Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Nipah virus (NiV) is a highly contagious zoonotic pathogen, responsible for a relatively high mortality in human and posing a serious threat to human health. There are currently no licensed vaccines or antiviral drugs. Preclinical studies on NiV vaccines with different strategies are mainly based on NiV glycoprotein (G) and/or fusion protein (F). Internationally, three NiV vaccine candidates are currently in the Phase I clinical stage. The risk of Nipah virus transmitted to China is relatively high. In order to cope with potential future epidemics, China should develop NiV prevention and control strategies, and accelerate Nipah virus-related technology reserves and vaccine development. This article introduces NiV from the aspects of microbiology, epidemiology, clinical characteristics, and vaccine research, and puts forward prevention and control suggestions in light of the risk of NiV transmission to China and China′s national conditions, hoping to provide reference for NiV vaccine research and development.

Objective:The paper seeks to explore the characteristics of myeloid tumors with genetic DDX41 gene mutations,especially focusing on the understanding and treatment of acute myeloid leukemia with germline/somatic DDX41 mutation. Methods:One AML patient with germline/somatic DDX41 mutation who was diagnosed by using morphology,immunology,cytogenetics and molecular biology in Shanghai Shidong Hospital was retrospectively analyzed,and the patient was treated with lenalidomide combined with decitabine,and the literatures were reviewed. Results:The patient obtained complete remission after the therapy and there were no relevant adverse reactions to the treatment. Conclusion:The DDX41 gene mutations have effects on the prognosis and treatment of myeloid malignancies,and lenalidomide combined with decitabine is effective in acute myeloid leukemia with germline/somatic DDX41 mutation.The germline mutation status should be identified and confirmed early.

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

Objective:To understand the positive rate of 2019 novel coronavirus (2019-nCoV) specific IgG antibody induced by Coronavirus Disease 2019 (COVID-19) inactivated vaccine in healthy population in Xizang Autonomous Region, and evaluate the immune effect of the vaccine.Methods:Serum samples were collected from COIVD-19 vaccine immunized health population without history of 2019-nCoV infection from six prefecture-level cities in Xizang Autonomous Region. The IgG antibody against 2019-nCoV were tested by chemiluminescence method. Then, the positive rate of IgG antibody was analyzed for different immunization histories and age groups.Results:A total of 22 255 participants were enrolled in this survey. After full-access (two doses of vaccine) and booster immunization, the overall positive rate of specific IgG antibody against 2019-nCoV was 96.38%. The positive rate of IgG antibody in the booster immunized population was 97.12%, which was much higher than the 88.38% in the full-access immunization population, the difference is statistically significant ( χ2=381.11, P<0.001). There was a significant differences in the positive rates of specific IgG antibodies in different age groups ( χ2=138.28, P<0.001). Especially in the younger age groups, including less than 10 years old and the 11-20 years age group, the positive rate of specific IgG antibody were 93.44% and 89.03% respectively, which were lower than those in other age groups. Except for Naqu city and the age group ≤ 10 years old, the differences in antibody positivity rates were statistically significant between different age groups in the same region and between the different regions in the same age group for the two populations with different immunization histories ( P<0.05). Conclusions:The COVID-19 inactivated vaccine showed a good immune effect in the healthy population in Xizang Autonomous Region, and the booster immunization helps to increase the positive rate of specific IgG antibody in healthy population.

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

Objective:To explore a fast method to identify and confirm suspected clonorchis sinensis infection.Methods:For suspected clonorchis sinensis infection, the clonorchiasis serum antibody was detected first with ELISA. If the antibody was positive, the fecal examination for eggs was performed. If the fecal examination was negative, duodenal drainage under gastroscopy was recommended to detect eggs from the drainage fluid.Results:A total of 126 patients met the requirements and aged 54.14±13.33 (24- 87). There were 83 cases (65.87%, 83/126) with eggs positive in the drainage fluid, of which 53 cases were male, aged 55.91±11.47 (30-86), and 30 cases female, aged 55.87± 13.85(30-87). There was no significant difference in age between males and females( P>0.05). The time of catheterization (T1) of 126 cases was 3.79 ±1.45 min. The time of drainage (T2) of 126 cases was 31.39 ±14.29 min. There was no significant difference in T1 or T2 between the positive group and the negative group( P>0.05). The detection rates of eggs were 91.57% (76 cases) in intrahepatic bile duct drainage, 81.93% (68 cases) in the bile-cyst juice and 75.90% (63 cases) in the common bile duct fluid. No serious adverse reactions occurred during or after the operation. Conclusion:The detection rate of clonorchiosis sinensis can be effectively improved by the combination of clonorchiasis serum antibody test and gastroscopy-guided duodenal drainage.

Objective:To observe the changes of the structure and visual function of the retina in patients with or without the ectopic inner foveal layers (EIFL) and to explore the factors influencing the recovery of visual function in patients with idiopathic epimacular membrane (IMEM).Methods:A retrospective clinical study. From March 2015 to June 2019, 90 patients with MEM who were diagnosed by Ophthalmic Center of the Second Hospital of Hebei Medical University were enrolled in the study. All patients were examined by best corrected visual acuity (BCVA) and frequency domain optical coherence scan. BCVA was recorded by Snellen vision table, and it was converted into the minimum resolution angle logarithm (logMAR) vision. Among 90 eyes, IMEM grade 2-4 was 68 (75.6%, 68/90), 18 (20.0%, 18/90), 4 (4.4%, 4/90), respectively. According to this, the grade 2 was set as group A, and the grade 3 and grade 4 were combined to group B. There was no significant difference in age ( t=0.015), sex composition ratio of patients between two groups ( χ2=0.060) and the average of central macular thickness (CMT) ( F=2.277) ( P=0.904, 0.809, 0.141). The difference of average logMAR and BCVA was statistically significant ( F=35.913, P=0.000). All patients underwent 25G pars plana three channel vitrectomy with simultaneous removal of epiretinal membrane and internal limiting membrane. BCVA, CMT and improvement of IMEM grading were observed at 1, 3, 6 and 12 months after operation. BCVA, EIFL thickness and CMT were compared before and after operation by single factor repeated variance analysis; Fisher exact probability method was used to compare the changes of the anatomical structure of the eyes in the two groups at 12 months after operation. Results:1, 3, 6, 12 months after operation, the average eyes of logMAR BCVA in group A were 0.50±0.13, 0.38±0.12, 0.27±0.12, 0.19±0.10. The patients in group B were 0.66±0.14, 0.60±0.13, 0.54±0.14, 0.52±0.14. CMT in group A were 364.82±81.29, 281.65±72.45, 228.55±55.34, 182.84±56.13 μm. The patients in group B were 455.88±69.60, 440.18±68.65, 383.76±65.38, 371.39±66.60 μm. The difference was statistically significant in the two groups (BCVA: F=37.913, 11.479, 24.250, 39.013; P=0.000, 0.002, 0.000, 0.000. CMT: F=10.987, 39.610, 55.789, 79.987; P=0.002, 0.000, 0.000, 0.000). In group A, IMEM was improved to 57 eyes of grade 1 on 12 months after operation. Among the 18 eyes in group B, IMEM was improved to 1 and 3 eyes in level 1 and level 2, respectively, and no improvement was found in 4 eyes in grade 4. The difference was statistically significant ( P=0.000) in the improvement of the number of eyes in the two groups. Conclusions:The patients with IMEM without EIFL have better visual prognosis and reversible anatomical changes. EIFL is an important factor affecting the visual function and anatomical structure recovery after operation.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.