Changes and its influencing factors of procalcitonin in pediatric cardiac surgery under cardiopulmonary bypass / 中国胸心血管外科临床杂志

@#Objective    To explore the natural changes of procalcitonin (PCT) in the early period after pediatric cardiac surgery with cardiopulmonary bypass (CPB). Methods    A prospective and observational study was done on patients below 3 years of age, who underwent cardiac surgery involving CPB, with the risk adjustment of congenital heart surgery (RACHS) score of 2 to 5 and free from active preoperative infection or inflammatory disease. Blood samples for measurement of PCT, C-reactive protein (CRP) and white blood cell (WBC) were taken before surgery and daily for 7 days in postoperative period. Infections and complications within 7 days after operation were investigated. According to the presence or absence of infection and complications within 7 days after operation, the enrolled children were divided into an infection+complications group, a simple infection group, a simple complication group, and a normal group. Results     Finally, 429 children with PICU stay≥ 4 days were enrolled, including 268 males and 161 females, with a median age of 8.0 (0.7, 26.0) months. There were 145 children in the simple infection group, 38 children in the simple complication group, 230 children in the normal group and 16 children in the infection+complications group. The levels of PCT, CRP and WBC were significantly higher after CPB. CRP and WBC peaked on the second postoperative day (POD) and remained higher than normal until POD7. PCT peaked on POD1 and would generally decrease to normal on POD5 if without infection and complications. Age, body weight, RACHS scores, the duration of CPB and aortic cross-clamping time were correlated with PCT level. There was a statistical difference in PCT concentration between the simple infection group and the normal group on POD 3-7 (P<0.01) and a statistical difference between the simple complication group and the normal group on POD 1-7 (P<0.01). A statistical difference was found between the simple infection group and the simple complication group in PCT on POD 1-5 (P<0.05). Conclusion    WBC, CRP and PCT significantly increase after CPB in pediatric cardiac surgery patients. The factors influencing PCT concentration include age, weight, RACHS scores, CPB and aortic cross-clamping time, infection and complications.

Analysis of the change trend of etiological burden of disease of liver cancer in the Chinese population from 1990 to 2019 / 中华消化外科杂志

Objective:To investigate the change trend of etiological burden of disease of liver cancer in the Chinese population from 1990 to 2019.Methods:The descriptive epidemiologic method was conducted. Based on the Global Burden of Disease data from the Institute for Health Metrics and Evaluation at the University of Washington, the data related to liver cancer burden caused by hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcohol, nonalcoholic steatohepatitis (NASH) and other factors, including number of new cases, the crude incidence rate, age-specific incidence rate, number of deaths, crude mortality rate and age-specific mortality rate, in the Chinese population from 1990 to 2019 were collected. The age-standardized rate was calculated based on the world standardized population structure in 2019 from the Global Burden of Disease data. Observation indicators: (1) the incidence of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (2) the mortality of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (3) the change trend of age-specific incidence rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (4) the age-specific mortality rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. Count data were expressed as absolute numbers, percentages and ratio. Based on the junction point regression model, the Joinpoint software (V.4.9.1.0) was used to calculate the annual percentage change, average annual percentage change (AAPC) and 95% confidence intervals ( CI) of age-specific incidence rate and age-specific mortality rate of liver cancer caused by different etiologies. Results:(1) The incidence of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the number of new cases of liver cancer in Chinese population decreased from 236 825 to 210 462, and the crude incidence rate decreased from 20.01/100,000 to 14.80/100,000. The new cases of liver cancer caused by HBV infection, HCV infection and other factors showed a downward trend, and the absolute change rates were ?14.76%, ?3.98% and ?26.67%, respectively. The new cases of liver cancer caused by alcohol and NASH showed a increase trend, and the absolute change rates were 9.31% and 13.91%, respectively. (2) The mortality of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the number of deaths of liver cancer in Chinese population decreased from 232 449 to 187 700, and the crude mortality rate decreased from 19.64/100,000 to 13.20/100,000. The number of deaths of liver cancer caused by HBV infection, HCV infection and other factors showed a down-ward trend, and the absolute change rates were ?23.34%, ?10.99% and ?33.75%, respectively. The number of deaths of liver cancer caused by alcohol showed a slow downward trend, and the absolute change rate was ?0.51%. The number of deaths of liver cancer caused by NASH showed a increase trend, and the absolute change rate was 6.03%. (3) The change trend of age-specific incidence rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the AAPC of age-specific incidence rate of liver cancer caused by HBV infection, HCV infection, alcohol, NASH and other factors was ?3.61%(95% CI as ?4.10% to ?3.11%), ?3.57%(95% CI as ?3.99% to ?3.14%), ?2.79%(95% CI as ?3.24% to ?2.33%), ?2.65%(95% CI as ?3.09% to ?2.21%) and ?3.62%(95% CI as ?4.05% to ?3.19%), respectively. (4) The age-specific mortality rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the AAPC of age-specific mortality rate of liver cancer caused by HBV infection, HCV infection, alcohol, NASH and other factors was ?3.92%(95% CI as ?4.42% to ?3.41%), ?3.90%(95% CI as ?4.45% to ?3.35%), ?3.15%(95% CI as ?3.71% to ?2.58%), ?2.86%(95% CI as ?3.34% to ?2.38%) and ?4.09%(95% CI as ?4.64% to ?3.55%), respectively. Conclusions:From 1990 to 2019, the liver cancer burden of the Chinese population shows an overall downward trend, in which the liver cancer burden caused by HBV and HCV infection decreases the most, but HBV and HCV infection is still the main reason for the heavy burden of liver cancer. The age-specific incidence rate and age-specific mortality rate of liver cancer caused by alcohol and NASH show a downward trend, but the number of new cases of liver cancer caused by alcohol and NASH shows significant growth. The liver cancer burden caused by other factors shows a downward trend.

Influence factors of delayed recovery after right ventricular-extrapulmonary arterial conduit reconstruction / 中国小儿急救医学

Objective:To explore the risk factors of early delayed recovery after right ventricular-extrapulmonary arterial(RV-PA)conduit reconstruction.Methods:From 2017 to 2021, the children with RV-PA conduit reconstruction, who were treated in our hospital were retrospectively analyzed.The demographic data and peri-operative clinical data of the patients were collected for statistical analysis.Results:Fifty-five patients were included in the study.The patients were sequenced by the length of ICU stay.The time at the 75th percentile was defined as the critical value for grouping.According to the ICU stay time of the children, they were divided into normal recovery group(ICU stay ≤7 days, n=40)and delayed recovery group(ICU stay>7 days, n=15).The mechanical ventilator time in the whole group was 24(0, 1 408)h, and the ICU stay time was 4(1, 67)d.Six cases required extracorporeal membrane oxygenation (ECMO) support, and two cases died.In the multivariate Logistic regression analysis of two groups, long cardiopulmonary bypass(CPB) time( OR=1.034, 95% CI 1.009-1.061, P=0.009)and poor right ventricular function( OR=9.536, 95% CI 1.010-90.037, P=0.049)were independent risk factors for early delayed recovery. Conclusion:The risk of RV-PA conduit reconstruction is high.The proportion of ECMO support is increased.The mortality rate is higher.Right heart dysfunction and prolonged CPB time are risk factors for delayed postoperative recovery.

Clinical study of cytokine models to predict organ functional impairment after treatment with chimeric antigen receptor T cells in children with B-lineage lymphocytic leukemia / 中国小儿急救医学

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

Reflections on development status of Traditional Chinese Medicine in Central Asian countries / 国际中医中药杂志

Central Asia is an important hub connecting the Asian continent and European continent, and one of the key regions for China's foreign exchange and cooperation in Traditional Chinese Medicine (TCM). Central Asian countries have relatively backward medical conditions, and TCM has become an important part of local healthcare. Regulations on traditional/complementary and alternative medicine have been issued in Kyrgyzstan, Kazakhstan and Tajikistan; acupuncture and moxibustion has been covered by medical insurance in Kyrgyzstan; TCM has existed in other Central Asian countries in form of folk medicine. Central Asian countries are extremely rich in medicinal plant resources, but weak in foundation of pharmaceutical industry. Chinese government has signed cooperation agreements on TCM with many Central Asian countries, and the practical cooperation in the field of traditional medicine have continued to expand. At present, the development of TCM in Central Asian countries still faces problems such as weak foundation for the development and utilization of medicinal materials, shortage of professionals talents in TCM education and small scale of TCM clinics. In view of the above, in order to promote the dissemination and development of TCM in Central Asian countries, it is recommended that relevant units promote the establishment of joint laboratories or research centers of Chinese materia medica; give full play to local resource advantages and promote the development of medicinal plant industry; to strengthen the construction of overseas centers of TCM; actively carry out joint education or further education projects, and cultivate localized senior talents.

Progress of ketogenic diet on treatment of infantile spasms / 国际儿科学杂志

Infantile spasms(IS)is an age-dependent severe epilepsy syndrome, mainly treated with hormones and anti-seizure medications.However, due to poor efficacy and even serious side effects among some pediatric patients, searching for better alternative treatment options has become a research hotspot.In recent years, as a special diet treatment, ketogenic diet(KD)has been widely studied and gradually applied to the clinical treatment of IS, which has achieved satisfactory results.This article briefly reviews the KD regimen and mechanism of action, and focuses on the research progress in efficacy, safety and short-term prognosis of KD in the treatment of IS, whose purpose is to provide effective reference for clinical application.

Summary and analysis of total auricle reconstruction in adult microtia patients / 中华耳鼻咽喉头颈外科杂志

Objective: To observe the clinical effect of auricle reconstruction in adult patients with microtia and summarize the experience. Methods: Clinical data of adult patients with microtia who underwent total auricle reconstruction using the modified Nagata's two stage for microtia reconstruction from June 2016 to June 2021 were analyzed. A total of 41 adult patients (42 ears) with microtia were enrolled, including 30 males and 11 females, with the median age at the time of surgery of 37 years. Autogenous costal cartilage was used as the auricular framework for all patients in this group. The first stage surgery was performed according to the modified Nagata's two stage for microtia reconstruction procedure,cartilage auricular framework carving was performed by different methods according to the ossification state of adult costal cartilage. Six months following the primary operation, ear elevation and cranioauricular angle formation, retroauricular facial flap transfer and medium-thick skin grafting were performed in the second stage. Results: All patients successfully completed two stage operation. During the follow-up of 3 months and 24 months, all the 41 patients were satisfied with the morphology of reconstructed auricle. Conclusion: According to the costal cartilage status of adult patients, different costal cartilage carving techniques can be used for total auricle reconstruction to obtain ideal surgical results.

Analysis of clinicopathological characteristics of non-alcoholic fatty liver disease / 中华病理学杂志

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg2 combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.

Progress of research on chitosan-based microspheres in oral tissue lesions / 口腔医学

@#Chitosan-based microspheres use chitosan as the main material to obtain particles with special structures through microsphere processing technology. They have the ability of slow and controlled release of drugs and the role of scaffolding, which have great application prospect in stomatology, but the application of chitosan-based microspheres is still in the research stage and has not yet been applied in clinical practice. This article reviews progress of domestic and foreign research on chitosan-based microspheres, in aspects of treatment of oral and jawbone tissue defects, periodontal diseases, dental pulp diseases and nerve tissue injury, in order to provide reference for follow-up research.

Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial-mesenchymal transition via directly targeting TGFβR1

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).

Neuron stem cell NLRP6 sustains hippocampal neurogenesis to resist stress-induced depression

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Preparation and identification of rabbit anti-mouse coiled-coil domain containing 189(Ccdc189)polyclonal antibody / 细胞与分子免疫学杂志

Objective To prepare a rabbit anti-mouse coiled-coil domain containing 189 (Ccdc189) polyclonal antibody. Methods The pET-28a-Ccdc189 prokaryotic expression plasmid was constructed and transformed into E.coli BL21. IPTG was used to induce the expression of Ccdc189 prokaryotic protein. Adult male New Zealand rabbits were immunized with purified recombinant protein to obtain rabbit anti-mouse Ccdc189 polyclonal antibody. The specificity of the polyclonal antibody was identified by Western blot analysis, indirect ELISA and immunofluorescence histochemical staining. Results The pET-28a-Ccdc189 recombinant plasmid was successfully constructed and the expression of the Ccdc189 recombinant protein was induced. ELISA revealed that the titer of the polyclonal antibody was 1:1 000 000. Western blot and immunofluorescence staining demonstrated that the Ccdc189 polyclonal antibody could specifically identify the Ccdc189 prokaryotic protein and the Ccdc189 protein in adult wild-type mouse testis. Conclusion A polyclonal antibody with high specificity against mouse Ccdc189 was successfully created.

Application of absorbable anchor combined with Kirschner wire in reconstruction of extension function of old mallet finger / 中国修复重建外科杂志

OBJECTIVE@#To investigate the feasibility and effectiveness of absorbable anchor combined with Kirschner wire fixation in the reconstruction of extension function of old mallet finger.@*METHODS@#Between January 2020 and January 2022, 23 cases of old mallet fingers were treated. There were 17 males and 6 females with an average age of 42 years (range, 18-70 years). The cause of injury included sports impact injury in 12 cases, sprain in 9 cases, and previous cut injury in 2 cases. The affected finger included index finger in 4 cases, middle finger in 5 cases, ring finger in 9 cases, and little finger in 5 cases. There were 18 patients of tendinous mallet fingers (Doyle type Ⅰ), 5 patients were only small bone fragments avulsion (Wehbe type ⅠA). The time from injury to operation was 45-120 days, with an average of 67 days. The patients were treated with Kirschner wire to fix the distal interphalangeal joint in a mild back extension position after joint release. The insertion of extensor tendon was reconstructed and fixed with absorbable anchors. After 6 weeks, the Kirschner wire was removed, and the patients started joint flexion and extension training.@*RESULTS@#The postoperative follow-up ranged from 4 to 24 months (mean, 9 months). The wounds healed by first intention without complications such as skin necrosis, wound infection, and nail deformity. The distal interphalangeal joint was not stiff, the joint space was good, and there was no complication such as pain and osteoarthritis. At last follow-up, according to Crawford function evaluation standard, 12 cases were excellent, 9 cases were good, 2 cases were fair, and the good and excellent rate was 91.3%.@*CONCLUSION@#Absorbable anchor combined with Kirschner wire fixation can be used to reconstruct the extension function of old mallet finger, which has the advantages of simple operation and less complications.

Discussion on "sugar needle - comfortable acupuncture and moxibustion" / 中国针灸

The cases of feeling comfort during acupuncture and moxibustion treatment in literature were summarized and its biological basis was explored. A simple classification of comfort was made, and the importance of obtaining comfort in acupuncture treatment was pointed out. Considering the pursuit of less pain and harmlessness in modern clinical treatment, sugar needle should be advocated and popularized in current clinical practice of acupuncture and moxibustion.

Clinical analysis of immunotherapy rechallenge in advanced gastric cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Global trajectories of liver cancer burden from 1990 to 2019 and projection to 2035 / 中华医学杂志(英文版)

BACKGROUND@#Large disparities exist in liver cancer burden trends across countries but are poorly understood. We aimed to investigate the global trajectories of liver cancer burden, explore the driving forces, and predict future trends.@*METHODS@#Data on the liver cancer burden in 204 countries and territories from 1990 to 2019 were extracted from the Global Burden of Disease Study. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) trajectories were defined using growth mixture models. Five major risk factors contributing to changes in the ASIR or ASMR and socioeconomic determinants were explored using the identified trajectories. A Bayesian age-period-cohort model was used to predict future trends through 2035.@*RESULTS@#Three trajectories of liver cancer burden were identified: increasing, stable, and decreasing groups. Almost half of the American countries were classified in the decreasing group (48.6% for ASIR and ASMR), and the increasing group was the most common in the European region (ASIR, 49.1%; ASMR, 37.7%). In the decreasing group, the decrease of liver cancer due to hepatitis B contributed 63.4% and 60.4% of the total decreases in ASIR and ASMR, respectively. The increase of liver cancer due to alcohol use, hepatitis C, and hepatitis B contributed the most to the increase in the increasing group (30.8%, 31.1%, and 24.2% for ASIR; 33.7%, 30.2%, and 22.2% for ASMR, respectively). The increasing group was associated with a higher sociodemographic index, gross domestic product per capita, health expenditure per capita, and universal health coverage (all P <0.05). Significant variations in disease burden are predicted to continue through 2035, with a disproportionate burden in the decreasing group.@*CONCLUSION@#Global disparities were observed in liver cancer burden trajectories. Hepatitis B, alcohol use, and hepatitis C were identified as driving forces in different regions.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR) / 中华医学杂志(英文版)

BACKGROUND@#The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.@*METHODS@#Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts.@*RESULTS@#In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use.@*CONCLUSIONS@#Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Rapid prediction of G protein-coupled receptor structures using nanoluciferase assay / 药学学报

Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.