[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

No causal effects between rosiglitazone and cardiovascular disease or risk factors: a Mendelian randomization study.

OBJECTIVE: Although many observational studies have shown an association between rosiglitazone and cardiovascular disease (CVD) or risk factors, controversy remains. We conducted a Mendelian randomized (MR) study to explore whether rosiglitazone is causally related to CVDs and risk factors. PATIENTS AND METHODS: Single-nucleotide polymorphisms associated with rosiglitazone at genome-wide significance were identified from a genome-wide association study of 337,159 European-ancestry individuals. Four treatments with rosiglitazone-associated single-nucleotide polymorphisms associated with a higher risk of CVDs were used as an instrumental variable (IV). Summary-level data for 7 CVDs and 7 risk factors were obtained from UK Biobank and consortia. RESULTS: We found no causal effects of rosiglitazone, either on CVDs or risk factors. The results were consistent in sensitivity analyses using Cochran's Q test, MR-PRESSO method, leave-one-out analysis and Mendelian randomization-Egger method (MR-Egger), and no directional pleiotropy was observed. Sensitivity analyses confirmed that rosiglitazone was not significantly associated with CVDs and risk factors. CONCLUSIONS: The findings from this MR study indicate no causal relationship between rosiglitazone and CVDs or risk factors. Hence, previous observational studies may have been biased.

Characteristics of atmospheric ice nucleating particles over East Antarctica retrieved from the surface snow.

The concentration of ice nucleating particles (INPs) in the atmosphere is critical for understanding cloud microphysics and predicting the climate system. In this study, we collected surface snow samples along a traverse route from the coastal to the inland of East Antarctica to analyze INP concentrations and identify their spatial variations using a droplet freezing device. The overall concentration of INPs was found to be considerably low along the route, averaging at 0.8 ± 0.8 × 105 L-1 in water and 4.2 ± 4.8 × 10-3 L-1 in air at -20 °C. Although coastal areas had higher levels of sea salt species compared to inland regions, the concentration of INPs remained consistent along the route suggesting less important origination of INPs from the around ocean. Additionally, the heating experiment revealed the important contribution of proteinaceous INPs indicating the presence of biological INPs (bio-INPs). The fraction of bio-INPs was 0.52 on average at -20 °C and ranged from 0.1 to 0.7 from -30 °C to -15 °C. Finally, we parameterize the atmospheric INP concentrations as a function of freezing temperature which can be useful for modeling INP concentrations in this region.

[Establishment of a prognostic model for non-nephrotic membranous nephropathy based on unbalanced data].

Objective: To explore the construction of a machine learning model based on unbalanced data to predict the progression of non-nephrotic membranous nephropathy. Methods: The clinical and pathological data of patients diagnosed with non-nephrotic membranous nephropathy by renal biopsy in Shanxi People's Hospital from January 2018 to December 2021 were retrospectively analyzed.The prediction models were constructed based on logistic regression, support vector machine (SVM) and light gradient boosting machine (lightGBM), respectively. The mixed sampling technology was used to process the unbalanced data, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive performance of the models. Finally, Shapley additive explanation (SHAP) was used to interpret the results of the optimal prediction model. Results: A total of 148 patients were included in the study, including 84 males and 64 females, with a mean age of (47.2±12.5) years. The follow-up time [M(Q1, Q3)] was 14(7, 20) months. Twenty-three patients (15.5%) achieved the renal end-point event in the study. The SVM model had the highest AUC (0.868, 95%CI: 0.813-0.925), followed by logistic regression (AUC=0.865, 95%CI: 0.755-0.899) and lightGBM (AUC=0.791, 95%CI: 0.690-0.882). The feature recursive elimination cross validation (RFECV) method based on random forest (RF) and the SHAP plot based on the SVM model showed that immunohistochemistry IgG, total protein (TP), anti-phospholipase A2 receptor (anti-PLA2R), blood chloride and D-Dimer were risk factors affecting the progress of non-nephrotic membranous nephropathy. Moreover, patients with high immunohistochemistry IgG, anti-PLA2R and D-Dimer had an increased risk of achieving the renal end-point event. Conclusion: The SVM model established in this study can effectively predict the progress of non-nephrotic membranous nephropathy, and provide a new method for the early identification of high-risk patients and precision therapy.

Combined training prescriptions for improving cardiorespiratory fitness, physical fitness, body composition, and cardiometabolic risk factors in older adults: Systematic review and meta-analysis of controlled trials.

Background: Improved physical fitness is important for preventing COVID-19-related mortality. So, combined training can effectively increase peak oxygen consumption, physical fitness, body composition, blood pressure, and the healthrelated characteristics of adults; however, its impact in the elderly remains unclear. Methods: This systematic review and meta-analysis aimed to evaluate the effects of combined training on older adults. Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until April 2021) for randomized trials comparing the effect of combined training on cardiorespiratory fitness, physical fitness, body composition, blood pressure, and cardiometabolic risk factors in older adults. Results: Combined training significantly improved peak oxygen consumption compared to no exercise (WMD = 3.10, 95% CI: 2.83 to 3.37). Combined resistance and aerobic training induced favorable changes in physical fitness (timed up-and-go = -1.06, 30-s chair stand = 3.85, sit and reach = 4.43, 6-minute walking test = 39.22, arm curl = 4.60, grip strength = 3.65, 10-m walk = -0.47, maximum walking speed = 0.15, one-leg balance = 2.71), body composition (fat mass = -2.91, body fat% = -2.31, body mass index = -0.87, waist circumference = -2.91), blood pressure (systolic blood pressure = -8.11, diastolic blood pressure = -4.55), and cardiometabolic risk factors (glucose = -0.53, HOMA-IR = -0.14, high-density lipoprotein = 2.32, total cholesterol = -5.32) in older individuals. Finally, the optimal exercise prescription was ≥ 30 min/session × 50-80% VO2peak, ≥ 3 times/week for ≥ 12 weeks and resistance intensity 70-75% one-repetition maximum, 8-12 repetitions × 3 sets. Conclusions: Combined training improved VO2peak and some cardiometabolic risk factors in older populations. The dose-effect relationship varied between different parameters. Exercise prescriptions must be formulated considering individual needs during exercise.

Contexte: L'amélioration de la condition physique est importante pour prévenir la mortalité liée au COVID-19. Ainsi, l'entraînement combiné peut augmenter efficacement la consommation maximale d'oxygène, la forme physique, la composition corporelle, la tension artérielle et les caractéristiques liées à la santé des adultes; cependant, son impact chez les personnes âgées reste incertain. Méthodes: Cette revue systématique et cette méta-analyse visaient à évaluer les effets de l'entraînement combiné chez les personnes âgées. Quatre bases de données électroniques (PubMed, Scopus, Medline et Web of Science) ont été consultées (jusqu'en avril 2021) pour trouver des essais randomisés comparant l'effet d'un entraînement combiné sur l'aptitude cardiorespiratoire, la forme physique, la composition corporelle, la tension artérielle et les facteurs de risque cardiométabolique chez les personnes âgées. Résultats: Au total, 37 publications ont été incluses dans cette étude. L'entraînement combiné a considérablement amélioré la consommation maximale d'oxygène par rapport à l'absence d'exercice (DMP = 3,10, IC95 % : 2,83 à 3,37). La combinaison résistance + entraînement aérobie a entraîné des changements favorables dans la forme physique (démarrage chronométré = −1,06, position assise pendant 30 s = 3,85, position assise et lever = 4,43, test de marche de 6 minutes = 39,22, flexion des bras = 4,60, adhérence force = 3,65, marche de 10 m = −0,47, vitesse de marche maximale = 0,15, équilibre sur une jambe = 2,71), composition corporelle (masse grasse = −2,91, pourcentage de graisse corporelle = −2,31, indice de masse corporelle = −0,87, taille circonférence = −2,91), tension artérielle (pression artérielle systolique = −8,11, pression artérielle diastolique = −4,55) et facteurs de risque cardiométabolique (glucose = −0,53, HOMA-IR = −0,14, lipoprotéines de haute densité = 2,32, cholestérol total = −5,32) chez les personnes âgées. Enfin, la prescription d'exercice optimale était ≥ 30 min/séance × 50­80 % VO2pic, ≥ 3 fois/semaine pendant ≥ 12 semaines et résistance à une intensité de 70­75 % une répétition maximale, 8­12 répétitions × 3 séries. Conclusions: L'entraînement combiné a amélioré la VO2pic et certains facteurs de risque cardiométabolique chez les populations âgées. La relation dose-effet variait entre les différents paramètres. Les prescriptions d'exercice doivent être formulées en tenant compte des besoins individuels pendant l'exercice.

[A comparison of current guidelines for the management of intrahepatic cholangiocarcinoma worldwide].

Intrahepatic cholangiocarcinoma (ICC) is the second most common human liver malignancy and its incidence rate has been gradually increasing worldwide over the past decades. Surgical resection (R0 resection) is the preferred potentially curative treatment for ICC patients. However, due to its conceal clinical features and high invasiveness, most patients have lost the opportunity for surgical resection at the time of diagnosis. In recent years, with the rapid development of targeted therapy and immunotherapy, which is represented by immune checkpoint inhibitors, clinicians are expected to provide more effective treatment options for patients with mid-stage or advanced ICC. At present, there are still controversial opinions on different guidelines regarding preoperative biliary drainage, the extent of hepatectomy, the definition of R0 resection, the width of the resection margin, lymph node dissection, postoperative recurrence, adjuvant therapy, etc. In this review, 12 guidelines or expert consensus published worldwide from 2012 to 2022 (including 4 Chinese guidelines, 4 European guidelines, 2 American guidelines and 2 Japanese guidelines) were retrieved. Focusing on sorting and comparing the current views on clinical management of ICC in different guidelines, this review aims to provide reference information for ICC clinical management and decision-making.

[Analysis of perioperative efficacy and safety of cytoreductive surgery in the treatment of colorectal cancer peritoneal metastases].

Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.

[Study on the protective effect of cooling the surface of frozen water on renal function in robotic-assisted laparoscopic nephrect].

Objective: To compare the effects of ice water kidney cooling and traditional non-cooling surgery on postoperative renal function in robot-assisted laparoscopic partial nephrectomy, and explore its clinical value in protecting renal function. Methods: A retrospective analysis is conducted on the base of the clinical data of patients undergoing robot-assisted laparoscopic partial nephrectomy in Second Affiliated Hospital of Navy Military Medical University from January to November 2019. A total of 89 cases, of which 21 cases were treated with ice water to cool the kidney surface and block the renal artery during the operation (cooling group); 68 cases only clamp the renal artery (control group). Compare the difference of the operation time, R.E.N.A.L. score, intraoperative blood loss, renal artery block of time,postoperative intestinal recovery time, cut edge positive rate, preoperative and postoperative blood electrolyte levels, the change of blood creatinine and GFR before operation and the first and third months after the operation and other indicators between two groups. Results: All the 89 patients completed the operation normally, and no conversion to open surgery or to general endoscopic surgery. The two groups of patients had statistically significant differences in tumor diameter [7.0(5.5, 8.0) vs 3.8(3.0, 5.0) cm, P<0.001], R.E.N.A.L. score [8.0(6.5, 8.0) vs 6.0(5.0, 8.0), P=0.003], Chloride (Cl-) in the blood [(103.29±2.81) vs (104.74±2.58) mmol/L, P=0.030], (P<0.05) in the preoperative data. There were significant differences in renal artery occlusion time [20.0(18.5, 27.5) vs 19.0(15.0, 21.0) min, P=0.023] and operation time [168.0(130.0, 182.5) vs 130.0(110.0, 177.5) min, P=0.007] between the two groups (P<0.05). There was no significant difference in the blood creatinine after one or 3 month as well as for the glomerular filtration rate (all P>0.05). After follow-up for 3-24 months, no tumor recurrence or distant metastasis occurred in both groups, and no related complications caused by ice-free Water Cooling Technique in the cooling group. Conclusions: It is safe and effective to apply kidney surface cooling technique with ice water in robot-assisted laparoscopic partial nephrectomy for complex kidney tumor. It can significantly reduce the renal parenchyma warm ischemia injury of renal parenchyma. And it's conducive to the recovery of patients with postoperative renal function, which can maximize the protection of renal function of patients.

[Meta analysis of whether cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy can improve survival in patients with colorectal cancer peritoneal metastasis].

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.

[Expression of circ-KEL in acute myeloid leukemia and its regulatory mechanisms in leukemic cells].

Objective: To explore the expression of circ-KEL in patients with acute myeloid leukemia (AML) and the effect and mechanism of circ-KEL on leukemic cells. Methods: The expression of circ-KEL was detected by quantitative real-time polymerase chain reaction in bone marrow mononuclear cells collected from 116 patients with AML and 40 healthy donors. The correlation of circ-KEL expression with the clinical characteristics of patients with AML was further systematically analyzed. The modulations among circ-KEL, miR-335-5p, and LRG1 were predicted through bioinformatics analysis and validated by dual luciferase assay. Cell proliferation and apoptosis were detected using CCK8 and flow cytometry. Results: The expression of circ-KEL was significantly elevated in patients with AML compared with the healthy controls (Relative expression level, -Δct, AML: -7.117±1.831; control: -8.669±1.771, P<0.001) . Moreover, patients with high circ-KEL expression have significantly worse overall survival. The level of circ-KEL in patients with AML was downregulated after chemo-treatment. In addition, circ-KEL could serve as the sponge of miR-335-5p and regulate LRG1. Bioinformatics analysis showed that miR-335-5p correlates with good prognosis and was negatively associated with LRG1. LRG1 could promote cell proliferation and inhibit cell apoptosis. Our results also exhibited the higher expression of LRG1 in patients with AML. Moreover, circ-KEL exerted functional effects via sponging miR-335-5p and regulating LRG1. Conclusion: circ-KEL expresses highly in patients with AML and correlates with poor prognosis, suggesting its important role in the genesis and progress of AML.

[Analysis on medical observation of 1 665 close contacts of COVID-19 cases].

Objective: To understand the identification and medical observation of close contacts of COVID-19 cases in a city and provide scientific basis for the adjustment of the epidemic prevention and control strategies. Methods: Descriptive epidemiological methods were used to analyze the general characteristics of all the close contacts of COVID-19 cases in a city. Throat swabs were collected from the close contacts for real-time fluorescent RT-PCR. The confirmed cases were diagnosed according to diagnosis and treatment of COVID-19 (trial version 5). Results: Among the 1 665 close contacts of COVID-19 cases in a city, 10 were diagnosed as COVID-19 cases during the medical observation period, accounting for 30.30% of all the confirmed cases in a city, most of them were close relatives of the confirmed cases. The longest contact time with the confirmed cases was 8 days and the shortest was 0 days. Ten COVID-19 cases in close contacts constituted to six family clusters. Conclusions: In COVID-19 prevention and control in a city, the active tracking of the transmission chains of the confirmed cases and timely identification of the close contacts were conducted. The people who had close contacts with the confirmed COVID-19 cases within 14 days before onset were all placed under medical observation, which played a key role in the effective prevention and control of COVID-19 epidemic in a city. Nearly one third of COVID-19 cases occurred during the medical observation period, so the infection sources were effectively controlled and transmission routes were effectively blocked, which greatly facilitated the prevention of the clusters of COVID-19 cases.

[Research progress of immunotherapy alone and in combination for liver cancer].

Presently, the incidence of hepatocellular carcinoma (HCC) ranks fourth among common malignant tumors in China, and the mortality rate ranks second. The preferred method of clinical treatment for HCC is early surgical resection at this time, but most patients have reached to mid-advanced stage at the time of diagnosis, so surgery cannot be performed. Traditional radiotherapy and chemotherapy have poor prognosis and many adverse reactions, which make the current clinical treatment of HCC in China full of challenges. Therefore, new treatment strategies are urgently needed to improve the quality of life of liver cancer patients. With the advancement of modern medicine, the treatment of liver cancer is no longer limited to traditional treatments. Immunotherapy as a new treatment has become an important treatment for liver cancer. In recent years, immunotherapy and new targeted drugs for liver cancer have become a research hotspot, and many achievements have been made in the treatment of liver cancer. In this paper, the current situation and progress of single or combined immunotherapy for liver cancer of recent years are briefly reviewed.

[Progress in diagnosis and treatment of rectal neuroendocrine neoplasms].

Neuroendocrine neoplasms (NENs) are relatively rare heterogeneous tumors that originate from peptidergic neurons and neuroendocrine cells and have been referred to as "carcinoids" in the past. Although this type of tumor had been previously considered to be indolent tumor with a low degree of malignancy, with the development of medicine and clinical study, researchers found that NENs had the potential to metastasize. They can occur in any part of the body where neuroendocrine cells are distributed and gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are the most common type of NENs.Due to the improvement of techniques such as endoscopy and imaging, the incidence of rectal neuroendocrine tumors(R-NENs) and the number of related clinical researches have both increased significantly in recent years. Although researches in Chinese and foreign medical centers are mostly retrospective studies of small samples and the efficacies of different treatment methods are still under debating and lack of sufficient medical evidence to support, the diagnosis and treatment of this disease is gradually becoming standardized according to the proposal of corresponding guidelines. The recent advances in the epidemiology, diagnosis and treatment of rectal neuroendocrine neoplasms are reviewed in this paper.

[Clinicopathological characteristics of adult T cell leukemia/lymphoma].

Objective: To investigate the clinical presentation, clinicopathologic features, diagnosis and differential diagnosis of adult T cell leukemia/lymphoma (ATLL). Methods: Four cases of ATLL from Fujian Cancer Hospital between October 2017 and May 2018 were analyzed using hematoxylin-eosin and immunohistochemical stains and polymerase chain reaction (PCR) for HTLV-1 provirus genes. The relevant literature was reviewed. Results: There were two males and two females, age range 38-80 years. All patients were from coastal cities of Fujian province. Clinical presentations including lymphadenopathy, hepatomegaly and splenomegaly were detected in most patients; skin lesion, hypercalcemia and lymphocytosis were also commonly detected.Histologically, there was diffuse effacement of the normal architecture by tumor cells infiltration. The inflammatory background is usually sparse, with scanty eosinophils. The atypical lymphoid cells were typically medium to large sized with pronounced nuclear pleomorphism, irregular nuclei, chromatin clumping and prominent nucleoli. Blast-like cells with transformed nuclei were present in variable proportions. Giant cells with convoluted or cerebriform nuclear contours may be present. Rare cases may be composed predominantly of anaplastic tumor cells. Characteristic "flower cells" with large multi-lobated nuclei can be seen. The tumor cells were strongly positive for CD2, CD3, CD5, CD4 and CD25, but negative for CD7, CD8 and cytotoxic molecules (including TIA-1, Granzyme B and perforin). In three cases, the large transformed cells were positive for CD30. In one case, the anaplastic large cells were diffusely and strongly positive for CD30. All cases were negative for EBER, but positive for HTLV-1 provirus. Conclusions: ATLL is a rare type of T cell lymphoma with unique clinical and pathological features, and should be distinguished from peripheral T cell lymphoma, NOS, ALK negative anaplastic large cell lymphoma and mycosis fungoides. Hypercalcemia, systemic disease, characteristic "flower cells" and specific immunophenotypic profile of CD3(+), CD4(+), CD25(+), and CD7(-) are highly suggestive. However, ATLL can only be confirmed if the presence of HTLV-1 provirus.

[The characteristic of hereditary spherocytosis related gene mutation in 37 Chinese hereditary spherocytisis patients].

Objective: To reveal the genetic characteristics of erythrocyte membrane protein in hereditary spherocytosis (HS) in China. Methods: Next-generation sequencing technology was used to detect mutations in genes of erythrocyte membrane proteins in 51 clinically diagnosed HS patients. The relationship between gene mutations and clinical phenotypes was analyzed. Results: Mutations in erythrocyte membrane protein genes were detected in 37 patients, including 17 with ANK1 mutations (17/37, 45.9%), 14 with SPTB mutations (14/37, 37.8%), and 5 with SLC4A1 mutations (5/37, 13.5%). One patient carried both heterozygous ANK1 mutation and SPTB mutation (1/37, 2.7%). SPTA1 and EPB42 mutation was not fou nd in any patient. Nonsense mutations (36.8%) and missense mutations (31.6%) were most common. Of the 38 mutations detected, 34 were novel mutations and have not been reported elsewhere (89.5%). Sixteen HS patients underwent parental genetic validation, 6 patients (37.5%) inherited gene mutation from parents and 10 (62.5%) were de novo. The peripheral blood cell parameters of HS patients were not related to the mutant genes and gene mutation types. However, it seems that HS patients with mild clinical status are prone to carry SPTB mutations while more patients with severe clinical status have ANK1 mutations. Conclusions: ANK1 and SPTB are the most common mutant genes in Chinese HS patients, mainly with missense mutations and nonsense mutations. There was no significant correlation between the mutation of HS related genes and the severity of HS.

[The clinical and laboratory characteristics of congenital pyruvate kinase deficiency].

Clinical data of 19 patients with congenital pyruvate kinase deficiency were analyzed. Insufficient pyruvate kinase confirmed the diagnosis. Laboratory parameters of hemolysis were summarized. In cases of neonatal hyperbilirubinemia and unexplained hemolytic anemia, pyruvate kinase activity and next generation sequencing test may help the early diagnosis.

[Using target next-generation sequencing assay in diagnosing of 46 patients with suspected congenital anemias].

Objective: To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias. Methods: Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017. Results: A total of 46 patients were enrolled in this study, the clinical suspection were 11 cases Fanconi anemia (FA), 8 cases congenital dyserythropoietic anemia (CDA), 6 cases congenital sideroblast anemia (CSA), 12 cases congenital hemolytic anemia (CHA), 1 case dyskeratosis congenital (DC), 4 cases iron-refractory iron deficiency anemia and 4 cases unexplained cytopenia (Uc), respectively. 28 (60.9%) of 46 patients became confirmed cases after targeted NGS, corresponding to 44 mutations of which 33 were new. 26(56.5%) patients with results of the assay matching to clinical suspection, including FA (5/11, 45.5%), CSA (6/6, 100.0%), CDA (3/8, 37.5%) and CHA (12/12, 100.0%). 2 (4.3%) cases not matching to clinical suspection, including dyskeratosis congenital (DC) was made in 1(2.2%) patients with suspected FA and familial hemophagocytic lymphohistiocytosis (FHL) was made in 1(2.2%) patients with suspected unexplained cytopenia (Uc). In 12 CHA patients, the hemolytic type was further clarified by the NGS. The remaining 18 cases were not clearly diagnosed. Conclusion: Targeted NGS assay is of major impact on congenital anemias. The assay should be used routinely in congenital anemias.