Volume 101 ·  Issue 48 ·  2021

With the development of ELISA, flow cytometry, quantitative PCR and various omics techniques, the means of immune function evaluation are gradually improved. The existing definitions of immune function, such as excessive immunity, immunosuppression, immune paralysis and immune tolerance, remain in descriptive concepts and lacks quantitative diagnostic criteria. Clinical manifestations combined with biological indicators will be the most effective quantitative method in the future. A variety of research concentrating on immunotherapeutic drugs is still in progress, and the success of individualized immunotherapy will depend on accurate immune function evaluation.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most patients are in the middle and late stage at the initial diagnosis, and systemic therapy is their main treatment method. In recent years, immune checkpoint inhibitors (ICI) have made breakthroughs in the systemic treatment of intermediate and advanced HCC, breaking the single therapeutic landscape of molecular targeted drugs. In order to better guide the rational, effective and safe application of immunotherapy drugs in clinical practice, the Liver Cancer Committee of Chinese Medical Doctors Association organized experts in relevant fields to form the following consensus on HCC immunotherapy based on clinical research and clinical medication experience, after many discussions and revisions, for reference by domestic peers.

To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality.

Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (allP<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d,P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (allP<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (allP<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD.

Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

To investigate the related factors of thrombosis in patients with non-valvular atrial fibrillation (NVAF), and whether the combination of D-dimer, left atrial anteroposterior diameter and CHA₂DS₂-VASc score can be used to exclude left atrial thrombosis.

A total of 75 NVAF patients with left atrial thrombosis confirmed by transesophageal echocardiography in Peking University People′s Hospital from January 1, 2015 to December 31, 2019 were enrolled as the thrombus group. From January 1 to October 31, 2019, 80 patients with NVAF without left atrial thrombosis were enrolled as the control group. The clinical data, CHA₂DS₂-VASc score, hematological biomarkers, ultrasound data of two groups were compared. The independent factors associated with left atrial thrombosis were screened by univariate analysis and multivariate logistic regression analysis. The positive predictive value and negative predictive value for the diagnosis of left atrial thrombosis were gained by the score calculated based on the independent related factors.

There were no significant differences in age, gender, proportion of persistent atrial fibrillation and duration of atrial fibrillation between the two groups. The CHA₂DS₂-VASc score [M (Q₁, Q₃)] of the thrombus group was higher than that of the control group [2.5 (1.0, 3.0) vs 1.8 (1.0, 3.0), P=0.012]. The prothrombin time activity [M (Q₁, Q₃)] of the thrombus group was 81.1 (72.0, 93.0)%, which was lower than that of the control group 88.8 (83.0,96.0)% (P=0.008). The activated partial thromboplastin time (APTT) of the thrombus group was longer than that of the control group [(32.1±4.8) s vs (30.2±3.7) s, P=0.006]. D-dimer [M (Q₁, Q₃)] of the thrombus group was 231.0 (71.5, 272.2) ng/ml, which was higher than that of the control group 121.7 (49.0, 140.0) ng/ml (P<0.001). The left atrial anteroposterior diameter in thrombus group was larger [(44.6±6.6) mm vs (38.9±5.3) mm,P<0.001], the proportion of mitral regurgitation was higher (58.1% vs 26.8%,P<0.001). The left ventricular ejection fraction [M (Q₁, Q₃)] of the thrombus group was 56.7% (45.8%, 66.3%), which was lower than that of the control group 63.3% (60.5%, 70.2%) (P=0.003). Multivariate logistic regression analysis showed that the factor related to left atrial thrombosis was left atrial anteroposterior diameter (OR=4.480, 95%CI: 1.616-12.423). The negative predictive value of the new scoring system combined with D-dimer, left atrial anteroposterior diameter and CHA₂DS₂-VASc score for left atrial thrombosis was 100%.

In NVAF patients, the factor independently associating with left atrial thrombosis is left atrial anteroposterior diameter. The combination of D-dimer, left atrial anteroposterior diameter, and CHA₂DS₂-VASc score can help exclude left atrial thrombosis before ablation of NVAF.

To investigate the role of ubiquitin-specific peptidase 22 (USP22) in colorectal cancer multidrug resistance and its correlation with multidrug resistance genes P-gp and MRP1, and to preliminarily explore the mechanism of USP22 affecting colorectal cancer resistance.

USP22 over-expression plasmid was transfected into colorectal cancer cells (RKO, SW480)with low expression of USP22. Cell counting kit (CCK-8) assay was used to detect the effect of USP22 on oxaliplatin resistance in colorectal cancer cells. The cells were treated with oxaliplatin of the same concentration. Western blot method was used to detect the expression of apoptosis-related proteins cleaved-caspase3, Bcl-2, and drug resistance proteins MRP1, P-gp in the cells. The cell efflux test was used to detect the effect of up-regulated USP22 on Calcein-AM and rhodamine123. Immunohistochemical methods were used to detect the expressions of USP22 and P-gp in the oxaliplatin chemotherapy-sensitive group and the drug-resistant group and to analyze the correlation between USP22 and MRP1, P-gp.

CCK-8 assay showed that the IC₅₀ values of SW480-USP22 (SW480 cells overexpressing USP22) treated with oxaliplatin for 24 h and 48 h was (4.62±0.05)μmol/L and (2.32±0.04)μmol/L respectively; which was 2.7 times and 3.0 times higher than that in control cells, respectively. After treating with 1.25 μmol/L oxaliplatin for 48 h, USP22 overexpression can inhibit SW480 cells apoptosis. The fluorescence intensity of calcein-AM and rhodamine123 in the SW480-USP22 group were significantly increased when compared with that in the control cells (both P<0.01). The protein expression levels of MRP1 and P-gp in SW480-USP22 cells were significantly increased when compared with that in the control cells(bothP<0.01). Immunohistochemistry showed that the positive expression rates of USP22, MRP1, and P-gp in the oxaliplatin chemotherapy-sensitive group were significantly lower than those in the chemotherapy-resistant group, the difference was statistically significant (allP<0.05), and USP22 was positively correlated with the expressions of MRP1 and P-gp in colorectal cancer tissues (r₁=0.377, r₂=0.423, both P<0.05).

The up-regulation of USP22 is related to the acquired resistance of colorectal cancer cells to oxaliplatin. USP22 may be involved in the process of platinum-based chemotherapy resistance of colorectal cancer by regulating the expressions of P-gp and MRP1.

To analyze the effect of chronic kidney disease (CKD) on the long-term prognosis of patients with left main coronary artery disease after revascularization.

A total of 1 040 patients with lesions in unprotected left main coronary artery who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between January 2003 and July 2009 in Beijing An Zhen Hospital were enrolled (CKD group, n=240; non CKD group, n=800). The mean ages of CKD group and non CKD group were (68.9±6.5) and (61.1±9.7) years old, respectively. Patients were followed up through interviewing in clinic visit or calling by telephone. The primary endpoints of the study included death, myocardial infarction (MI) and stroke. Cox regression was used to analyze the associated factors on patients′ long-term prognosis.

The median follow-up for included 1 040 patients was 6.1 years (first quartile Q₁, 5.1 years; Q₃, 8.0 years). The total occurrence of death, MI and stroke in the CKD group (48.9%, n=96) was significantly higher than that in the non CKD group (30.7%, n=136) (P<0.001). In the CKD group, the total occurrence of the death, MI and stroke was 51.2% in patients with PCI (n=46) compared to that of 47.2% in patients with CABG (n=50). In the non CKD group, the total occurrence of death, MI and stroke was 17.7% and 36.7% in patients with PCI (n=45) and CABG (n=91), respectively. Cox proportional hazards regression model analysis showed that after adjusted for confounding factors, the risk of all-cause death/MI/stroke [HR (95%CI): 1.97 (1.49-2.62)], all-cause death [2.67 (1.89-3.78)], cardiac death [3.46 (2.25-5.33)] and MI [2.31 (1.41-3.80)] increased in patients with CKD after revascularization.

CKD significantly increases the occurrence of composite of death/MI/stroke, all-cause mortality, cardiac death and MI in patients with left main coronary artery disease after revascularization. There was no significant difference in the occurrence of the composite of death, MI and stroke between patients with PCI and those with CABG, regardless of in CKD group or non CKD group.

To analyze the early outcome of one-stage hybrid technique in the treatment of Stanford type-A aortic dissection involving the arch and compare its therapeutic efficacy with the classical frozen elephant trunk technique (FET).

A total of 106 patients with Stanford type-A aortic dissection involving the arch in Department of Cardiac and Vascular Surgery, 1st Affiliated Hospital of Soochow University from October 2015 to October 2019 was collected. All patients in this group were treated with one-stage hybrid technique (modified arch debranching technique) without deep hypothermia circulation. Meanwhile, 30 patients with Stanford type A dissection involving the arch who underwent FET from January 2014 to September 2015 were collected. The therapeutic effects of the two surgical methods were analyzed and compared.

The age [M (Q₁, Q₃)] of 106 patients in hybrid group was 49.0 (40.0, 55.0) years, including 89 males and 17 females. The age [M(Q₁, Q₃)] of 30 patients in FET group was 49.5 (41.5, 65.3) years, including 24 males and 6 females. The time [M(Q₁, Q₃)] of using ventilator in hybrid group was 56.0 (38.0, 72.0) h, which was shorter than 127.0 (92.0, 145.0) h in FET group (P<0.001). The incidence of cerebral infarction in hybrid group was 2.8% (3 cases), which was lower than 13.3% (4 cases) in FET group (P=0.042); the incidence of postoperative renal insufficiency in hybrid group was 7.5% (8 cases), which was lower than 23.3% (7 cases) in FET group (P=0.023); the ICU time [M (Q₁, Q₃)] in hybrid group was 8.0 (6.0, 10.0) d, which was shorter than 14.0 (8.3, 24.0) d in FET group (P<0.001).

Compared with FET, one-stage hybrid technology is safer and more effective in the treatment of Stanford type A aortic dissection involving the arch. Its short-term therapeutic efficacy appears good.

To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b.

From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery.

Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m². The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),bothP<0.05].

Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

To explore the accuracy and efficiency of a novel 3D-printed emulation localization model of small pulmonary nodules in lung surgery.

From April 2020 to April 2021, a total of 66 patients were selected in the study, who underwent localization and resection of pulmonary nodules with video-assisted thoracoscopic surgery (VATS) guided by the 3D-printed emulation localization model at Department of Thoracic Surgery, West China Hospital of Sichuan University. There were 13 males and 53 females, aged from 25 to 79 (52.7±11.4) years. Of all patients, 24 (36.4%) had single pulmonary nodule, and 42 (63.6%) had synchronous multiple pulmonary nodules. The chest high-resolution CT image data were utilized for digital reconstruction and 3D printing to make a tailored life-size emulation pulmonary nodules localization model, which was used to navigate real-time intraoperative localization of nodules. Clinical data including operative parameters, localization information, resection types and pathological findings of nodules were analyzed. The pulmonary nodules that doctors planned to resect were categorized into two categories:major nodules and additional nodules, according to their presence of invasion and radiological risk factors. The accuracy of localization and resection efficiency of nodules were evaluated in accordance with the categories of the nodules respectively.

On the basis of preoperative evaluation, there were 71 major nodules with median maximal diameter of 0.9 (0.6-1.3) cm, and 77 additional nodules with median maximal diameter of 0.5 (0.4-0.7) cm. All patients underwent VATS surgery, 52 of them (78.8%) were treated with uniportal VATS and 14 (21.2%) with triportal VATS. Among the patients with single nodule, 18 segmentectomies and 6 wedge resections were performed; whereas among the patients with multiple nodules, 5 segmentectomies, 14 wedge resections, and 23 combined pulmonary resections (including 2 cases of lobectomy+segmentectomy, 7 cases of lobectomy+wedge resections, and 14 cases of segmentectomy+wedge resections) were achieved. The median operative time was 93 (45-240) min, and the median resection time for all nodules was 51.4 (6.7-147.0) min. All major nodules were successfully resected and visibly dissected after removal, and all additional nodules were successfully resected with 85.7%(66/77) nodules visibly dissected. The accuracy rate of localization of both types of nodules was 100%. All major nodules were malignant, and the malignancy rate of additional nodules was 21.2%(14/66).

This novel 3D-printed emulation localization model of small pulmonary nodules proved to be a non-invasive, accurate and efficient technique. Not only that, it has a unique advantage in localization of synchronous multiple pulmonary nodules.

A pedigree genetic analysis of a female Duchenne muscular dystrophy (DMD) inherited from paternal chimerism was conducted to explore the genetic diagnosis strategy. No large deletions/duplications was found in the DMD gene of the proband. Next-generation sequencing (NGS) results showed that the proband had a heterozygous mutation in the DMD gene c.4707C>A (p.C1569X). This locus has not been reported in the literature and is considered as a pathogenic mutation. Sanger sequencing revealed that the father of the proband carried the same mutation, and the mosaic ratio was about 17.7%. The specific enzyme digestion test showed that the proband had maternal skewed X-inactivation. DMD a recessive inherited disease of the X chromosome, exists in female patients, and very few of them are inherited from paternal origin. Female patients need to pay close attention to skewed X-inactivation and suspected new mutations. Mosaic is not excluded, especially the inheritance of paternal mosaicism with normal phenotype. Prenatal gene screening is necessary for reproduction.

Mediastinal pancreatogenic pseudocyst is rare, its clinical manifestations are not specific, and it is easy to be misdiagnosed or misdiagnosed. A patient with dysphagia, pleural effusion accompanied by fever and hemoptysis, who was suspected of mediastinal cyst infection after diagnosis, was suspected of mediastinal pancreatic pseudocyst due to his history of alcoholism and imaging characteristics. Finally, the diagnosis was confirmed by endoscopic ultrasound puncture, which found that the level of pancreatic enzymes in cystic fluid was significantly increased. Disappearance of mediastinal pseudocyst after endoscopic retrograde cholangiopancreatography with pancreatic duct stent drainage.

With the official inclusion of rubella vaccine in the expanded immunization program in China in 2008, the immunization coverage rate of infants and young children has remained above 95% since 2012. Therefore, a certain immune barrier has been established among the population, which makes the incidence of rubella in China decrease year by year, and gradually blocks the spread of local epidemic rubella virus, indicating that China is moving towards the goal of rubella elimination. However, in order to accelerate the process of rubella elimination in China, supplementary immunization strategies for key populations should be scientifically formulated according to the monitoring situation, and the ability to deal with outbreaks should be improved. At the same time, it is necessary to build a medical and prevention integration mechanism and promote the monitoring of congenital rubella syndrome, so as to provide evidence support for rubella elimination.

Urinary stones are common extraintestinal manifestations in patients with inflammatory bowel disease. Because of their high incidence and serious complications such as recurrent urinary tract infection, renal insufficiency and sepsis, they deserve clinicians' attention. This article reviews the research progress on the incidence, mechanism and risk factors of urinary calculi in patients with inflammatory bowel disease, and proposes clinically feasible prevention and intervention measures.

Non-alcoholic steatohepatitis (NASH) is characterized by hepatic cellular steatosis, inflammation, and fibrosis that can lead to end-stage liver disease and ultimately hepatocellular carcinoma. TNF-α-induce protein 8-like 1 (TIPE1), a new member of the TNF-α-induce protein 8 family, has been explored to some extent in immunology and oncology research, but its role in metabolic diseases is poorly known. In this study, C57BL/6J mice were fed with high fat and high cholesterol diet for 16 weeks to establish an animal model of NASH. It was found that the expression level of TIPE1 in the liver of NASH mice was significantly reduced compared with that of normal diet mice. In mice that specifically knocked out hepatocyte TIPE1, the degree of hepatocyte steatosis, inflammation, fibrosis, and systemic metabolic disorders induced by diet were exacerbated; In contrast, hepatocyte-specific overexpression of TIPE1 significantly prevented the progression of these abnormal pathologies, suggesting that TIPE1 has a protective effect on the liver during the pathological progression of NASH induced by high-fat and high-cholesterol diet. Under metabolic stress, TIPE1 directly interacts with apoptosis signal-regulated kinase 1 (ASK1) to inhibit its TNF receptor-associated factor 6 (TRAF6) -catalyzed polyubiquitination activation, thereby inhibiting downstream c-Jun N-terminal kinase and p38 signaling pathway, protecting hepatocytes, and alleviating the degree of hepatic steatosis, inflammation, and fibrosis. Therefore, targeting the TIPE1 or TIPE1-ASK1 axis may be a novel clinical therapeutic strategy for nonalcoholic fatty liver disease and related metabolic dysfunction diseases.

Instant detection of novel coronavirus (POCT) can effectively alleviate the crowd gathering and the number of high-frequency tests for large-scale nucleic acid screening, and the rapid results of POCT can help to quickly start tracking and isolating infected people. Especially during the outbreak of SARS-CoV-2 pneumonia, the implementation of SARS-CoV-2 POCT has great urgency and practical significance, which can quickly initiate infected person tracking, isolation and quarantine, so it is necessary to balance the need for rapid test results, quality assurance and resource availability. During periods of high epidemic incidence, the detection rate of positive cases is high, and if the detection method is highly specific, even with low sensitivity, it can provide useful information. In order to better play the detection role of POCT, equipment must be distributed quickly, which means having a supportive quality infrastructure, being ready for rapid training, and implementing testing and monitoring performance in a manner that optimizes work performance to improve possible situations. The traditional POCT quality framework is not feasible in this context and does not meet the need for rapid setup and implementation. Therefore, we need to pay attention to the standardization of sampling requirements, biosafety, POCT methods, detection performance and limitations, detection selection, detection utility, development and implementation of quality management systems, quality improvement, and medical and scientific supervision.