OBJECTIVE To evaluate the cost-effectiveness of fluzoparib monotherapy versus combination with apatinib as second-line or later-line treatment for patients with germline BRCA1 / 2 -mutated human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， from the perspective of the Chinese healthcare system. METHODS Based on the FABULOUS trial， a partitioned survival model was developed to simulate disease progression， with a cycle length of 21 days and a time horizon of 10 years. A discount rate of 4.5% per annum was applied. Model outputs included total costs and quality-adjusted life years （QALYs）. Cost-utility analysis was conducted by comparing the incremental cost-effectiveness ratio （ICER） between the two regimens against a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product in 2025 （199 330 yuan/QALY）. Robustness of the base-case results was tested through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analyses. RESULTS For patients with germline BRCA1/2 -mutated HER2－ metastatic breast cancer， fluzoparib combination with apatinib provided greater health benefits （1.91 QALYs vs. 1.69 QALYs） and incurred lower total costs （1 634 119.3 yuan vs. 1 855 264.2 yuan） compared with fluzoparib monotherapy， thus representing a dominant strategy. One-way sensitivity and probabilistic sensitivity analyses confirmed the robustness of the base-case findings. Scenario analyses showed that the conclusion remained robust when the time horizon was shortened to 5 years or when the discount rate was changed to 3%； however， the results reversed when the extrapolation distribution model was altered. CONCLUSIONS Under the current WTP threshold， compared with fluzoparib monotherapy， the combination of fluzoparib and apatinib is more cost-effective as a second-line or later-line treatment for Chinese patients with germline BRCA1 / 2 -mutated HER2－ metastatic breast cancer.

ObjectiveTo evaluate the corrective effects of a three-stage structured Tai Chi training program on abnormal neck and shoulder posture from a biomechanical perspective. MethodsEighty-two participants with abnormal neck and shoulder posture were randomly assigned to a treatment group and a control group， with 41 participants in each group. The treatment group received three-stage structured Tai Chi training six times per week， while the control group received online health education once per week. Both interventions lasted for 12 weeks. The primary outcome cervical postural deviation angle， and the secondary outcomes including cervical loading and bilateral shoulder horizontal deviation angle， were assessed before intervention， after 6 weeks and 12 weeks of intervention. Safety was also evaluated. ResultsUltimately， 40 participants from each group were included in the analysis. In the treatment group， cervical postural deviation angle and cervical spine loading were significantly reduced after 12 weeks of intervention compared with baseline and after 6 weeks of intervention. The bilateral shoulder horizontal deviation angle decreased significantly after both 6 and 12 weeks of intervention compared with baseline （P＜0.05）. In the control group， cervical spine loading was reduced after 6 and 12 weeks of intervention compared with baseline （P＜ 0.05）. After 12 weeks of intervention， the treatment group showed lower cervical postural deviation angle and bilateral shoulder horizontal deviation angle than the control group， whereas cervical loading was higher in the treatment group after 6 weeks of intervention （P＜0.05）. Significant differences were observed between groups in the changes from baseline to week 12 for cervical postural deviation angle and bilateral shoulder horizontal deviation angle， as well as in the changes from baseline to week 6 for cervical loading and bilateral shoulder horizontal deviation angle （P＜ 0.05）. No significant adverse events occurred in either group during the intervention period. ConclusionThree-stage structured Tai Chi can effectively improve abnormal neck and shoulder posture， demonstrating good safety and feasibility.

ObjectiveTo systematically evaluate the measurement content, psychometric properties and quality of evidence of patient-reported outcome measures (PROMs) for adolescents with spinal dysfunction based on International Classification of Functioning, Disability and Health-Children and Youth (ICF-CY) framework, Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) and modified GRADE approach. MethodsDatabases including CNKI, Wanfang Data, PubMed, Embase and Web of Science were systematically searched for studies assessing psychometric properties of PROMs targeting adolescents with spinal dysfunction. The methodological quality of included studies was evaluated using COSMIN Risk of Bias checklist, the psychometric properties were rated according to COSMIN criteria, and evidence quality was graded using modified GRADE approach. Item content of each PROM was coded following the ICF-CY linking rules. ResultsA total of 23 studies involving eight PROMs were included. Brace Questionnaire (BrQ), Italian Spine Youth Quality of Life Questionnaire (ISYQOL), Quality of Life Profile for Spinal Deformities (QLPSD), Spinal Appearance Questionnaire (SAQ), Scoliosis Japanese Questionnaire-27 (SJ-27) and Scoliosis Research Society-22 Revised Questionnaire (SRS-22r) were rated as grade B, while EuroQol Five-Dimension Youth Five-Level Questionnaire (EQ-5D-Y-5L) and Young Spine Questionnaire (YSQ) were rated as grade C. The eight PROMs were linked to six to 24 ICF-CY categories. BrQ covered the largest number of categories (n = 24), followed by SJ-27 (n = 19) and SRS-22r (n = 16). Except for SAQ which mainly focused on dimension of body functions and structures, all other PROMs covered both dimension of body functions and structures, and activities and participation, while BrQ, ISYQOL, SRS-22r and YSQ also covered dimension of environmental factors. Major methodological limitations included insufficient evidence for content validity, inappropriate factor-analysis approaches, incomplete reporting for test-retest reliability, and overall scarcity of evidence concerning measurement error, minimal important change (MIC) and responsiveness. ConclusionThe quality of PROMs in adolescents with spinal dysfunction varies. BrQ, ISYQOL, QLPSD, SAQ, SJ-27 and SRS-22r show application potential, yet further high-quality studies are required to supplement their psychometric evidence. EQ-5D-Y-5L and YSQ exist high-quality insufficient evidence. Selection of PROMs should comprehensively consider target population, measurement purpose, content coverage and quality of evidence. Further researches are needed to improve reporting quality.

Objective: To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis. Methods: Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting. Results: There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05). Conclusion The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.

Objective To evaluate the effects of physical exercise on liver function and size in adolescents.Methods A total of 361 adolescent subjects from Jining,Shandong Province were selected and divided into low,moderate,and high-intensity exercise groups according to the frequency of moderate intensity exercise.Physical ex-amination tests were conducted including morphological indicators,blood biochemical indicator measurements,liver size and the presence of non-alcoholic fatty liver disease.Independent sample t-tests and variance analysis were per-formed using SPSS 26.0,and correlation analysis was conducted using Spearman correlation analysis and multivari-ate linear regression analysis.Results Compared with the moderate and low-intensity exercise groups,the high-intensity exercise group had significantly lower diastolic blood pressure,homeostatic model assessment of insulin resistance(HOMA-IR),and triglycerides(TG),as well as significantly higher height,maximum oblique diameter of the right liver lobe,and direct bilirubin(DBIL).Correlation analysis showed that as exercise intensity in-creased,aspartate aminotransferase/alanine aminotransferase,DBIL,and the maximum oblique diameter of the right liver lobe increased significantly(P＜0.05).The results of the cumulative effect of exercise type and intensity indicate that exercise type does not influence the effect of exercise intensity on liver function and size.Conclusions Regular exercise in adolescents can not only shape body,but also improve glucose and lipid metabolism and en-hance liver function.

OBJECTIVE: To observe the efficacy and safety of Tiaowei Jiannao acupuncture (acupuncture for regulating defensive qi and nourishing brain) for post-ischemic stroke insomnia (PISI). METHODS: A total of 96 patients with PISI were randomized into an acupuncture group (32 cases, 1 case was excluded), a medication group (32 cases, 1 case dropped out, 1 case was excluded) and a sham-acupuncture group (32 cases, 1 case dropped out, 1 case was excluded). In the acupuncture group, Tiaowei Jiannao acupuncture was applied at bilateral Shenmai (BL62), Zhaohai (KI6), Hegu (LI4), Taichong (LR3), and Baihui (GV20), Sishencong (EX-HN1), Yintang (GV24⁺), Shenting (GV24), once a day, 1-day interval was taken after 6-day treatment, for 3 weeks totally. In the medication group, eszopiclone tablet was given orally, 1-3 mg a time, once a day for 3 weeks. In the sham-acupuncture group, non-invasive sham acupuncture was applied, the acupoint selection, frequency and course of treatment were the same as the acupuncture group. Before treatment, after 2,3 weeks of treatment, the scores of Pittsburgh sleep quality index (PSQI), self-rating sleep scale (SRSS), National Institutes of Health Stroke scale (NIHSS), Hamilton depression scale-17 (HAMD-17) were observed; before and after treatment, the sleep parameters were recorded using polysomnography (PSG); and the efficacy and safety were evaluated after treatment in the 3 groups. RESULTS: After 2,3 weeks of treatment, the scores of PSQI, HAMD-17 and SRSS in the acupuncture group and the medication group, as well as the SRSS scores in the sham-acupuncture group were decreased compared with those before treatment (P<0.05); after 2 weeks of treatment, the NIHSS score in the acupuncture group was decreased compared with that before treatment (P<0.05); after 3 weeks of treatment, the NIHSS scores in the acupuncture group, the medication group and the sham-acupuncture group were decreased compared with those before treatment (P<0.05). After 3 weeks of treatment, the scores of PSQI, SRSS, HAMD-17 and NIHSS in the acupuncture group and the medication group, as well as the NIHSS score in the sham-acupuncture group were decreased compared with those after 2 weeks of treatment (P<0.05). After 2,3 weeks of treatment, the scores of PSQI, SRSS and HAMD-17 in the acupuncture group and the medication group were lower than those in the sham-acupuncture group (P<0.05), the NIHSS scores in the acupuncture group were lower than those in the medication group and the sham-acupuncture group (P<0.05); after 3 weeks of treatment, HAMD-17 score in the acupuncture group was lower than that in the medication group (P<0.05), the NIHSS score in the medication group was lower than that in the sham-acupuncture group (P<0.05). Compared before treatment, after treatment, the total sleep time was prolonged (P<0.05), the wake after sleep onset, sleep latency, and non-rapid eye movement (NREM) sleep latency were shortened (P<0.05), the sleep efficiency was improved (P<0.05), the number of awakenings was reduced (P<0.05), the percentage of rapid eye movement (REM%) and the percentage of NREM stage 1 (N1%) were decreased (P<0.05), the percentage of NREM stage 2 (N2%) and the percentage of NREM stage 3 (N3%) were increased (P<0.05) in the acupuncture group and the medication group; the sleep latency was shortened in the sham-acupuncture group (P<0.05). After treatment, the PSG indexes in the acupuncture group and the medication group were superior to those in the sham-acupuncture group (P<0.05); in the acupuncture group, the number of awakenings was less than that in the medication group (P<0.05), the REM% and N1% were lower than those in the medication group (P<0.05), the N2% and N3% were higher than those in the medication group (P<0.05). The total effective rate were 93.5% (29/31) and 90.0% (27/30) in the acupuncture group and the medication group respectively, which were higher than 10.0% (3/30) in the sham-acupuncture group (P<0.05). There was no serious adverse events in any of the 3 groups. CONCLUSION Tiaowei Jiannao acupuncture improves the insomnia symptoms in patients with ischemic stroke, improves the quality of sleep, increases the deep sleep, promotes the recovery of neurological function, and relieves the depression. It is effective and safe for the treatment of PISI.
Humans ; Acupuncture Therapy ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Ischemic Stroke/complications* ; Stroke/complications* ; Sleep

A wealth of prior studies has confirmed that intratumoral microbiota can survive within tumor tissue, thereby promoting or inhibiting tumor growth. With the development of high-throughput sequencing and metabolomics, increasing attention has been paid to the correlation between intratumoral microbiota and host metabolism, and their effect on tumorigenesis and progression. This review focuses on the interaction between intratumoral microbiota and tumor metabolism. It emphasizes the effects of intratumoral microbiota on tumor sugar, lipid, and amino acid metabolism and explores emerging therapeutic strategies for guiding tumor prevention and treatment by modulating tumor metabolism. Although the specific role of intratumoral microbiota in tumor metabolism remains to be further studied, a deepened understanding of the interaction between tumor-specific microbiota and tumor metabolism may provide new directions and application prospects for tumor prevention and treatment.

Objective:To establish a method of dual nueleic acid test strips for rapid detection of Bacillus cereus cytK and nhe toxin genes based on polymerase chain reaction(PCR)and colloidal gold technique,and to evaluate its specificity,sensitivity,repeatability and stability.Methods:Bacillus cereus DNA was extracted by boiling method.Specific primers were designed with Bacillus cereus cytK and nhe as the target genes.Clonal transformation was used to identify the PCR products.The optimal labeling amounts of colloidal gold-labeled streptavidin,quality control line(C line),cytK detection line(T1)and nhe detection line(T2)were determined.The nucleic acid test strips were assembled and its specificity,sensitivity,reproducibility and stability were evaluated.Results:The DNA concentration of Bacillus cereus was 248 mg·L-1,and the purities were 1.8-2.0.After cloning and plasmid sequencing,the similarities between the PCR products and the sequences of cytK and nhe registered in the GenBank database were 100％.Under the condition of pH 7.0,the optimal amount of streptavidin labeling per 200 μL of colloidal gold solution was 6.0 μL;the optimal marking amount was 2.00 g·L-1 for the quality control line(C line),0.550 g·L-1 for cytK gene detection line(T1)and 0.2 g·L-1 for nhe gene detection line(T2).In the specificity test,positive result on the test strips was seen only for Bacillus cereus,and no cross-reactivity was observed for Staphylococcus aureus,Escherichia coli,Pseudomonas aeruginosa and Bacillus subtilis,which were consistent with the electrophoresis results.Sensitivity assay showed that even when DNA concentration was reduced to 10-2 mg·L-1,three bands(C line,T1 line and T2 line)could be observed,and the detection limit of the test strip was one-tenth of agarose gel electrophoresis(10-1 mg·L-1).The nucleic acid test strips were verified by different operators in different laboratories,and the results were consistent.The stability of the test strips was verified at the 6th,9th and 12th months,and the results showed good stability.Conclusion:The dual nucleic acid test strip method established in this study can simutaneously detect the cytK and nhe toxin genes of Bacillus cereus with high sensitivity and specificity,achieving short-term visual detection.

Objective:To establish a rapid detection method for pathogenic microorganisms by combining loop-mediated isothermal amplification(LAMP)and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 12a(Cas12a)(CRISPR-Cas12a)system,and to evaluate its efficacy for detecting the thermolabile hemolysin(tlh)gene of Vibrio parahaemolyticus(Vp).Methods:Using the tlh gene of Vp as the target gene,LAMP primers and CRISPR RNA(crRNA)were designed to construct and optimize the optimal concentration ratio of each component in the LAMP-CRISPR detection system.Bacillus cereus,Staphylococcus aureus,and Escherichia coli were used as control groups,and the specificity,sensitivity,reproducibility and positive conformity rate were verified to establish a rapid LAMP-CRISPR/Cas12a method for detecting the tlh gene of Vp.Results:The method specifically detected Vp,while Bacillus cereus,Staphylococcus aureus,and Escherichia coli yielded negative results.The DNA extraction concentration of Vp was 190.67 mg·L-1 with an A(260)/(A280)ratio of 1.84.Under the reaction conditions of 37℃ with 80 cycles for 40 min using quantitative PCR(qPCR)method,when the concentrations of Cas12a protein and crRNA in the LAMP-CRISPR/Cas12a system were 50 nmol·L-1,the visual brightness and relative fluorescence intensity peaks were high.The sensitivity of LAMP CRISPR/Cas12a for detecting Vp DNA concentration could reach 10-6 mg·L-1.The reproducibility test results showed that different experimenters had consistent results in different experimental environments and times.Conclusion:The established LAMP-CRISPR/Cas12a method can rapidly detect the tlh gene of Vp with high sensitivity and specificity,and can achieve short-term visual detection in the field.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.