Efficacy analysis of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

Fipronil and its metabolites in indoor dust in Shenzhen in 2020 -2021: analysis of residual levels and temporal variations / 公共卫生与预防医学

Objective To explore the residual level of FPMs in indoor dust samples in Shenzhen from 2020 and 2021, and to analyze its temporal distribution characteristics. Methods In the present study, indoor dust samples (n=193) from residential buildings in Shenzhen. were collected to analyze the temporal variation characteristics of FPMs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to determine the concentrations of FP and its four major metabolites (fipronil-sulfone, fipronil-sulfide, fipronil-desulfinyl, and fipronil-amide; abbreviated as FP-SFO, FP-SFI, FP-DES, and FP-AM) in the samples. The sum of the concentrations of FP and its four metabolites was represented as additive mass concentration (ΣFPMs). Additionaly, Wilcoxon test was performed to determine the temporal distribution differences of FPMs’ concentrations. Results From 2020 to 2021, the concentration of ΣFPMs for the in door dust samples in Shenzhen ranged from 0.51 to 4 415 ng/g (median: 18.8ng/g). FP, FP-SFO AND FP-SFI were the major target analytes in the sample with detection rates of 90.60%，86.20% and 75.40%, respectively. The detection rates of other metabolites were low (≤ 44.3%). Analysis of the temporal variation trend of FPMs’ concentrations showed that there was no significant difference in the levels of ΣFPMs between warm season（spring and summer）and cold season（autumn and winter）in the indoor dust samples from 2020 to 2021(2.38 vs 2.84ng/g , P > 0.05). However , the concentrations of FP-SFI and ΣFPMs in the indoor dust samples collected from 2021 showed an significantly increasing trend compared with 2020（1.02 vs 1.89 , 17.80vs. 20.10 ng/g , P < 0.05). Conclusion From 2020 to 2021 , the detection level of FPMs in indoor dust in Shenzhen is relatively high and shows an upward trend , with no obvious seasonal difference. However, whether the residual level of FPMs in indoor dust poses a risk to human health needs further study.

Analysis of the core knowledge level of chronic diseases in Chinese adults and related factors / 中华预防医学杂志

Objective: To understand the core knowledge level and influencing factors of chronic disease prevention and control in Adults in China, and to provide a scientific basis for formulating chronic disease prevention and control measures. Methods: In this study, cross-sectional survey and quota sampling were used to recruit 173 819 permanent residents aged 18 and above from 302 counties of adult chronic diseases and nutrition surveillance in China to conduct an online questionnaire survey, including basic information and core knowledge of chronic diseases. The scores of the core knowledge of chronic disease prevention and control were described by median and interquartile range, the Wilcoxon rank sum test or the Kruskal Wallis test was used for the inter-group comparison, and the correlation factors of the total score were analyzed by the multilinear regression model. Results: A total of 172 808 participants were surveyed in 302 counties and districts, of which 42.60%(73 623) were male and 57.40%(99 185) were female; The proportion of respondents aged 18-44, 45-59, and 60 years old and above was 54.74% (94 594), 30.91% (53 423) and 14.35% (24 791), respectively. The total score of the core knowledge of chronic prevention and control in the total population was 66(13), and the scores of different characteristic groups were different, and the differences were statistically significant: the eastern region had the highest score at 67(11) (H=840.66, P<0.01), the urban 66(12) was higher than the rural 65(14) (Z=-31.35, P<0.01), and the male 66(14) was lower than female 66(12) (Z=-11.66, P<0.01), 18-24 years old 64(13) was lower than other age groups(H=115.80, P<0.01), and undergraduate degree and above had the highest score compared to other academic qualifications, with 68(9) points(H=2 547.25, P<0.01). Multivariate analysis showed that eastern (t=27.42, P<0.01), central (t=17.33, P<0.01), urban (t=5.69, P<0.01), female (t=17.81, P<0.01), high age (t=46.04, P<0.01) and high education (t=57.77, P<0.01) had higher scores of core knowledge of chronic disease prevention and control than other groups, the scores of core knowledge of chronic disease prevention and control of professional and technical personnel (t=8.63, P<0.01), state enterprises and institutions (t=38.67, P<0.01), agriculture, forestry, animal husbandry, fishery and water conservancy production (t=5.30, P<0.01), production, transportation and commercial personnel (t=24.87, P<0.01), and other workers (t=8.89, P<0.01) were higher than those of non-employed people. Conclusion: There are differences in the total scores of the core knowledge of chronic disease prevention and control in different characteristics of people in China, and in the future, health education on the prevention and treatment of chronic diseases should be strengthened for specific groups to improve the knowledge level of residents.

Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis.@*METHODS@#Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase.@*RESULTS@#The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05).@*CONCLUSIONS@#Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*METHODS@#The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed.@*RESULTS@#All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity.@*CONCLUSIONS@#The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Cross-sectional study of low anterior resection syndrome in patients who have survived more than 5 years after sphincter-preserving surgery for rectal cancer / 中华胃肠外科杂志

Objective: In this study, we aimed to investigate the prevalence of low anterior resection syndrome (LARS) in patients who had survived for more than 5 years after sphincter-preserving surgery for rectal cancer and to analyze its relationship with postoperative time. Methods: This was a single-center, retrospective, cross-sectional study. The study cohort comprised patients who had survived for at least 5 years (60 months) after undergoing sphincter- preserving radical resection of pathologically diagnosed rectal adenocarcinoma within 15 cm of the anal verge in the Department of Gastrointestinal Surgery, Peking University People's Hospital from January 2005 to May 2016. Patients who had undergone local resection, had permanent stomas, recurrent intestinal infection, local recurrence, history of previous anorectal surgery, or long- term preoperative defecation disorders were excluded. A LARS questionnaire was administered by telephone interview, points being allocated for incontinence for flatus (0-7 points), incontinence for liquid stools (0-3 points), frequency of bowel movements (0-5 points), clustering of stools (0-11 points), and urgency (0-16 points). The patients were allocated to three groups based on these scores: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The prevalence of LARS and major LARS in patients who had survived more than 5 years after surgery, correlation between postoperative time and LARS score, and whether postoperative time was a risk factor for major LARS and LARS symptoms were analyzed. Results: The median follow-up time of the 160 patients who completed the telephone interview was 97 (60-193) months; 81 (50.6%) of them had LARS, comprising 34 (21.3%) with minor LARS and 47 (29.4%) with major LARS. Spearman correlation analysis showed no significant correlation between LARS score and postoperative time (correlation coefficient α=-0.016, P=0.832). Multivariate analysis identified anastomotic height (RR=0.850, P=0.022) and radiotherapy (RR=5.760, P<0.001) as independent risk factors for major LARS; whereas the postoperative time was not a significant risk factor (RR=1.003, P=0.598). The postoperative time was also not associated with LARS score rank and frequency of bowel movements, clustering, or urgency (P>0.05). However, the rates of incontinence for flatus (3/31, P=0.003) and incontinence for liquid stools (8/31, P=0.005) were lower in patients who had survived more than 10 years after surgery. Conclusions: Patients with rectal cancer who have survived more than 5 years after sphincter-preserving surgery still have a high prevalence of LARS. We found no evidence of major LARS symptoms resolving over time.

Correlation between pelvic relapses of rectal cancer after radical and R0 resection: A regression model-based analysis / 中华胃肠外科杂志

Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.

Inhibition of pyrrolidine dithiocarbamate on transforming growth factor-beta 2 induced epithelial-mesenchymal transition in human lens epithelial cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the mechanism of pyrrolidine dithiocarbamate(PDTC)on transforming growth factor-beta 2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(LECs).METHODS: LECs were treated with various doses of PDTC chemicals following TGF-β2 caused EMT on these cells. Cell proliferation and lateral migration were discovered using the CCK-8 and cell scratch test. The markers of EMT, including E-cadherin, α-SMA and nuclear factor-κB(NF-κB)signaling pathway-related expression, were tested by Western Blot as well as the changes in the expression of the apoptosis-related proteins BAX, BCL-2, Caspase-3, and Cyclin D1.RESULTS: The proliferation and migration viability of cells in the TGF-β2 treated group was increased compared to the group without TGF-β2, and the expression of α-SMA increased whereas the E-cadherin expression decreased. With the effect of TGF-β2, NF-κB p65 and phosphorylated NF-κB p65 expression increased, the concentration of TGF-β2 that had the greatest capacity for proliferation and migration was 10 ng/mL(P&#x003C;0.05). Mechanism study of PDTC-induced EMT reversal and apoptosis showed that cell viability and migratory capability were both significantly reduced after PDTC intervention; PDTC prevents IκB phosphorylation, thus inhibiting NF-κB nuclear translocation. Protein associated to the NF-κB signaling pathway, and protein expression of NF-κB/IκBα/p-IκBα/Iκκ-α/p-Iκκ-α was decreased(P&#x003C;0.05), PDTC increased the expression of the pro-apoptotic protein BAX/Caspase-3, expression of the inhibitor of apoptosis protein BCL-2 and the cell cycle protein Cyclin D1 was reduced. The expression of NF-κB/IκB mRNA was reduced, expression of the apoptosis-related mRNA BAX increased, while BCL-2 reduced.CONCLUSION: The EMT in LECs cells induced by TGF-β2 can be significantly reversed by PDTC, which may be related to the decreased expression of NF-κB p65/IκB/Iκκ-α and activation of apoptosis-related protein. PDTC can reverse EMT by inhibiting NF-κB signaling pathway and induce apoptosis of abnormally proliferated cells, which will provide new potential therapeutic agents for posterior capsular opacification(PCO)treatment.

Reflection on the regulatory path for online sales of Chinese medicinal materials in the context of live streaming / 中国药房

OBJECTIVE To provide feasible regulatory paths for the online sales supervision of Chinese medicinal materials from the perspective of the characteristics of new online sales and the characteristics of Chinese medicinal materials. METHODS Through the investigation of the sales form of Chinese medicinal materials on the e-commerce platform and the search of Chinese medicinal materials online dispute cases， the difficulties and existing problems in the supervision of Chinese medicinal materials under the new online sales model were analyzed， and corresponding countermeasures were proposed. RESULTS & CONCLUSIONS Clarifying the conceptual boundary between Chinese medicinal materials and their decoction pieces， agricultural products and food is the key to standardizing the online sale of Chinese medicinal materials. The regulatory criteria， which determine whether Chinese medicinal materials belong to drug management based on whether they had been included in medicinal channels， didn’t consider the diversity of online sales channels for Chinese medicinal materials， their safety and the disguised sales of Chinese herbal decoction pieces. It is necessary to establish the concept of hierarchical management of Chinese medicinal materials， strictly restrict the behavior of claiming the efficacy of Chinese medicinal materials and selling Chinese herbal decoction pieces in live streaming， improve the defining path of false propaganda of Chinese medicinal materials， implement the responsibilities and obligations of live streaming marketing subjects and platforms， and safeguard the legitimate rights of consumers.

Research progress of Cryptococcus gattii meningitis with different immune status / 中华神经科杂志

Cryptococcus gattii is a kind of Cryptococcus that infects the lungs and central nervous system through the inhalation of infectious particles such as spores or Cryptococcus yeast cells. The development of clinical disease of Cryptococcus gattii may be determined by the sex, immunity and genetics of the host factors, in which immune system factors play an important role in host injury. Their defects will have serious clinical consequences. Cryptococcus gattii mainly infects the population with normal immune, and the infection of immunosuppressed population is rare. The infection mechanism, molecular types, clinical characteristics, treatment and prognosis of Cryptococcus gattii meningitis were different between the two populations. This article reviews the main differences in different immune status with Cryptococcus gattii meningitis.

Influence of different sphincter-preserving surgeries on postoperative defecation function / 中华胃肠外科杂志

Advances in surgical techniques and treatment concept have allowed more patients with low rectal cancer to preserve sphincter without sacrificing survival benefit. However, postoperative dysfunctions such as fecal incontinence, frequency, urgency, and clustering often occur in patients with low rectal cancer. The main surgical procedures for low rectal cancer include low anterior rectum resection (LAR), intersphincteric resection (ISR), coloanal anastomosis (Parks) and so on. The incidence of major LARS after LAR is up to 84.6%. The postoperative function of ISR is even worse than LAR. Moreover, the greater the extent of resection ISR surgery, the worse the postoperative function. There are few studies on the function of Parks procedure. Current evidence suggests that the short-term function of Parks procedure is inferior to LAR, but function can gradually recovered over time. Colorectal surgeons have attempted to improve postoperative defecation by modifying bowel reconstructions. Current evidence suggests that J pouch or end-to-side anastomosis during LAR does not reduce the incidence of defecation disorders. Pouch reconstruction during ISR cannot reduce the incidence of severe LARS either. In general, the protection of postoperative defecation function in patients with low rectal cancer still has a long way to go.

Observation of PD-1+CXCR5+CD4+T lymphocyte and sPD-1 levels in HBeAg positive chronic hepatitis B virus carriers treated with entecavir / 中华肝脏病杂志

Objective: To dynamically observe the clinical efficacy of entecavir and the changes of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. Methods: There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1+CXCR5+CD4+T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. Results: At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1+CXCR5+CD4+T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (F=16.65, P<0.05). There was no significant difference between group A and group C (P>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (F=10.95, P<0.05). There was no significant difference between group A and group C (P>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (P>0.05), but were significantly higher than group B (P<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (P<0.05). <0.05), but group A was significantly higher than group B (P<0.05), and there was no significant difference between group A and group C (P>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (P<0.05), and there was no significant difference between group A and group B (P>0.05). Peripheral blood PD-1+CXCR5+CD4+T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (P<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (P<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1+CXCR5+CD4+T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (r=0.376, P<0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (r=0.598 and 0.384, P<0.05). In group B at 48 weeks, the decreased levels of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (P<0.05). Conclusion: Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1+CXCR5+CD4+T lymphocytes.

Prognostic study and influencing factors analysis for the dynamic changes of serum FT3, FT4 and TSH levels in patients with hemorrhagic stroke under 45 years of age / 公共卫生与预防医学

Objective To discuss the epidemiological characteristics of the dynamic changes of serum FT3, FT4, and TSH levels in patients with hemorrhagic stroke under the age of 45, and to discuss the prognostic evaluation effects and influencing factors of these indicators. Methods From January 2017 to January 2020, 227 patients with multicenter hemorrhagic stroke in our hospital were selected for analysis. Collect and analyze prognosis (death, rebleeding, no adverse prognosis) at baseline and 12 months of follow-up; monitor serum FT3, FT4, and TSH levels during treatment at the same time during follow-up, 7 days after treatment, and 14 days after treatment. Observe the trend characteristics of dynamic changes. The assay method is enzyme-linked immunosorbent assay. At the end of the follow-up, the subjects were divided into three groups: death, rebleeding, and no adverse prognosis according to the prognostic outcome of the 12-month short-term follow-up. The epidemiological characteristics of patients with different prognosis and the dynamic change trend of FT3, FT4 and TSH in the same serum were compared. The interconnectedness. Results There were no statistically significant differences in gender and age between the three groups (P>0.05), but the differences in hypertension, hyperglycemia, and hyperlipidemia were statistically significant (P0.05). The FT4 level of the case group was significantly higher than that of the control group at all times (P0.05). The TSH level of the case group was significantly higher than that of the control group at all times (P0.05). With the decrease of the patient's age, the serum FT3 level has a gradually increasing trend, and the serum FT4, TSH level, mortality and rebleeding rate have a gradually decreasing trend (P<0.05). Conclusion The continuous decrease of FT3 level and the continuous increase of FT4 and TSH levels are potentially associated with the poor prognosis of patients with hemorrhagic stroke, which is worthy of clinical attention.

Genetic Analysis and Prenatal Diagnosis of Thalassemia in Couples of Childbearing Age in Quanzhou Region Fujian Province, China / 中国实验血液学杂志

OBJECTIVE@#To explore the genotypes and prenatal diagnosis of thalassemia in couples of childbearing age in Quanzhou, Fujian Province.@*METHODS@#Blood routine and hemoglobin electrophoresis were performed for initial thalassemia screening in 76 328 couples in Quanzhou region from July 2017 to July 2020. The couples with positive initial screening results further underwent thalassemia gene test. Couples carrying homotypic thalassemia genes underwent prenatal diagnosis in the second trimester.@*RESULTS@#Among 76 328 couples of childbearing age, 1 809 couples of positive initial thalassemia screening were identified, with the positive rate about 2.37%. Further results of genetic detection of the 1 809 couples showed that 985 cases were diagnosed as α- thalassemia, of which --sea/αα was the most frequency, followed by -α3.7/αα and ααQS/αα; 296 cases were diagnosed as β-thalassemia, the most frequency mutations were 654M/N and 41-42M/N; 26 cases of compound α and β-thalassemia were detected. In addition, 3 rare cases of thalassemia were detected, including --THAI/αα, SEA-HPFH, and -α6.9/--sea. Among them, 108 couples were confirmed as homologous thalassemia, with the detection rate about 5.97%, including 96 couples of homologous α-thalassemia, 9 couples of homologous β-thalassemia, and 3 couples with one had compound α- and β-thalassemia. Among them, 17 couples with homologous α-thalassemia underwent prenatal diagnosis in the second trimester, of which 1 case of Hb Bart's Hydrops Syndrome, 3 cases of HbH disease, 9 cases of silent thalassemia or α-thalassemia minor, and 4 cases of healthy fetuses were detected. Fetal chromosome karyotype analysis showed that 16 cases were normal and 1 case diagnosed as Down syndrome.@*CONCLUSION@#Thalassemia screening in pre-marital and pre-pregnancy, and prenatal diagnosis can effectively reduce the birth of children with thalassemia intermediate and thalassemia major. It is necessary to perform chromosome karyotype analysis at the same time as prenatal diagnosis of thalassemia gene in order to avoid fetus with abnormal chromosome.

The Factors Affecting Relapse in Pediatric B-cell Acute Lymphoblastic Leukemia Patients without Prognostic Fusion Genes Following Up for 10 years / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients.@*METHODS@#B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients.@*RESULTS@#There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients.@*CONCLUSION@#Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.

Co-amorphous technology to improve dissolution and physical stability of silybin / 中国中药杂志

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.

Control strategy for the limit of aldehydes in polysorbates based on genotoxicity and influence on the aggregation of monoclonal antibody / 中国药科大学学报

@#An HPLC pre-column derivatization detection method was established to detect and analyze the formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 from different manufacturers.The effects of aldehyde and acetaldehyde on the aggregation of adalimumab under different conditions were monitored.Based on the control of genotoxic impurities and the influence on the stability of monoclonal antibody preparations, the control limits of the two chemicals were preliminarily obtained.2, 4-dinitrophenylhydrazine (2, 4-DNPH) was applied as the derivatization reagent in HPLC pre-column derivatization; acetonitrile and water were used as mobile phase to perform a gradient elution on a C8 (4.6 mm × 150 mm, 5 μm) chromatographic column.The detection wavelength was 360 nm, and the external standard method was used for quantification.Verification results showed that the method was suitable for the quantitative analysis of trace formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 . The detection and analysis of formaldehyde or acetaldehyde in different batches of polysorbate 80 and polysorbate 20 from different manufacturers showed that the content of formaldehyde and acetaldehyde were quite different. The content of formaldehyde and acetaldehyde in polysorbate 80 were significantly higher than those of polysorbate 20. After monitoring the changes of adalimumab aggregates treated by formaldehyde and acetaldehyde by size exclusion chromatography (SEC), it was found that the effect of formaldehyde on adalimumab aggregation was significantly higher than that of acetaldehyde.According to the requirements of ICH M7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk), the impurity limits of formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 for monoclonal antibody preparations were calculated from the perspective of risk assessment.Combined with the influence on the aggregation stability of monoclonal antibodies, the preliminary limis for acetaldehyde and acetaldehyde were recommended to be ≤ 7 μg/g and ≤ 765 μg/g, respectively.

Research progress of colorectal surgery in 2021 and future prospects / 中华胃肠外科杂志

In recent years, with the wide application of immune score and liquid biopsy to guide the accurate diagnosis and precise treatment of colorectal cancer, colorectal surgery develops more rationally and scientifically. The strategy of organ function protection in colorectal surgery gradually attracts more and more attention. The continuous development of comprehensive treatments, such as targeted therapy and immunotherapy, provides more choices for colorectal cancer patients. Several significant progress in surgical strategies for benign colorectal diseases challenges the traditional concepts as well. The advances in medical science and the innovation of concepts and ideas set high new standards for the development of colorectal surgery in China. Efforts are required to improve the standardization of diagnosis and treatment of colorectal disease. There is still a long way to go to explore patient-centered new technologies, new concepts and new fields of accurate diagnosis and precise treatment in colorectal surgery.

Research progress of sexual dysfunction following rectal cancer surgery / 中华胃肠外科杂志

Sexual dysfunction with the incidence of 5%-90% is a common postoperative complication of rectal cancer and the ratio of men and women is similar. Sexual function is innervated by the abdominal-pelvic autonomic nerve. Different sexual dysfunctions can be caused by different parts and degrees of injury in autonomic nerve during operations of rectal cancer. With the development of pelvic autonomic nerves preservation in rectal cancer radical resection, postoperative sexual function can be protected. There may be many factors increasing the incidence of postoperative sexual dysfunction in rectal cancer, such as postoperative psychological factors, stoma, abdominal-perineal resection and radiotherapy. The effects of laparoscopic surgery, robotic surgery, transanal total mesorectal excision and lateral lymph node dissection on postoperative sexual function remain controversial. Based on the multidisciplinary cooperation model, attention should be paid to psychological intervention of patients and their partners. In clinical practice, for male using phosphodiesterase-5 inhibitors, vacuum erectile devices, injection of vasodilators through the penis or urethra, and for female local application of estrogen and lubricants in the vagina are effective treatment for postoperative sexual dysfunction of rectal cancer. In addition, stem cell therapy has a promising prospect for sexual dysfunction.