OBJECTIVE To explore a synergistic medication strategy integrating stage-specific modifications of Bushen huoxue decoction with hormone replacement therapy （HRT） for premature ovarian insufficiency （POI）. METHODS The connotation of Academician Tong Xiaolin’s “state-target differentiation and treatment” theory and the disease stage characteristics of POI were summarized. The latent stage， subclinical stage， clinical stage and exhaustion stage of POI were classified into corresponding core pathogenesis “states” and key objective indicator “targets”. Taking Bushen huoxue decoction as the basic prescription， its staged modification scheme and its sequential combination with HRT were analyzed. RESULTS & CONCLUSIONS The four stages of POI correspond to four pathogenic states respectively： kidney yin deficiency， kidney deficiency and blood stasis， heart-kidney disharmony， and deficiency of both yin and yang. Follicle-stimulating hormone （FSH）， anti-Müllerian hormone （AMH）， antral follicle count （AFC） and Kupperman score were taken as the evaluation targets of staging. Combined with the “state-target” characteristics of each stage， a medication principle based on Bushen huoxue decoction with syndrome differentiation modification and stage-adjusted administration was established： traditional Chinese medicine dominates in the latent stage， a sequential collaborative regimen is adopted in the subclinical stage， HRT is dominant supplemented by traditional Chinese medicine in the clinical stage， and integrated traditional Chinese and Western medicine is applied to consolidate the root cause in the exhaustion stage.

OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

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.

To summarize the perioperative nursing experience of a patient with thoracic and abdominal aortic dissection aneurysm after Stanford type A aortic dissection surgery,who underwent intra-abdominal aortic aneurysm endovascular isolation,in situ fenestration branch covered stent placement,and artificial blood vessel bypass.The nursing points include regular evaluation of the intra-abdominal pressure of the patient,being on guard against the rupture of the dissection;specialist nurses participated in the preoperative multidisciplinary discussion;establishing an emergency plan for the rescue of ruptured aortic dissection;monitoring the vital signs of patients closely to prevent critical complications during surgery.After multidisciplinary treatment and meticulous care,the patient's surgery went smoothly and the postoperative recovery was good.The patient was discharged 8 days later.

Objective:To construct a meridian tapping exercise program for frail elderly, so as to provide daily healthcare options for frail elderly people.Methods:Guided by the theory of meridians and collaterals, data mining was conducted on the database of ancient Chinese medical literature to select acupoints and meridians for tapping. Through literature research, the exercise prescription was improved. A preliminary exercise prescription was formulated through literature review and revised through two rounds of expert consultation in December 2023.Results:The effective response rate for both rounds of expert consultation questionnaires was 7/7. The expert authority coefficients were 0.83 and 0.87, respectively, and the overall Kendall′s coefficient of concordance was 0.301 and 0.302 (both P<0.05). The final meridian tapping exercise for frail elderly comprised 2 primary indicators, 8 secondary indicators, and 23 tertiary indicators. Conclusions:The meridian tapping exercise for the frail elderly is scientific, reliable and practical, which can provide a choice for the frail elderly to carry out targeted traditional Chinese medicine exercises.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

Gastrointestinal polyposis syndromes are primarily characterized by multiple polyps in the gastrointestinal tract, with their pathogenic mechanisms largely related to genetic factors and involving multiple signaling pathways. Adenomatous polyposis syndromes are mainly associated with APC gene variants, while some cases may arise from MUTYH gene variants. Peutz-Jeghers syndrome is primarily linked to STK11 gene variants. Juvenile polyposis syndrome is mainly associated with variants in the SMAD4 and BMPR1A genes. PTEN hamartoma tumor syndrome is predominantly caused by PTEN gene variants. Hereditary mixed polyposis syndrome is primarily related to variants of the GREM1 and BMPR1A genes. This article systematically summarizes the advance in genetics research on Gastrointestinal polyposis syndromes to enhance clinicians′ understanding of these diseases and improve their diagnostic and therapeutic approaches.

Objective:To explore the application effect of nursing coordination process based on healthcare failure mode and effect analysis (HFMEA) management in the treatment of patients with acute ST-segment elevation myocardial infarction (STEMI), so as to improve clinical treatment efficiency.Methods:In this prospective cohort study, STEMI patients requiring emergency percutaneous coronary intervention (PCI) admitted to the Department of Emergency, Subei People′s Hospital of Jiangsu Province from January to May 2024 were selected by random sampling method. According to the admission time, patients were divided into control group (from January to February 2024, received routine emergency process) and experimental group (from April to May 2024, received nursing coordination process based on HFMEA management). The triage evaluation time, reception time, reporting time of the first electrocardiogram, coming out time of troponin T results, improvement time of preoperative preparation, treatment effect (length of hospital stay, success rate of treatment, nosocomial mortality) and emergency physicians′ satisfaction with nursing work in the two groups were compared.Results:In the 100 STEMI patients, there were 48 cases in the control group, with 23 males and 25 females, aged (61.64 ± 4.37) years old. There were 52 cases in the experimental group, with 26 males and 26 females, aged (62.11 ± 4.61) years old. The triage evaluation time, reception time, reporting time of the first electrocardiogram, coming out time of troponin T results and improvement time of preoperative preparation in the experimental group were (1.65 ± 0.57), (2.46 ± 0.57), (7.58 ± 1.32), (16.43 ± 2.16), (46.18 ± 3.94) min, shorter than (2.48 ± 0.69), (3.41 ± 0.63), (10.69 ± 1.24), (18.66 ± 2.37), (54.37 ± 4.11) min in the control group, the differences were statistically significant ( t values were 4.92-12.12, all P<0.05). The length of hospital stay and nosocomial mortality in the experimental group were (10.16 ± 2.34) d, 3.85% (2/52), lower than (12.38 ± 2.09) d, 16.67% (8/48) in the control group, and success rate of treatment was 90.38% (47/52), higher than 75.00% (36/48) in the control group, the differences were statistically significant ( t=4.99, χ2=4.56, 4.19, all P<0.05). The emergency physicians′ satisfaction with nursing work in the experimental group was (79.43 ± 6.00) points, higher than (64.44 ± 6.54) points in the control group, the difference was statistically significant ( t=11.95, P<0.05). Conclusions:Nursing coordination process based on HFMEA management can effectively improve emergency efficiency in STEMI patients, shorten emergency time and reduce nosocomial mortality.

Objective:The SARS-CoV-2 has a high natural mutation rate, and dynamic monitoring of virus variants remains a key focus in current COVID-19 prevention and control efforts.Methods:In this study, a sensitive and rapid method for detecting SARS-CoV-2 omicron variant nucleic acid was established based on the BMD-PCR technology.Results:This method showed good specificity, and had no cross-reactivity with 11 common viruses transmitted via the respiratory and gastrointestinal tracts, and the limit of detection is 555 copies/ml. Compared with SARS-CoV-2 whole-genome sequencing result, among 50 samples with original Ct values ≤32 tested for the Omicron variant, 49 samples tested positive for the N679K mutation site using BMD-PCR Omicron variant detection, achieving a concordance rate of 98.00%. For 30 samples JN.1 lineage, 29 samples tested positive for the K356T mutation site using BMD-PCR JN.1 lineage detection, with a concordance rate of 96.67%. For 10 samples with original SARS-CoV-2 detection Ct values between 35 and 32, 7 samples tested positive for the N679K mutation site using BMD-PCR Omicron variant detection, Resultsing in a detection rate of 70.00%. For samples with SARS-CoV-2 nucleic acid detection Ct values>35, the detection rate for the N679K mutation site in the BMD-PCR Omicron variant was 20.00%.Conclusions:This method can serve as a high-throughput supplementary approach for the preliminary identification of SARS-CoV-2 variant genotypes.

Objective:To investigate the efficacy of deep transcranial magnetic stimulation combined with fluoxetine therapy in the treatment of depression in adolescent patients and its effects on the hypothalamic-pituitary-adrenal axis.Methods:A randomized controlled study was conducted, enrolling 108 adolescent patients with depression diagnosed and treated at The Third Hospital of Quzhou from May 2022 to April 2023. The participants were randomly assigned to an observation group and a control group, with 54 patients in each group. The control group received fluoxetine hydrochloride capsules, while the observation group received deep transcranial magnetic stimulation in addition to the treatment provided to the control group. Both groups underwent a treatment course of 4 weeks. The scores of the Hamilton Depression Rating Scale scores and the World Health Organization Quality of Life-BREF were compared before and after treatment. Serum levels of corticotropin-releasing hormone, cortisol, and adrenocorticotropic hormone were measured before and after treatment. Additionally, the expression levels of cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-6 in peripheral blood cells were also detected using western blot assay. The specific regulatory signaling pathways involved in the combined treatment was investigated using transcriptome sequencing.Results:At 2 and 4 weeks after treatment, the Hamilton Depression Rating Scale scores in the observation group [(15.62 ± 1.64), (9.56 ± 1.19)] were significantly lower than those in the control group [(16.69 ± 1.89), (13.47 ± 1.16), t = 3.14, 17.29, both P < 0.01]. The scores of the physiological, psychological, social, and environmental domains in the the World Health Organization Quality of Life-BREF in the observation group were significantly higher than those in the control group ( t = -5.06, -3.86; -2.17, -3.26; -1.99, -2.15; -2.02, -3.55, all P < 0.05). After 4 weeks of treatment, serum levels of cortisol, corticotropin-releasing hormone, and adrenocorticotropic hormone in the observation group were (8.97 ± 2.26) mmol/L, (86.33 ± 13.76) ng/L, and (8.69 ± 2.98) mmol/L, respectively. These values were significantly lower than those in the control group, which were (13.06 ± 2.91) mmol/L, (97.41 ± 15.58) ng/L, and (12.77 ± 3.06) mmol/L ( t = 13.73, 16.75, 36.21, all P < 0.001). The levels of cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha in peripheral blood in the observation group were significantly lower than those in the control group ( t = 8.16, 3.92, 6.16, all P < 0.001). Furthermore, tumor necrosis factor-α levels were positively correlated with serum levels of corticotropin-releasing hormone, cortisol, and adrenocorticotropic hormone ( r = 0.803, 0.846, 0.879, all P < 0.05). Transcriptome sequencing results showed that inflammatory response was a specific regulatory pathway involved in the combined therapy. Conclusions:Deep transcranial magnetic stimulation combined with fluoxetine therapy can effectively improve the clinical symptoms of adolescent patients with depression and further regulate the hypothalamic-pituitary-adrenal axis and micro-inflammatory state. Therefore, this combined therapy is of great clinical application value.