Based on the theory that Shaoyang （少阳） and Shaoyin （少阴） function as the principal pivots， and integrating the laws of qi-fire transformation， yin-yang alternation， and the waxing and waning of healthy qi and pathogenic factors， as well as the action characteristics of immune checkpoint inhibitors （ICIs）， this study systematically expounds the dynamic evolution laws of the Shaoyang and Shaoyin pivots and constructs a stage- and phase-based differentiation and treatment framework for gastric cancer immunotherapy. In the neoadjuvant treatment stage， the core pathogenesis is the dysfunction of the Shaoyang pivot and the disorder of qi and fire transformation， often accompanied by stagnation of cold-deficiency in the middle jiao （焦）. In the postoperative adjuvant treatment stage， the dominant factors are the depletion of Shaoyin fire and the damage of yin fluid， accompanied by the lingering of residual pathogen in the Shaoyang level and the obstruction of collaterals by phlegm and stasis. In the advanced stage， the critical conditions are the exhaustion of the Shaoyin pivot， the blockage of orifices by turbid toxins， and the separation of yin and yang， leading to the rampant of pathogenic toxins and the emergence of various complicated syndromes. The treatment should be guided by the principle of regulating the double pivot. In the neoadjuvant treatment stage， it is recommended to activate the Shaoyang pivot and warm and promote the qi movement in the middle jiao. In the postoperative adjuvant treatment stage， clearing the residual pathogenic factors from the pivot and nourishing the Shaoyin. In the advanced stage， rescuing the Shaoyin pivot and opening the orifices to transform turbidity. Furthermore， stage-based treatment should serve as the foundation for dynamically assessing the patient's immune status and phase-specific changes in immunity， thereby promoting immune activation while preventing and managing immune overactivation and drug resistance.

OBJECTIVE To develop a pharmacist-led intervention model for reducing drug-related medical insurance claim denial risks， so as to provide practical references for healthcare institutions in fulfilling their primary responsibility for medical insurance fund supervision. METHODS A risk matrix method was employed by the pharmacists to assess the risks associated with drug‑related medical insurance claim rejections in our hospital during 2024. Intervention measures were developed targeting high‑risk factors (including inappropriate indications for medical insurance coverage, exceeding the covered treatment course, and inappropriateness of gender and age) from three dimensions, namely organizational structure, technical prevention and control, and closed‑loop management. Changes in drug‑related claim rejection data were compared between 2024 (pre‑intervention) and 2025 (post‑intervention), and the interception effect of the pre‑prescription review system was evaluated after the intervention. RESULTS After the intervention, the total amount of drug‑related medical insurance claim rejections in our hospital was reduced by 57.24% compared with that before the intervention, and the number of rejected items decreased from 10 108 to 2 892. Specifically, the number of rejected items due to inappropriate indications, exceeded treatment course, inappropriate gender, and inappropriate age was reduced by 70.94%, 74.26%, 83.86%, and 96.70%, respectively. Throughout the year following the intervention, a total of 5.605 yuan million in outpatient prescription drug amounts and 4.683 million yuan in inpatient medication order amounts that did not meet the insurance‑limited payment requirements were intercepted by the pre‑prescription review system. The proportion of drug‑related claim rejection amount to the total medical service claim rejection amount of our hospital decreased to 19.7%. CONCLUSIONS The pharmacist-led multi-department collaborative， technical prevention and control， and dynamic optimization integrated full-process intervention model is highly operable and has significant practical effects. It has important promotion value in reducing drug-related medical insurance claim denial risks.

Objective To evaluate the efficacy and safety of a combination therapy regimen comprising stereotactic body radiation therapy (SBRT) combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy (CAP) in patients with advanced bone and soft tissue sarcomas. Methods This study is a prospective subgroup analysis of the multicenter, open-label, single-arm phase Ⅱ CAP trial (NCT04569916), which enrolled 60 patients with advanced solid tumors who had progressed after standard therapy between November 2020 and February 2023, including 11 patients with advanced bone and soft tissue sarcomas. All patients received sequential liposomal irinotecan within 48 hours after stereotactic body radiotherapy (SBRT), followed by maintenance therapy with camrelizumab and an anti-angiogenic agent until disease progression or intolerable toxicity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results In the bone and soft tissue sarcoma subgroup (n=11), three patients achieved partial response (PR), five had stable disease (SD), and three experienced disease progression (PD). ORR was 27.3%, and DCR was 72.7%. mPFS was 5.8 months (95%CI: 2.2-10.3), and mOS not reached. Regarding safety, adverse reactions primarily included bone marrow suppression, fatigue, and gastrointestinal reactions, indicating overall manageable toxicity. Conclusion As a subgroup analysis of the CAP study, this research suggests that radiotherapy combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy demonstrates certain efficacy in advanced bone and soft tissue sarcomas that have failed multiple lines of treatment, with overall manageable adverse reactions. Future studies should expand the sample size.

ObjectiveTo investigate the metabolic mechanisms of Limosilactobacillus reuteri （L. reuteri） in alleviating chemotherapy-induced intestinal mucosal injury （CIMI）. MethodsC57BL/6 mice were randomly divided into the Control group， Model group， and L. reuteri treatment group （n=8 per group）. Mice in the L. reuteri group were intragastrically administered L. reuteri （1 × 10⁹ CFU/mL） for 10 consecutive days. From day 5， mice in the Model and L. reuteri groups were intraperitoneally injected with 5-FU （65 mg/kg） for 6 consecutive days to establish a CIMI model. Body weight changes， colon length， and related indicators were recorded. Intestinal histopathological injury was assessed by HE staining with measurement of villus height and crypt depth. The expression levels of zonula occludens-1 （ZO-1）， Occludin， Claudin-4， Muc1， and Muc2 in ileal tissues were determined by RT-qPCR and immunohistochemistry to evaluate intestinal barrier function. In addition， untargeted metabolomics was performed on cecal contents from each group to analyze metabolic profiles and enrichment of differential metabolic pathways. ResultsL. reuteri intervention significantly alleviated body weight loss （P<0.001） and colon shortening （P<0.05） in CIMI mice， effectively reducing ileal tissue pathological damage， and upregulating the expression of ZO-1， Occludin， Claudin4， Muc1， and Muc2 （P<0.05）. Untargeted metabolomics analysis showed that L. reuteri treatment reversed the abnormal metabolic profile in the cecal contents of CIMI mice， bringing it closer to normal. Various differential metabolites， such as acylcarnitines and polyunsaturated fatty acids， might play an important role in L. reuteri-mediated alleviation of CIMI. These differential metabolites were primarily enriched in key pathways such as linoleic acid metabolism， tryptophan metabolism， and unsaturated fatty acid biosynthesis. ConclusionThis study reveals that L. reuteri improves intestinal barrier function and alleviates CIMI by regulating the intestinal metabolic profile， particularly lipid and amino acid metabolism. It provides a novel potential strategy for the prevention and treatment of CIMI.

AIM: To construct an assessment model for the risk of myopia in preschool children and evaluate its clinical value.METHODS: A retrospective analysis was conducted on the data of preschool children who established refractive profiles in our hospital from January 2020 to December 2024. The eye with lower refractive error was selected. The right eye was chosen in cases where the refractive error of both eyes was identical. The data were divided into a training set(n=385)and a validation set(n=165)in a 7∶3 ratio. The data of the children were collected in detail, and the children's spherical equivalent(SE)was used as the dependent variable. The multiple linear regression model was used to screen the indicators that affected the biological indicators related to myopia in preschool children.Subsequently, the children in the training set were divided into a myopia group and a normal vision group based on whether myopia occurred(SE≤-0.50 D can be diagnosed as myopia according to refractive power assessment). Subsequently, the influencing factors selected by the multiple linear regression model were included as predictive variables, and a risk assessment equation was constructed using Logistic regression. The discrimination, calibration and clinical application value of the assessment model were verified through the receiver operating characteristic(ROC)curve, Hosmer-Lemeshow test and decision curve.RESULTS: This study included 550 preschool children(550 eyes). The training set comprised 385 children(385 eyes; 190 boys and 195 girls), and the validation set comprised 165 children(165 eyes; 82 boys and 83 girls). Among the children in the training set, the myopia group included 34 children(34 eyes; 16 boys and 18 girls), and the non-myopic group included 351 children(351 eyes; 174 boys and 177 girls). Multiple linear regression analysis showed that the ratio of axial length(AL)to corneal curvature radius(CR), subfoveal choroidal thickness(SFCT), anterior chamber depth(ACD), age, parental myopia history, and outdoor activity time were risk factors for myopia in preschool children(all P<0.05). Based on the above risk factors, a Logistic regression risk assessment model was constructed, and the evaluation model Logit(P)was obtained as 0.894×AL/CR-1.312×SFCT+1.182×ACD+2.063×age+0.763×parental myopia history-5.868. The effectiveness of the myopia risk assessment model for preschool children based on the training set was evaluated. The results showed that the area under the ROC curve(AUC)was 0.939(95%CI: 0.912-0.965), the H-L test was χ2=1.487, P=0.993, and the decision curve indicated that within the threshold range of 0.03-0.81 and 0.89-0.97, the net return rate was greater than 0. This suggested that the model had good discrimination, calibration, and clinical application value in evaluating the myopia risk and actual risk of preschool children. Internal validation was conducted in an independent validation set, and the results showed that the AUC of the ROC curve was 0.967(95%CI: 0.919-1.000), the H-L test was χ2=3.818, P=0.873, and the decision curve indicated that within the threshold range of 0.01-0.99, the net return rate was greater than 0, further suggesting that the model assessment had good consistency with the actual risk.CONCLUSION: Age, parental history of myopia, AL/CR, SFCT, and ACD are risk factors for myopia in preschool children. The Logistic regression risk assessment model constructed based on these factors has high evaluation value and can effectively evaluate the probability of myopia occurrence in individuals, providing reference for individualized prevention of myopia risk in preschool children.

Grounded in the theory that "diffusing therapy can eliminate congestion"， this paper proposes that "congestion" runs through the entire course of breast cancer-related lymphedema （BCRL）. In treatment， the causes of congestion should be clearly differentiated， with diffusing and unblocking to promote flow and transformation as the therapeutic principle， so as to eliminate the congested state at different stages. In the early stage， stagnation of qi and dampness obstructs the vessels and collaterals， for which treatment is aimed at diffusing qi， promoting urination to drain dampness， soothing the liver and unblocking the collaterals， with modified Chaihu Shugan Powder （柴胡疏肝散） combined with Shengxian Decoction （升陷汤）. In the progressive stage， exuberant phlegm and stasis cause water to flood the three jiao （焦）， and the treatment is aimed at dispersing and freeing three jiao， resolving stasis and promoting diuresis， with modified Wuling Powder （五苓散） combined with Danggui Shaoyao Powder （当归芍药散）. In the advanced stage， turbid toxin congeals and obstructs， with blood and water bound together； treatment is aimed at diffusing and outthrusting turbid toxin， breaking stasis and expelling water， with modified Simiao Yongan Decoction （四妙勇安汤） combined with Shengjiang Powder （升降散）. Throughout the disease course， the principles of diffusing and unblocking to promote flow and transformation should be followed， with dynamic differentiation and treatment according to the three stages， in order to provide a theoretical reference for the clinical management of BCRL.

[Purpose]To analyze the incidence and changing trends of elderly breast cancer(de-fined as diagnosis at age ≥ 60 years old)in China and globally from 1990 to 2021,and to predict its trends from 2022 to 2035.[Methods]Data on the number of new cases and crude incidence rate of elderly breast cancer in China and globally were extracted from the 2021 Global Burden of Disease Study(GBD)database.The age-standardized incidence rate(ASIR)was calculated by sex and age group.The Joinpoint regression model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC),to describe the incidence trend of elderly breast cancer from 1990 to 2021.The Bayesian age-period-cohort(BAPC)model was applied to predict the incidence of elderly breast cancer from 2022 to 2035.[Results]From 1990 to 2021,the number of new breast cancer cases among elderly individuals globally increased from 416 444 to 1 023 776,while in China,the number rose from 26 371 to 158 085.The ASIR increased from 89.04/105 to 94.73/105 globally and from 27.24/105 to 58.40/105 in China.By sex,the ASIR of el-derly females increased from 155.19/105 to 170.54/105 globally and from 49.13/105 to 106.00/105 in China;the ASIR of elderly males increased from 2.78/105 to 4.72/105 globally and from 1.69/105 to 6.81/105 in China.By age group,from 1990 to 2021,the incidence rates of breast cancer in elderly female and male both peaked in the age group of 85～89 years old globally.In China,the most significant increases in incidence rates were observed in the age group of 60～64 years old for elderly females and the age group of 70～74 years old for elderly males;these two age groups had the highest incidence rates in their respective sexes in 2021.Joinpoint analysis showed that the ASIR of elderly breast cancer in China presented a continuous upward trend from 1990 to 2021(AAPC=2.51％),with the fastest growth during 2016-2019(APC=5.14％).The global ASIR showed only a slight fluctuating upward trend(AAPC=0.20％),with significant increases only during 1990-1995 and 2003-2010.Predictions from the BAPC model indicated that by 2035,the global ASIR of elderly breast cancer would reach 107.84/105(192.26/105 for females and 6.02/105 for males),while the ASIR in China would reach 104.35/105(188.08/105 for females and 13.32/105 for males).[Conclusion]From 1990 to 2021,the incidence of elderly breast cancer showed an upward trend both in China and globally,with a particularly pronounced increase in elderly male.The disease burden of elderly breast cancer in China is expected to continue increasing in the future,necessi-tating strengthened primary and secondary prevention measures,as well as optimized screening programs for the elderly population to reduce disease risks and improve prognosis.

Objective To investigate changes in gut microbiota during diabetic nephropathy(DN)pro-gression using 16S rDNA sequencing technology.Methods A total of 90 male SD rats were randomly divided into a normal control group(n=10,no modeling,regular feeding)and a model group(diabetes model).The diabetes model was established by a single intraperitoneal injection of streptozotocin(STZ)at 60 mg/kg,with regular feeding.According to the feeding time after modeling,the rats were divided into 2-week,4-week,8-week,and 12-week model groups(fed for 2,4,8,and 12 weeks after model establishment),with 20 rats in each group.Blood urea nitrogen(BUN)was measured using the urease method,serum creatinine(Scr)was deter-mined by the picric acid method,and ELISA was used to detect urinary kidney injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)levels.HE,PAS,and Masson staining were used to observe renal tissue pathological changes.Gut microbiota was collected from the rats,and 16S rDNA gene sequencing was used to analyze the gut microbiota to understand changes in the gut microbiota.Results Compared with the normal control group,the levels of KIM-1 and NGAL in urine of rats in all model groups were significantly increased(P<0.05).Pathological staining results showed that,compared with the normal control group,rats in all model groups exhibited diffuse thickening of the glomerular basement membrane and pathological chan-ges such as local necrosis and vacuolar degeneration in renal tubular epithelial cells.16S rDNA sequencing re-sults indicated that the abundance and structure of intestinal microbiota in rats of all model groups changed.Compared with the normal control group,in the 8-week and 12-week model groups,the relative abundance of Bacteroides and Akkermansia decreased,while the relative abundance of Roseburia,Alloprevotella,Prevotel-laceae-Ga6A1,and Ruminococcaceae UCG-005 increased.Compared with the normal control group,in the 12-week model group,the abundance of Akkermansia decreased and that of Prevotellaceae-NK3B31 increased.Conclusion The abundance and structure of gut microbial community in DN rats under conventional feeding at different time points change significantly,further confirming the"gut-kidney axis"theory.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

The nuclear magnetic resonance (NMR) thermal control subsystem described in this paper is a newly developed platform-based thermal management solution. It presents critical challenges in system architecture design and core component selection. Therefore, it is necessary to carry out sufficient reliability design and verification work in the design and development stage to ensure its high quality and high reliability. Firstly, based on the statistical and analytical calculation of the client installation data of the benchmark product, the reliability metric of the new research subsystem is determined, and its usage and environmental profile are defined. Secondly, for the reliability metric to be verified, the test based on reliability growth and reliability demonstration is planned and implemented. A customized test platform is built, relevant reliability test parameters are designed, and a long-term test monitoring and recording mechanism is established to ensure the high-quality implementation of reliability tests. Finally, a detailed analysis is carried out on the design defects and failure modes exposed during the reliability test, and corresponding control measures are proposed to achieve the engineering goal of improving product robustness throughout its life cycle.
Equipment Design ; Magnetic Resonance Spectroscopy/instrumentation* ; Reproducibility of Results