BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P＜0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P＜0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

OBJECTIVE: To explore and design a novel bi-specific chimeric antigen receptor (CAR) structure. To obtain the corresponding CAR-T cells and verify killing effects on tumor cells in vitro and in vivo. METHODS: Five kinds of bi-specific CAR structures including humanized CD19 scFv and CD79b scFv, CD8 hinge & TM-4-1BB-CD3ζ and/or CD3ε chain intracellular regions were constructed and prepared. CAR-19-79b cells were obtained. Five kinds of CAR-T cells were co-incubated with the 3M-CD19-CD79b-Luc target cells. Luciferase assay and ELISA were used to detecte the killing ability of these five groups of CAR-T cells and the secretion of cytokines and compared. The optimal structure of CAR-T cells was used to treat the leukemia mouse model constructed by Daudi-Luc cells. And the treatment efficacy was evaluated. At the same time, other targets were used in this structure. With the same methods, the stability and effectiveness of the structure were verified. RESULTS: CAR-19-79b-T cells were cultured for 7 days, the expression rates of CAR-19 and CAR-79b were 21.6%-36.3% and 21.7%-37.8%, respectively. The killing rates of 5 kinds of CAR-19-79b-T cells prepared by T cells from 3 healthy donors on 3M-CD19-CD79b-Luc cells were significantly higher than those of the T cell control group at the effect-target ratio of 10∶1. Among them, the killing rates of CAR-19-79b-T cells with No. III and No. IV structures were the strongest. After co-incubation with 3M-CD19-CD79b-Luc target cells, the amount of IFN-γ and TNF-α secreted by CAR-T cells with CAR IV and CARV structures was the lowest. And there was no significance between the two groups (P>0.05). CAR IV cells with remarkable killing effect and low secretion factor had obvious therapeutic effect on Daudi-Luc leukemia mice, extending the survival period of mice to 64 days. And all mice in the T cell control group died at 41.0±2.4 days. The CAR-19-BCMA-T and CAR-19-22-T with the same structure showed significant killing ability and low cytokine expression levels. CONCLUSION A novel bi-specific CAR structures was successfully designed, which could efficiently kill the corresponding tumor cells and secrete less cytokines (such as TNF-α, IFN-γ). Moreover, it shows obvious therapeutic effect on Daudi lymphoma mouse model. The bi-specific CAR structure shows good killing specificity and safety.
Animals ; Mice ; Leukemia ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

Animals ; Electrophoresis, Gel, Two-Dimensional ; Male ; Muscles ; Physical Conditioning, Animal ; Proteome ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To observe the regulatory effect of electroacupuncture (EA) on small airway function and exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A total of 62 patients with stable COPD were randomized into an observation group (31 cases, 1 case dropped off) and a control group (31 cases, 5 cases dropped off). On the base of routine medication and aerobic exercise, the patients of the two groups all received EA at Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and Yingchuang (ST 16). In the observation group, filiform needles were used and inserted perpendicularly, 3 mm in depth. In the control group, the placebo needling method was performed, in which the needle was not inserted through skin at each point. In both groups, electric stimulation with low-frequency electronic pulse instrument was exerted, with continuous wave, 2 Hz in frequency, lasting 30 min each time in the two groups. The treatment was given once every other day, 3 times a week, for 14 treatments totally. Before and after treatment, the following indexes were compared in patients between the two groups, i.e. the lung function indexes (forced expiratory volume in first second [FEV1], forced vital capacity [FVC], the ratio of FEV1 to FVC [FEV1/FVC], maximal voluntary ventilation [MVV], the percentage of maximal expiratory flow [MEF] at 25% of FVC exhaled [MEF25], MEF50 and MEF75 in predicted value), cardiopulmonary exercise test indexs (metabolic equivalent [METS], oxygen uptake per kg body weight [VO RESULTS: After treatment, FVC%, MVV%, MEF75%, MEF50%, VO CONCLUSION Electroacupuncture can improve the respiratory function and exercise tolerance in COPD patients through removing small airway obstruction and increasing ventilation.
Electroacupuncture ; Exercise Tolerance ; Forced Expiratory Volume ; Humans ; Pulmonary Disease, Chronic Obstructive/therapy* ; Respiratory Function Tests

Objective To understand pathogenic distribution and epidemiological characteristics of diarrhea syndrome in Gansu Province． Methods Fecal specimens from diarrhea syndrome surveillance cases at sentinel hospitals in Gansu Province from 2009 to 2018 were collected，and virus nucleic acids were detected by real－time fluorescent chain reaction，and bacteria were detected by isolation culture． Ｒesults 1 547 positive cases were detected from 4 406 stool specimens with the positive rate of 35. 11%． Among the positive samples，1 281 cases were positive for virus with the positive rate of 47. 20%; 287 ca- ses were positive for bacteria with the positive rate of 8. 57%． Top five of pathogenic spectrum were rota- virus ( 46. 04%) ，astrovirus ( 13. 37%) ，norovirus ( 13. 15%) ，Shigella ( 9. 90%) and adenovirus ( 7. 81%) ． In different age groups，statistically significant differences were found in the positive rates of rotavirus，norovirus，astrovirus，Shigella and non typhoid Salmonella ( all P＜0. 05) ． The positive rate of virus was higher from November to March of next year，and the positive rate of bacteria was higher from June to August． The epidemic seasons of pathogens were different，of which rotavirus was dominating in four seasons． Conclusions The pathogenic spectrum of diarrhea is wide relatively in Gansu Province， and viral diarrhea is more common，with obvious seasonal peak． Continuous monitoring should be strengthened to grasp characteristics and epidemic trends of pathogens，and it is helpful to take targeted and seasonal preventive measures in population at high risk．