Objective To explore the carrier rate of thalassemia in Laibin city,Guangxi Province,and provide a theoretical basis for the prevention and control of thalassemia.Methods From January 2020 to December 2021,88 152 patients were screened for thalassemia in the outpatient department of the Women's and Children's Hospital of 4 counties,1 city and 1 district in Laibin by blood cell detection and hemoglobin electrophoresis.The common and rare genes in initially screened positive individuals were detected by gap polymerase chain reaction(Gap-PCR)and reverse dot blot(RBD),and the results were conducted by statistical analysis.Results ① There were 22 553 positive cases in the preliminary screening and 8 327 positive cases received the diagnosis of thalassemia gene.A total of 4 944 thalassemia carriers of thalassemia genes were detected,deducing that the total thalassemia carrier rate in the population of childbearing age in this region was 15.19%,including 3 200 cases of α-thalassemia carriers(64.73%),1 424 cases of β-thalassemia carriers(28.80%),and 320 cases of were carriers α-thalassemia combined with β-thalassemia(6.47%).② There were 3 168 cases of common thalassemia(99.00%)and 32 cases of rare thalassemia(1.00%)among α-thalassemia gene carriers.A total of 13 mutant genes and 34 genotypes were detected,and genotype SEA/αα was the comes first.③ Among the β-thalassemia gene carriers,there were 1 411 cases of(99.09%)common thalassemia and 13 cases(0.91%)of rare thalassemia.A total of 19 mutant genes and 25 genotypes were detected,with CD41-42(-CTTT)being the most common.④ A total of 53 different genotypes were detected in the carriers of α-thalassemia combined with β-thalassemia,and the top genotype was--SEA/αα βCD41-42M/βN.⑤ The carrier rates of Yao and Han nationality were comparable,and the differences were not significant(χ2=0.300,P=0.584).The differences in carrying rates between Zhuang and Yao(χ2=23.66,P＜0.001),and between Zhuang and Han(χ2=116.98,P＜0.001)were significant.⑥ The carrier rate in Xiangzhou County was the highest(20.04%),while the carrier rate in Heshan City was the lowest(12.38%).⑦ The carrier rate of females was higher than that of males,and the difference was significant(χ2=182.03,P＜0.001).Conclusion The variants genotypes of thalassemia in Laibin were complex.This study was the first to investigate the carrier rate and gene mutation spectrum of thalassemia in Laibin Area,which provides valuable baseline data for genetic counseling and prenatal diagnosis.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

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.

Approximately 8%to 15%of patients with metastatic colorectal cancer(mCRC)harbor BRAF mutation,and the V600E mutation is the most common form of BRAF mutation.The prognosis of patients with metastatic colorectal cancer harboring BRAF V600E mutation is poor.Initial standard chemotherapy is often ineffective,necessitating an intensive follow-up treatment,which usually provides limited effic-acy.Consequently,the disease becomes notably difficult to treat and progresses rapidly,resulting in a decreased overall patient survival rate.This review details the research advancements in treatment of BRAF V600E-mutant metastatic colorectal cancer.

Objective To analyze the relationship between the body mass index(BMI)and anal fistula occurrence based on the results of cross-sectional survey.Methods The clinical data of 545 patients with a-nal fistula visiting in the proctology department of this hospital from March 2022 to November 2023 were ana-lyzed.The patients were divided into 4 groups based on BMI:skinny group(BMI＜18.5 kg/m2),normal group(BMI 18.5-＜24.0 kg/m2),overweight group(BMI 24.0-＜28.0 kg/m2)and obese group(BMI ≥28.0 kg/m2).The logistic regression was used to analyze the influencing factors of fistula occurrence.The dose-response relationship between BMI and the occurrence risk of anal fistula was analyzed by combining with the restricted cubic spline(RCS)model.Results The logistic regression analysis results showed that obese was the risk factor of anal fistula occurrence(OR=2.08,95％CI:1.08-3.99,P=0.028).The combining RCS a-nalysis results showed that there was a"J"shaped trend between the BMI and the risk of anal fistula.In addi-tion,smoking could increase the risk of anal fistula occurrence in obese population.Conclusion Overweight and obesity are the risk factors for anal fistula occurrence.It is suggested that the susceptible population should control their body weight reasonably to prevent the occurrence of anal fistula.

A 82-year-old man was admitted to hospital with fever,unresponsiveness,elevated hypersensitive C-reactive protein and neutrophile granulocyte.Ceftriaxone was administrated by intravenous dripping in the emergency room,but the effect was not satisfactory.Following his admission to the ward,cefoperazone sulbactam were given.Elizabethkingia meningoseptica was identified by blood culture and further confirmed by 16S rRNA sequencing.The lumbar puncture showed that cerebrospinal fluid pressure was 80 mmH2O(1 mmH2O=0.0098 kPa)and biochemical results were normal.After 11 days of cefoperazone sulbactam treatment,the patient was discharged with negative blood culture.The hypersensitive C-reactive protein and neutrophile granulocyte had also declined.The patient received levofloxacin tablets for anti-infection treatment for 14 d after discharge.No signs of infection were observed in three months'following up.

Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.

Objective: To investigate the epidemiological characteristics of overseas imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021, so as to provide insights into the prevention and control of overseas imported arthropod-borne infectious diseases. Methods: The data pertaining to imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System, and the temporal distribution, regional distribution, population distribution, sources, diagnosis and treatment of imported dengue fever and malaria cases were descriptively analyzed. Results: Totally 4 332 overseas imported dengue fever cases and 2 011 overseas imported malaria cases were reported in Yunnan Province form 2015 to 2021, which accounted for 30.09% of all reported dengue fever cases and 98.53% of all reported malaria cases. The number of overseas imported dengue fever and malaria cases peaked from August to November (83.13% of all imported dengue fever cases) and from April to July (59.08% of all imported malaria cases), and the cases were predominantly reported in Dehong Prefecture (50.99% and 58.88%), with farmers as the predominant occupation (40.21% and 67.93%). The dengue fever and malaria cases were mainly imported from Southeast Asia (99.04% and 88.21%), and the proportions of definitive diagnosis of dengue fever and malaria were 88.33% and 97.80% at township hospitals, respectively. Conclusions The number of overseas imported dengue fever and malaria cases peaked from August to November and from April to July in Yunnan Province from 2015 to 2021, and the cases were predominantly reported in Dehong Prefecture and imported from Southeast Asia, with farmers as the predominant occupation.

OBJECTIVE To study the cost-utility threshold （WTP/Q） based on the preference of the population in Liaoning province with willingness-to-pay（WTP） survey method， and to provide reference for decision-making. METHODS Using the method of questionnaire survey， quota sampling combined with snowball sampling were used to conduct telephone interviews with the general population in Liaoning province， collect data and analyze it. Probit regression combined with generalized linear model was used to analyze the relevant factors affecting WTP/Q. RESULTS A total of 755 general people were recruited. The WTP/Q of Liaoning population was 119 175 yuan，the average WTP/Q for improving the quality of life was 84 902 yuan， and the average WTP/Q for extending the survival period was 188 005 yuan. The analysis of influential factors showed that the older the age， the lower the probability of people purchasing medical interventions； the higher the education level and income， the greater the WTP/ Q； at the same time， the physical feelings of the interviewee， such as pain and depression， could also affect the WTP/Q results； compared with the scenario of improving quality of life， the WTP/Q for the extended survival period was higher. CONCLUSIONS The WTP/Q of Liaoning province based on the WTP survey method is about 2.07 times of the per capita gross domestic product of Liaoning province in the same period. The WTP/Q for extending survival period is about 2.21 times that of improving the quality of life. Therefore， interventions to improve quality of life and to extend the survival period need to be treated differently， in measurement or decision-making.