and 0.840 for 11C-MET PET/CT ( z=-0.316, P>0.05). The accuracy for differentiating high and low grade glioma were 86.0% (49/57), 87.7%(50/57) and 93.0%(53/57) for 13N-NH 3, 11C-MET and 18F-FDG PET/CT, with the AUC of 0.896, 0.928 and 0.964, respectively ( z values: -0.554 to 1.334, all P>0.05). Conclusions:13N-NH 3 PET/CT imaging has remarkably high specificity but low sensitivity for the differentiation of brain tumors from NNL. 11C-MET PET/CT imaging was found to be highly useful for detection of brain tumors. However, like 18F-FDG, high MET uptake is frequently observed in some NNL. 13N-NH 3, 11C-MET and 18F-FDG PET/CT imaging all appear to be valuable for evaluating the histological grade of gliomas, and the combination of them is more useful for the accurate diagnosis of glioma.

Objective:To investigate the living status and quality of life (QOL) in type1 Gaucher disease (GD1) patients who underwent long-term enzyme replacement therapy (ERT) and identify possible relevant factors affecting QOL.Methods:Clinical data and SF-36 questionnaires were recorded in 22 adult GD1 patients under regular ERT at Peking Union Medical Colleague Hospital (PUMCH) from January 1995 to June 2017.Results:13 males and 9 females were included in this study. The current median age, age at diagnosis and initial time of ERT were 41 (24-52) , 6 (1-38) and 26 (6-41) years respectively. Of these patients, 68.2% was living in less-developed regions, 86.4% were under college education, and 77.3% had personal annual income less than ￥30 000 RMB. Though after a median 16 (7-22) years of ERT, the QOL of GD1 patients was still significantly worse ( P<0.05) compared with normal Chinese population based on SF-36 questionnaires. History of splenectomy was a negative factor of QOL, mainly in physical health ( P<0.05) . Patients could get benefit from early start of ERT in both physical and mental health ( P<0.05) . Mental health was not affected by history of splenectomy and related bone diseases. Conclusion:Most adult GD1 patients at PUMCH reside in less-developed regions and have low levels of education and annual income. History of splenectomy and time to start ERT are two important factors affecting QOL. Chinese adult GD1 patients are associated with reduced QOL, even after long-term ERT.