OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

Objective To evaluation the bioequivalence of telmisartan tablets(80 mg)between test formulation and reference formulation in Chinese healthy subjects.Methods A single-center,randomized,open-label,two-preparations,single administration,partial repeat crossover of three sequences in three postprandial cycles and complete repeat crossover of two sequences in four fasting cycles,bioequivalence test was designed.Chinese healthy subjects were included in the bioequivalence trial,with 33 randomly assigned to the postprandial group and 32 randomly assigned to the fasting group.In each period,blood samples was collected before and after administration.The plasma concentration of the drug was determined by LC-MS/MS,using WinNonlin version 8.3 calculate the pharmacokinetic parameters and perform a statistical analysis using SAS version 9.4.Results The main pharmacokinetic parameters of telmisartan tablets after oral administration of test or reference were as follows.Fasting group Cmax were(556.10±456.06)and(580.99±533.50)ng·mL-1;AUC0-t were(3 475.15±3 785.16)and(3 450.54±3 681.02)ng·mL-1·h;AUC0-∞ were(3 214.06±2 272.06)and(3 194.84±2 187.45)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Postprandial group Cmax were(299.26±124.72)and(291.29±126.34)ng·mL-1;AUC0-t were(3 682.24±2 799.72)and(3 636.71±2 158.42)ng·mL-1·h;AUC0-were(3 544.53±1 553.06)and(3 969.38±2 528.22)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Conclusion Under fasting and fed conditions,two kinds of telmisartan tablets are bioequivalent in Chinese healthy subjects.

Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10％L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9％NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P＜0.05,P＜0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P＜0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.

Objective To investigate the incidence and severity of symptoms in patients with gastric cancer who received chemotherapy,we constructed a symptom network to explore core symptoms and bridge symptoms.Furthermore,the study explores the association between core symptoms and Traditional Chinese Medicine(TCM)constitutions.Methods Patients with gastric cancer who received chemotherapy in the medical oncology and surgical oncology department from March to August 2023 were selected for the study using a convenience sampling method.The MD Anderson Symptom Inventory Gastrointestinal Cancer was used for evaluating gastrointestinal symptoms and their severity among patients receiving chemotherapy for gastric cancer,as well as assessing the classification of TCM constitution among patients.The symptom network model was constructed using the R programming language,and the central index was analyzed to determine the core symptoms and bridge symptoms.Binary logistic regression analysis was employed to assess the association between different physical conditions and the occurrence of core symptoms.Results A total of 346 electronic questionnaires were collected,with 340 valid ones,and the effective recovery rate was 98.3％.The 3 most prevalent and severe symptoms among the 340 patients with gastric cancer were fatigue(85.59％),lack of appetite(82.35％),and taste alteration(81.18％).The centrality index results indicated that grief exhibited the highest intensity,medium,and compactness centrality values(rs=8.23,rb=2.00,rc=0.03),making it the core symptom of this condition.Sleep disorders,lack of appetite,drowsiness,and taste alteration were identified as bridging symptoms with bridge intensities of 0.74,0.76,0.99,and 0.94 respectively.The results of Spearman correlation analysis showed that there was a positive correlation between sadness and qi-deficiency constitution,phlegm-dampness constitution(P＜0.05).The phlegm-dampness constitution was positively correlated with the taste alterations(P＜0.05).Conclusion In patients with gastric cancer,fatigue emerges as the most prominent symptom,while sadness assumes the core symptom.Additionally,sleep disorder,lack of appetite,drowsiness,and taste alteration are bridge symptoms.According to the principles of TCM constitution,qi-deficiency and phlegm-dampness are constitutions associated with a higher risk of experiencing sadness,and phlegm-dampness is a constitution associated with a higher risk of taste changes.Nurses can integrate core symptoms and TCM constitutions characteristics to optimize the strategies for symptom intervention.

ObjectiveThe objective is to investigate the possibility of isocenter dual-guided resetting of surface guided radiation therapy （SGRT） combined with image guided radiation therapy （IGRT） in postoperative radiotherapy for breast cancer. To assess the setup error accuracy between the new resetting mode and the traditional resetting mode. MethodsRetrospective analysis was performed on breast cancer patients who underwent ELEKTA infinity accelerator radiotherapy in sun yat-sen university cancer center from July 13， 2021 to October 15， 2022. According to different reset methods， the patients were divided into a simulation group （41 cases） and a dual-guided group （40 cases）. The simulation group was reset using a simulator， CBCT scans were performed and setup errors were recorded during the first treatment； The dual-guided group was guided by AlignRT and combined with CBCT for isocenter dual-guided resetting， and the setup error obtained by CBCT registration was recorded. The global setup errors of chest region of interest （CROI） ， the local residual errors of supraclavicular region of interest （SROI） and the resetting time of the two reset methods were calculated and compared respectively. The advantages of the CBCT error distribution in the dual-guided resetting of SGRT combined with IGRT were analyzed. ResultsThe median of the global setup errors （X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz°） of the simulation group and the median of the dual-guided group in the CROI were statistically significant （P<0.05） except the Rz and Ry directions. The local residual errors of the two groups of the SROI were calculated. The median of the errors of X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz° were statistically significant （P<0.05） except the X and Y axis. The resetting time of the simulation group was significantly longer than that of the dual-guided group （238.64±28.56） s， t=-24.555， P=0.000， and the difference was statistically significant （P<0.05）. The CBCT error distribution of the dual-guide group was analyzed， and it was found that the absolute values of translation errors of X， Y and Z axis were all within 0.4 cm， while the proportions of ≤ 0.3 cm were 95%， 93% and 93%， respectively. The proportions of rotation errors of Rx， Ry and Rz ≤ 1.5 ° were 90%， 93% and 90%， respectively. ConclusionIn postoperative radiotherapy of breast cancer， SGRT combined with IGRT for isocenter dual-guided resetting can effectively correct the rotational setup errors and residual errors， and improve the accuracy of radiotherapy with less resetting time and high feasibility， which compared with the traditional simulator resetting mode. This precise， unmarked resetting method can be widely used in clinical practice.

Abstract: Objective　To evaluate the completion and final effect of key parasitic disease prevention and control planning tasks in Hubei Province from 2016 to 2019, summarize the experience, find out the problems, and provide the basis for the next stage of prevention and control. Methods　According to the requirements of the Final Evaluation Plan of the National Plan for the Prevention and Control of Hydatid Disease and Other Major Parasitic Diseases (2016-2020), a retrospective survey method was adopted to collect relevant data on the implementation and safeguard measures of the prevention and control of major parasitic diseases, and population infection status in Hubei Province in 2016-2019. Results From 2016 to 2019, We carried out 2 920 992 person times of publicity and education, 209 times of prevention and control technology training, 7 680 person times of business training, with an average of 52 sessions and 1 920 person times per year. We have allocated 3.445 2 million yuan for the prevention and control of parasitic diseases, including 1.722 2 million Yuan froom provincial government, to achieved full coverage of safe drinking water in rural areas under the current national standards, and 7.687 9 million harmless toilets have been built in rural areas. From 2016 to 2019, we carried out 39 658 person times of monitoring and disease investigation, the infection rate of human liver fluke was 0, and the infection rate of soil transmitted nematode was 0.42%. While the annual infection rates varied, there was no statistically significant difference in infection rate between years (χ2＝2.276, P>0.05), but there were statistically significant differences in the infection rates between various soil nematodes (χ2=112.807, P<0.01). From 2016 to 2019, a total of 5 393 people were detected at 17 monitoring points, with the serum positive rate of 3.93% for paragonimiasis, there was a statistically significant difference in serological positive rate between years (χ2=146.011, P<0.01); a total of 738 stream crabs were collected, and the infection rate of intermediate host was 16.26%, wtih a statistically significant difference in the infection rate of stream crabs between years (χ2=49.731, P<0.01). Conclusions　From 2016 to 2019, we adhered to the prevention and control strategy of "prevention first, prevention and control combined", implemented comprehensively various prevention and control measures, and achieved remarkable results in Hubei Province. The key parasitic diseases have been in a low epidemic situation, meeting the requirements of the prevention and control objectives. But the transmission risk still exists, the next step is to continue to strengthen security and monitoring and consolidate the achievements of prevention and control.

Abstract: Objective　To collect and organize malaria case data in Hubei Province from 2017 to 2021, compare and analyze the malaria epidemic characteristics on the before and after malaria elimination, and provide scientific support for Hubei Province to further optimize the comprehensive strategies to prevent re-transmission after the elimination of malaria. Methods The study was conducted by collecting the data of reported malaria cases of Hubei during 2017-2021 from the Infectious Disease Surveillance Reporting and Management System, and conducting the epidemiological characteristics of malaria on pre-elimination (2017-2019) and post-elimination (2020-2021). Results A total of 429 cases of imported malaria were reported in Hubei Province from 2017 to 2021, and the malaria epidemic showed an obvious trend of rising first and then falling. On the pre-malaria elimination, 374 malaria cases were reported, including 262 cases of P.falciparum (70.05%); on the post-malaria elimination, 55 malaria cases were reported, including 25 cases of P.falciparum (45.45%). There was a statistically significant difference in the proportion of infections caused by the four types of malaria parasites before and after the elimination of malaria (χ2=14.248, P<0.05). On the pre-malaria elimination, the peak of disease onset mainly occurred in January, July, and November; on the post-malaria elimination, the peak of disease onset mainly occurred in January to February, and December. Both before and after malaria elimination, the reported cases were mainly concentrated in Wuhan, Yichang, Huangshi, Xiangyang, Shiyan and Huanggang, but the range of cases showed a clear trend of narrowing. Before and after malaria elimination, malaria cases in Hubei Province were mainly among young and middle-aged males aged 30-49. The proportions of workers and migrant workers increased from 37.70% and 9.09% before the elimination to 50.91% and 18.18% after the elimination, respectively, with a statistically significant difference (χ2=17.839, P<0.05). The percentage of interval from onset of illness to initial diagnosis ≥ 5d decreased from 21.66% before the elimination to 10.91% after the elimination (χ2=6.448, P<0.05). The percentage of definitive diagnosis of malaria at initial diagnosis in town clinic increased from 18.18% before the elimination to 50.00% after the elimination. The proportion of malaria cases diagnosed by county-level medical institutions increased from 22.73% before the elimination to 34.55% after elimination. There was no statistically significant difference in the proportion of malaria cases diagnosed by medical institutions at all levels before and after the elimination of malaria (χ2=5.630, P>0.05). The proportion of cases with the interval between initial diagnosis and diagnosis within 24h increased from 43.85% before the elimination to 70.91% after the elimination. There was a statistically significant difference in the proportion of cases with the interval between initial diagnosis and diagnosis before and after the elimination of malaria (χ2=14.006, P<0.05). Before and after malaria elimination, all reported cases were mainly imported from African countries. Conclusions There are imported malaria cases reported every year in Hubei Province before and after the elimination of malaria, which poses a great challenge to the prevention of re-transmission. Therefore, it is necessary to strengthen the surveillance system, detect and standardize the treatment of imported malaria cases in a timely manner, conduct targeted retransmission risk surveys and assessments, and consolidate the achievements of malaria elimination.