Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia / 中华儿科杂志

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Drug resistance and genetic diversity of clinical strains of Helicobacter pylori in the Qiannan Prefecture and Guiyang City,and their relationships with diseases / 中国人兽共患病学报

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6％(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4％in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Construction and prospect of healthy enterprises in the new era / 中华劳动卫生职业病杂志

The construction of health enterprises practice the concept of big health. It is an important solution to protect the overall health of occupational groups in the new era, which is of great significance to promoting a healthy city and helping to build a healthy China. This paper clarifies the connotation of healthy enterprises in the new era, discusses the key points of healthy enterprise construction around the "four in one" construction content, "PDCA" construction procedures, and evaluation methods of healthy enterprises. It focuses on the progress of healthy enterprise construction, analyzes the problems faced by the construction of health enterprises in China, and puts forward suggestions to improve the construction efficiency, with a view to providing ideas for further promoting the construction of health enterprises in China.

Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial / 亚洲男科学杂志(英文版)

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

Association between cardiovascular implantable electronic devices and tricuspid regurgitation: a case-control study / 世界急诊医学杂志（英文）

@#Cardiovascular implantable electronic devices (CIEDs) are widely used in the modern era. Every year, about 730,000 permanent pacemakers and 330,000 CIEDs are implanted worldwide. CIEDs have been known to increase the life expectancy of millions of people and improve their quality of life by controlling the heart rate and atrioventricular and interventricular synchronization and preventing sudden cardiac death.[1] The tricuspid valve consists of the annulus, leaflets, chordae tendineae, and papillary muscles. Interaction between the endocardial lead and any component of this structure can lead to tricuspid valve dysfunction, thereby resulting in tricuspid regurgitation (TR).[2] CIED-related TR has been shown to be an independent predictor of hospitalization for heart failure.[3,4]

Mechanism of Modified Shengjiangsan in Treatment of IgA Nephropathy Based on Network Pharmacology， Molecular Docking， and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， targets， and signaling pathways of modified Shengjiangsan in the treatment of immunoglobulin A nephropathy （IgAN） based on network pharmacology， and to explore its underlying mechanism through molecular docking and experimental verification on animals. MethodThe active ingredients and related targets of modified Shengjiangsan were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）， UniProt， SwissTargetPrediction， and literature review. IgAN-related targets were obtained from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Cytoscape 3.9.0 was used to construct the regulation network of the related targets of Shengjiangsan and IgAN， and the protein-protein interaction （PPI） network was plotted by STRING. The common genes were analyzed for gene ontology （GO） functional annotation and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment by Metascape. Key targets and main active ingredients were selected for molecular docking by AutoDockTools 1.5.6. The experimental model of IgAN was induced by bovine serum albumin（BSA， ig） combined with lipopolysaccharide （LPS， iv） and the complex of CCl4 and castor oil （sc） in rats. The model rats were treated with modified Shengjiangsan and benazepril hydrochloride for four weeks. The rats were sacrificed after drug administration. The levels of transforming growth factor-β1 （TGF-β1） and interleukin-6 （IL-6） in the serum and kidney tissues were detected by enzyme-linked immunosorbent assay（ELISA）， immunohistochemistry， Real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot. ResultA total of 105 active ingredients were obtained according to oral bioavailability（OB）， drug-likeness（DL）， and literature screening. There were 124 common genes and 59 core targets. Neurotrophic tyrosine receptor kinase 1 （NTRK1）， cullin-3 （CUL3）， tumor protein 53 （TP53）， epidermal growth factor receptor （EGFR）， exportin 1 （XPO1）， and other targets might be closely related to IgAN. As predicted by KEGG enrichment analysis， the treatment of IgAN with modified Shengjiangsan mainly involved the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， nuclear transcription factor-kappa B （NF-κB） signaling pathway， and cytokine-cytokine receptor interaction signaling pathway. As revealed by molecular docking， the main active ingredients in modified Shengjiangsan showed stable binding activities with NTRK1， CUL3， TP53， EGFR， and XPO1 in the core targets， indicating that it presumedly regulated inflammatory responses by affecting NTRK1， CUL3， TP53， EGFR， and XPO1 target proteins. The results of experimental verification on animals showed that the expression levels of cytokines TGF-β1 and IL-6 in the serum and kidney tissues of IgAN rats were significantly decreased by modified Shengjiangsan， suggesting that Shengjiangsan might inhibit excessive fibrosis， and inflammatory and immune responses by regulating signaling pathways such as cytokine-cytokine receptor interaction， PI3K/Akt， and NF-κB. ConclusionModified Shengjiangsan may treat IgAN through multiple targets and pathways. Its mechanism may be related to the inhibition of excessive fibrosis， and inflammatory and immune responses by affecting the expression of NTRK1， CUL3， TP53， EGFR， and XPO1 and the regulation of the cytokine-cytokine receptor interaction， PI3K/Akt， NF-κB， and other signaling pathways.

Roles of Pyroptosis and Necroptosis in Diabetic Kidney Disease and Its Regulation with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

The increasing incidence of obesity and diabetes has made diabetic kidney disease （DKD） the main cause of chronic kidney disease and end-stage renal disease. Despite current pharmacological interventions for blood glucose control and renin-angiotensin system inhibition， the risk of kidney disease progression and complications remains high. At present， the pathogenesis of DKD has been clarified to be related to chronic inflammatory response， oxidative stress， glucose and lipid metabolism disorders， and hemodynamic abnormalities. According to recent studies， the programmed cell deaths （PCD） of renal intrinsic cells such as pyroptosis and necroptosis play a key role in the occurrence and development of DKD. Pyroptosis and necroptosis， the two newly discovered routes of PCD， can protect the hosts from being invaded by microbial pathogens， but their dysregulation is associated with multiple autoimmunity and autoinflammatory responses. Pyroptosis and necroptosis are closely interlinked and cross-regulated. Different from apoptosis， these two cellular suicide mechanisms cause membrane rupture and release of cell contents through their respective gasdermin D （GSDMD） and mixed lineage kinase domain-like protein （MLKL）， with damage-associated molecular patterns （DAMPs） and inflammatory cytokines like interleukin-1β （IL-1β） involved to trigger inflammation， and chronic inflammatory responses are key factors leading to the progression of DKD. Traditional Chinese medicine （TCM） has long been employed for the prevention and treatment of DKD and the resulting clinical outcomes are remarkable. TCM has been proved to exert a protective effect against DKD by affecting the expression of nucleotide oligomerization domain-like receptor protein 3 （NLRP3） inflammasome， receptor-interacting protein kinase 3 （RIPK3）， and MLKL. This paper reviewed the relationship of pyroptosis and necroptosis with DKD and its intervention with TCM.

Associations of Daytime Napping with Incident Cardiovascular Diseases and Hypertension in Chinese Adults: A Nationwide Cohort Study / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to examine the associations of daytime napping with incident risks of cardiovascular diseases (CVDs) and hypertension (HTN).@*METHODS@#Data for napping and CVD outcomes in 25 provinces were collected from baseline (2010) and three waves of follow-up (2012-2017) investigations of the China Family Panel Studies. Cox frailty models with random intercepts for the surveyed provinces were used to assess the longitudinal effects of daytime napping on CVD and HTN.@*RESULTS@#Compared with non-nappers, 30+ min nappers had higher risks of CVD and HTN, while no significant associations were observed among < 30 min nappers. Incident risks among 30- to < 60-min nappers increased by 22% [hazard ratio (HR) 1.22, 95% confidence interval ( CI) 1.08-1.39] for CVD and 21% (1.21, 1.04-1.41) for HTN, respectively, with corresponding HRs of CVD and HTN of 1.27 (1.09-1.47) and 1.38 (1.16-1.65) among ≥ 60 min nappers. Nap-associated CVD risks varied by subgroups, with stronger associations in participants with lower body mass index (< 24 kg/m 2), physically inactive persons, smokers, and participants with longer nighttime sleep (≥ 7 h/night). Significant effects of daytime napping were observed on rural and northern residents only, highlighting great regional variations in CVD risks associated with napping habits.@*CONCLUSIONS@#This cohort study revealed strong evidence that long daytime napping (≥ 30 min) is associated with an increased incidence of cardiovascular events.

Therapeutic effect of tetrandrine on silicosis rats and its toxic effect on liver and kidney function / 中国职业医学

OBJECTIVE: To explore the therapeutic effect of tetrandrine(TET) on silicosis model rats and its toxic effect on liver and kidney function. METHODS: The specific pathogen free healthy male Wistar rats were randomly divided into the control group, the model group and the TET group, with 14 rats in each group. By un-exposure tracheal injection method, the rats in the model and TET groups were given one-time tracheal infusion of free silicon dioxide suspension with a mass concentration of 50 g/L to establish the rat model of silicosis. Rats in the control group were infused with 1 mL of 0.9% sodium chloride solution with the same method. On the second day after the model was established, the TET group was given 30 mg/kg body mass of TET solution by gavage. The other two groups were given the same amount of 0.9% sodium chloride solution. The treatment was once per day, six times per week. Seven rats in each group were sacrificed on the 28 th and 56 th days after modeling. The morphological change of the lung, liver and kidney tissues of each group was observed. The enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1), interleukin(IL)-1β and IL-6, in the lung tissues of rats in each group. The activities of aminotransferase(ALT), aspartate aminotransferase(AST) and the levels blood urea nitrogen(BUN), creatinine(CRE) were detected by automatic biochemical analyzer. RESULTS: The lung organ coefficients of rats in the TET group were lower than those of the model group on the 28 th and 56 th days(all P<0.05). The lung organ coefficient of the rats in the TET group on the 56 th day was higher than that in the same group on the 28 th day(P<0.05). The lung tissue structure of the control group was normal. After modeling, the lung tissues of rats in model group showed different degrees of pathological changes such as alveolar structure destruction, inflammatory cell infiltration, and fibrosis on the 28 th and 56 th days. The degree of pathological changes in TET group was less than that of the model group. In the lung tissues of rats in the model group, the levels of TNF-α, TGF-β1, IL-1β and IL-6 were higher than those of the control group(all P<0.01). The levels of TNF-α, TGF-β1, IL-1β and IL-6 in the lung tissues of rats in the TET group were lower than that of the model group(all P<0.01), but there was no statistically significant difference when compared with the control group(all P>0.05). The activities of ALT and AST in the TET group were higher than those in the model group and the control group(all P<0.01). The level of serum BUN in TET group was higher than that in control group(P<0.01), but it showed no statistical difference when compared with the control group(P>0.05). The level of serum CRE in each group showed no significant difference(P>0.05). There were no abnormal pathological changes found in the liver and kidney tissues of rats in each group at different times. CONCLUSION: TET can reduce the inflammatory response in silicosis rats and improve lung tissue fibrosis; however, the therapeutic dose may have certain toxicity to the liver and kidney of the silicosis rats.

Identification of Gastrodiae Rhizoma chromatographic peaks identification by liner calibration with two reference substances assisted / 药学学报

This study aimed to establish a method for positioning six chromatographic peaks occurred in HPLC profile of Gastrodiae Rhizoma. The "liner calibration with two reference substances" (LCTRS) method was used to calculate the retention time so as to assist in positioning of chromatographic peaks in terms of the prediction accuracy of retention time and the coincidence rate of chromatographic column. A total of 24 C18 chromatographic columns from different brands and types available were used to determine the retention times of six components in Gastrodiae Rhizoma, then the average retention time of each component was obtained as standard retention time (SRT). Parishin E (peak 3) and Parishin A (peak 6) were simultaneously taken as reference substance to forecast the retention time of the other four components by using the LCTRS method. Four different C18 columns were employed to verify the method. Meanwhile, for the purpose of comparison, the relative retention time (RRT) method was applied to forecast the retention time, by using Parishin E as the single reference substance. The comparison between LCTRS and RRT methods indicated that the former was more accurate in predicting the retention time and more applicable in utilization of chromatographic columns. This study demonstrated that the LCTRS method shows the superior performance in positioning of chromatographic peak, and therefore has a good prospect of application.

Application of environmentally sensitive hydrogels in drug delivery / 药学学报

Environmentally sensitive hydrogels are a novel formulation that has developed rapidly in recent years. It could form semi-solid with good adhesion in the topical sites based on different physiological environments. Its long local retention time is conducive for sustained drug release, and the preparation process is relatively simple and easy to realize industrialization. This review summarized the categories, commonly used polymer, and different administration routes based on the recently published literatures. According to different response factors, it can be divided into temperature, pH, ion, light, and multiple sensitive hydrogels, among which temperature-sensitive hydrogels are the most common. The most commonly used polymers include chitosan, poly N-isopropyl acrylamide, and poloxamer. There are different administration routes for environmentally sensitive hydrogels, such as transdermal, ophthalmic, nasal, oral, vaginal, rectal, injection, etc. Environmentally sensitive hydrogels have broad prospects in clinical application.

The combined therapeutic effects of 5-aminolevulinic acid cubic liquid crystal and light needles for basal cell cancer / 药学学报

The article was to study the effect of local photodynamics therapy combined with carbon dioxide lattice laser - "light needles" for the treatment of basal cell carcinoma (BCC). 5-Aminolevulinic acid (5-ALA) cubic liquid crystal using glyceryl monostearate (GMO) as the substrate was prepared. The cytotoxicity of 5-ALA cubic liquid crystal combined with light needles in vitro were evaluated. The pharmacodynamics study of 5-ALA cubic liquid crystal combined with light needles of high or low energy for BCC was carried out based on the pathological changes, tumor volume, vascular endothelial growth factor (VEGF) expression and the recurrence rate, which has been approved by the Ethics Committee of Beijing Institute of Radiation Medicine. The cubic liquid crystal was isotropic with the lattice of PN3M. The cytotoxicity of 5-ALA cubic liquid crystal combined with light needles was much higher than that of 5-ALA or light needles alone. Compared with light needles or photodynamic therapy alone, 5-ALA cubic liquid crystal combined with light needles of high energy could prevent the BCC metastasis and of low energy could inhibit BCC growth. It demonstrated the obvious therapeutical effects for BCC. 5-ALA cubic liquid crystal combined with light needles can effectively treat BCC, which provides a new choice for clinical BCC treatment.

Hetero-biosynthesis of the main bioactive components from medicinal fungus Shiraia bambusiccola / 药学学报

italic>Shiraia bambusiccola is an important medicinal fungus in China. Hypocrellins with perylenequinone skeleton are main bioactive components of Shiraia bambusiccola, which are widely used in food, medicine, pesticide and other fields as natural photosensitizers. For example, "hypocrellin ointment" has already been used clinically. As a rare and vulnerable species, wild Shiraia bambusiccola resources are very limited. Due to the complex structure and chanllenge in chemical total synthesis of hypocrellins, it is urgent to find an effective strategy to rationally utilize its medicinal value while protecting the wild resources. In this study, a candidate gene cluster hpc was identified in Shiraia sp. cfcc 84681 based on careful bioinformatic analysis. A heterologous expression system for hpc gene cluster was successfully constructed and a mutant strain with high yield of hypocrellins was obtained, which mainly produced hypocrellin A and isohypocrellin A. The main ingredients in the mutant strain are consistent with that in the wild Shiraia bambusiccola. These results provide a new strategy to solve the shortage of wild Shiraia bambusiccola resources.

Effect of 5-aminoimidazole-4-formamide Ribonucleotide Combined with Interferon on Chronic Myeloid Leukemia K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To study the effect of 5-aminoimidazole-4-formamide ribonucleotide (AICAR) combined with interferon (IFN-α-2b) on the proliferation and apoptosis of chronic myeloid leukemia K562 cells, and explore its possible mechanism.@*METHODS@#CCK-8 method was used to detect the inhibition of cell proliferation. Wright Giemsa method was used to stain and cell morphology was observed by light microscopy. FITC Annexin V/PI double staining method was used to analyze the change of apoptosis rate. Immunocytochemistry method was used to detect the expression of wild-type P53 protein.@*RESULTS@#Different concentration of AICAR was inhibitory effect on K562 cells at different time point of action for 24 h, 48 h, and 72 h, and the inhibition was time and dose-dependent (r=0.71, r=0.84). The combination of AICAR and IFN-α-2b could effectively inhibit the proliferation and promote apoptosis of K562 cells. The inhibition rate of K562 cells was (45.26±2.54)%, and the early apoptosis rate was (33.72±0.23)%, which was statistically significantly different from the control group, AICAR or IFN-ɑ-2b alone (P<0.05). The combination of two drugs promoted the expression of wild-type p53 protein.@*CONCLUSION@#AICAR and/or IFN-ɑ-2b can inhibit the cell proliferation and promote the apoptosis of K562 cells. The combination of two drugs shows synergistic antitumor effect, and its mechanism may be related to the promotion of high expression of wild-type p53 protein.

Effect of electroacupuncture at Wnt/β-catenin signaling pathway on inhibiting cartilage degeneration in rats with knee osteoarthritis / 中国针灸

OBJECTIVE@#To explore the action mechanism of electroacupuncture (EA) for knee osteoarthritis (KOA) based on Wnt/beta-catenin (Wnt/β-catenin) signaling pathway.@*METHODS@#Ten rats were randomly selected into a sham-operation group among 50 male 2-month-old SD rats, and the KOA model was established in the remaining 40 rats by modified Hulth method. Four weeks after the model establishment, the rats were randomly divided into a model group, an experimental A group, an experimental B group and an experimental C group, 10 rats in each group. The rats in the sham-operation group and model group did not receive any intervention. The rats in the experimental A group were treated with EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) for 15 min. The rats in the experimental B group were treated with EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) for 30 min. The rats in the experimental C group were treated with EA at non-acupoint for 15 min. EA intervention was given once a day, five times a week, and totally 12-week treatment was given. After 12 weeks, the knee cartilage tissues were stained and the morphological changes were observed under light microscopy; the severity of cartilage degeneration was evaluated by modified Mankin's score; the content of interleukin-1β (IL-1β) in synovium tissues was detected by ELISA method; the content of Wnt-4, β-catenin and matrix metalloprotein-13 (MMP-13) in cartilage tissues was detected by Western blot method.@*RESULTS@#Compared with the sham-operation group, in the model group the morphology and structure of cartilage were disordered, the number of cells was significantly reduced, the matrix was decontaminated and tidal line was incomplete; the Mankin's score was significantly increased (0.05).@*CONCLUSION@#EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) may reduce the expression of MMP-13 and the production of inflammatory factor IL-1β through Wnt/β-catenin signaling pathway, thus inhibit the degradation of cartilage matrix and the apoptosis of chondrocyte, and improve the morphology and structure of cartilage.