Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

Objective To understand the correlation between atmospheric particulate matter and confirmed cases of influenza in Pudong New Area, Shanghai, and to provide a basis for formulating relevant control measures. Methods The meteorological factors (average temperature, relative humidity, and atmospheric pressure), atmospheric pollutants (PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃) and confirmed cases of influenza of different ages and genders from January 1, 2014 to December 31, 2018 were collected. Data was fitted to a generalized additive model of Poisson distribution to assess the correlation between atmospheric particulate matter (PM_2.5, PM₁₀) and the number of confirmed cases of influenza. Results There was a correlation between atmospheric particulate matter and the number of confirmed cases of influenza in Pudong New Area. For each increase of 10 μg/m³ in the concentration of the two types of particulate matter, the confirmed cases increased by 0.638% (95%CI: 0.413%~0.864%), and 0.520% (95%CI: 0.324%~0.715%), respectively, when the lag was 0-7d (lag07). People of different ages and genders were affected by atmospheric particulate matter differently. After incorporating the effects of SO₂, NO₂, CO, and O₃ in the multi-pollutant model, the effect of atmospheric particulate matter on the number of influenza cases had changed. Conclusion The increase of atmospheric particulate matter (PM_2.5, PM₁₀) concentration increased the number of confirmed cases of influenza in Pudong New Area.

Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C. difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .

Objective:To explore the application effect of traditional Chinese medicine iontophoresis in patients with diabetic peripheral neuropathy (DPN) of Qi deficiency and blood stasis type.Methods:Using the convenient sampling method, a total of 72 patients with DPN of Qi deficiency and blood stasis type who were admitted to Department of Endocrinology of Pudong New Area Hospital of Traditional Chinese Medicine in Shanghai from January to June 2019 were selected as the research objects. According to the random number table method, 72 patients with DPN of Qi deficiency and blood stasis were randomly divided into the experimental group and the control group, with 36 cases in each group. Patients in the control group were given conventional treatment and health education. On this basis, patients in the experimental group were given traditional Chinese medicine iontophoresis at Zusanli and Sanyinjiao points on both sides for 14 days of intervention. Visual Analogue Scale (VAS) , Toronto Clinical Scoring System (TCSS) and Pittsburgh Sleep Quality Index (PSQI) were used to compare the limb pain, neural symptoms and sleep quality of the two groups before and after intervention.Results:Finally, 34 patients in the experimental group and 35 patients in the control group completed the study. After the intervention, VAS scores of the two groups were lower than those before the intervention and that of the experimental group was lower than that of the control group, and the differences were all statistically significant ( P<0.05) . After the intervention, the total scores of TCSS, sensory function scores and neural symptoms scores of the two groups decreased compared with those before the intervention, and those of the experimental group were lower than those of the control group, and the differences were all statistically significant ( P<0.05) . After the intervention, PSQI of the two groups decreased, and that of the experimental group was lower than that of the control group, and the differences were all statistically significant ( P<0.05) . Conclusions:Traditional Chinese medicine iontophoresis can alleviate the limb pain of patients with DPN of Qi deficiency and blood stasis, improve the sensory function, neural symptoms and TCSS score of them and improve sleep problems caused by limb pain.

At present, researches on self-management of patients with multiple chronic conditions (MCC) are increasing in foreign countries, but there are still few reports about it in China. This paper introduces research progress on self-management of MCC patients from three aspects including self-management status of MCC patients, influencing factors and measurement tools so as to provide ideas for researches on the self-management of MCC patients in China.

Objective To evaluate the clinical value of Fluorine-18-fluorodeoxyglucose (18F-FDG) positron-emission temography-computed tomography (PET-CT) examination in intrahepatic cholangiocarcinoma (ICC) staging.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 190 patients with ICC who were admitted to the Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Military Medical University from September 2013 to June 2016 were collected.There were 107 males and 83 females,aged from 37 to 79 years,with an average age of 57 years.There were 90 cases without distant metastasis undergoing surgery treatment and 100 with distant metastasis undergoing non-surgical treatment.Patients underwent preoperative CT,magnetic resonance imaging (MRI),and PET-CT examination,and then received surgery or non-surgery according to preference of patients and their family members.Observation indicators:(1) imaging features on preoperative CT,MRI,PET-CT examination;(2) treatment;(3) evaluation of tumor diameter,multiple tumors,macrovascular invasion,and bile duct invasion by three examinations in ICC staging of patients undergoing operation;(4) evaluation of regional lymph node metastasis by three tests in ICC staging of patients undergoing operation;(5) evaluation of distant metastasis in ICC staging by three tests.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed by single factor ANOVA and paired comparison was analyzed by SNK method.Measurement data with skewed distribution were described as M (range).Count data were described as absolute number or percentage,and comparison between groups was analyzed using the chi square test.Results (1) Imaging features on preoperative CT,MRI,PET-CT examination:all the 190 patients received routine upper abdominal CT,MRI,and systemic PET-CT examination before treatment.CT imaging of ICC showed inhomogeneous low density on plain scan,peripheral enhancement in arterial phase,persistent enhancement of tumor margin in portal phase,and sometimes mild to moderate centripetal enhancement.MRI imaging showed heterogeneous low signal on T1-weighted imaging,uneven high,and slightly high signal on T2-weighted imaging.Reinforcement on MRI is the same as CT.Transverse images,fusion transverse images and maximum intensity projection images of PET-CT imaging showed abnormal high FDG uptake around the tumor.(2) Treatment:81 out of the 90 ICC patients with surgery treatment underwent hepatectomy and lymphadenectomy,and 9 underwent only tumor tissue biopsy and lymph node biopsy due to intraoperative finding of abdominal metastasis.Of the 100 non-operated patients,30 received systemic chemotherapy,23 received local radiotherapy,and 47 gave up treatment.(3) Evaluation of tumor diameter,multiple tumors,macrovascular invasion,and bile duct invasion by three examinations in ICC staging of patients undergoing operation:the tumor diameters of ICC on CT,MRI and PET-CT were (6.8±2.8)cm,(6.9±2.9)cm,(7.2±2.8)cm,respectively.There was no significant difference among the three methods (F=0.085,P＞0.05).CT,MRI,PET-CT had similar accuracy of 80.0％ (72/90),78.9％ (71/90),72.2％ (65/90) on diagnosing multiple tumors,87.8％(79/90),92.2％ (83/90),94.4％ (85/90) for macrovascular invasion,and 93.3％ (84/90),95.6％ (86/90),96.7％ (87/90) for vascular and bile duct invasion,respectively,there was no significant difference in the above indicators between the three groups (x2 =1.801,2.662,1.131,P＞0.05).(4) Evaluation of regional lymph node metastasis by three examinations in ICC staging of patients undergoing operation:the accuracy of CT,MRI and PET-CT examination for lymph node metastasis was 62.2％ (56/90),68.9％(62/90),86.7％ (78/90) and sensitivity was 40.0％ (16/40),47.5％ (19/40),80.0％ (32/40),respectively,showing significant differences between the three groups (x2 =14.446,14.666,P＜0.05),showing a significant difference between CT and PET-CT examination (x2=14.134,13.333,P＜0.05),showing a significant difference between MRI and PET-CT examination (x2=8.229,9.141,P＜0.05).The sensitivity of CT,MRI and PET-CT examination for lymph node metastasis was 80.0％ (40/50),86.0％ (43/50),92.0％ (46/50),showing no significant difference between the three groups (x2=2.990,P＞0.05).(5) Evaluation of distant metastasis in ICC staging by three tests:there were 27,34 and 100 cases with distant metastasis evaluated by CT,MRI and PET-CT examination,including 40 with supraclavicular lymph node metastasis,32 with bone metastasis,30 with mediastinal lymph node metastasis,20 with hilar lymph node metastasis,17 with pulmonary metastasis;77 patients had more than 2 sites of metastasis.The accuracy of CT,MRI and PET-CT examination for distal metastasis in 190 ICC patients was 61.58％ (117/190),65.26％ (124/190),98.42％ (187/190),respectively,with a significant difference between the three groups (x2=83.639,P＜0.05),with a significant difference between CT and PET-CT examination (x2=80.592,P＜0.05),between MRI and PET-CT examination (x2=70.284,P＜ 0.05).Conclusion PET-CT examination makes up for the deficiency of CT and MRI in judging regional lymph node metastasis and distant metastasis,and contributes to the clinical staging of ICC.

Tet2 (member 2 of the Tet family) plays an important role in DNA demethylation modification, epigenetic regulation, and hematopoiesis. In our previous study, we found that Tet2 knockout mice progressively developed lymphocytic leukemia and myeloid leukemia with aging. However，the role of Tet2 in bone marrow microenvironment is unclear. Here in this study, we found that more Tet2-/- mesenchymal stem cells (MSCs) from bone marrow were in the G2/M cell cycle stages. The division time of Tet2-/- MSCs was shorter than that of the control cells. The growth rate of Tet2-/- MSCs was accelerated. The cobblestone area-forming cells assay (CAFC) showed that Tet2 knockout MSCs supported the expansion of hematopoietic stem cells (HSCs) and the differentiation of HSCs was skewed towards myeloid cells. Through the dot blotting experiment, we found that the total methylation level was increased in Tet2-/- bone marrow cells (BM). We used the methylation-chip to analyze the methylation level of Tet2-/- bone marrow cells and found that the level of methylation was increased in the transcriptional starting area (TSS), exons (EXONS) and 3' untranslated region (3' UTR). Moreover, we found that the cytokines secreted by Tet2-/- MSCs, such as IL-8 and IL-18, were decreased. While the expressions of GM-CSF and CCL-3, which supported hematopoietic stem cells to differentiate to myeloid cells, were increased in Tet2-/- MSCs. Our results demonstrated that Tet2 regulates MSCs to support hematopoiesis.
Animals ; Bone Marrow Cells ; Cell Differentiation ; DNA-Binding Proteins ; Epigenesis, Genetic ; Hematopoiesis ; Hematopoietic Stem Cells ; Mesenchymal Stem Cells ; Mice ; Proto-Oncogene Proteins