This paper provides a systematic review of the policies, regulations, and management requirements in the development and use of in vitro diagnostic reagents by healthcare institutions, along with their current implementation status both domestically and internationally, and includes a case analysis of the pilot program at Peking Union Medical College Hospital (PUMCH). The Medical Affairs Department of PUMCH, serving as the leading and operational management unit, established a multi-department collaborative governance structure and developed a full-lifecycle management model encompassing project selection, manufacturing approach determination, regulatory submission and approval, batch production, and clinical implementation. Under this management model, the hospital successfully completed five projects within just one year, achieving the highest number of project filings nationwide. Economic benefit evaluation of the first approved reagent, which is urgently required by clinical practice and named allergen-specific immunoglobulin E detection assay for Fraxinus pennsylvanica pollen, demonstrates that the project realized controllable risk and predictable commercial value, and proves that proactive implementation of systematic management model and project systematic construction is the key to successfully advancing laboratory-developed test programs. The experiences provide both theoretical insights and practical guidance for peer medical institutions seeking to develop and implement self-developed in vitro diagnostic reagents.

Objective To assess the efficacy and safety of Tiaozhou Ziyin(TZZY)recipe for treatment of premature ovarian insufficiency(POI)and explore the possible mechanisms.Methods We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets,which were verified by Western blotting.We tested the efficacy and safety of the recipe in 60 POI patients,who were randomized into control group(n=30)with Femoston treatment and TZZY group(n=30)with additional TZZY recipe treatment for 3 menstrual cycles.Results The core active ingredients of TZZY recipe included kaempferol,β-sitosterol,luteolin,and quercetin.The core targets included SRC,TP53,STAT3,PIK3CA,and MAPK3,which were involved in positive regulation of cell movement and protein phosphorylation,the cancer pathways and the PI3K-Akt signaling pathway.Molecular docking showed that the core active ingredients had good binding ability with the core targets.In female rat models of POI,TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins.In the clinical trial,treatment with Femoston and Femoston plus TZZY recipe both significantly increased E2 levels and reduced FSH and LH levels and Kupperman scores of the patients,and the combined treatment produced significantly stronger effects.Both treatments increased the number of antral follicles of the patients,but the combined treatment also significantly increased the levels of AMH.Conclusion The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients,multiple therapeutic targets and multiple pathways,and activating the PI3K/Akt pathway is one of its main mechanisms of action,to improve ovarian reserve function,alleviate clinical symptoms,and enhance clinical efficacy in POI patients.

Objective:To study the changes of immune cells in allergic airway inflammation induced by house dust mites(HDM)in the mouse model,and investigate the effect of alveolar macrophages(AM)on allergic airway inflammation.Methods:Al-lergic airway inflammation was induced by intratracheal injection of HDM,and AM were specifically depleted by intratracheal injec-tion of chlorophosphonate liposomes(CL)before HDM treatment;the immune cells of mouse lung were isolated by heart perfusion.The immune cells of mouse alveolar lavage fluid were isolated by tracheal lavage.The level of type Ⅱ cytokines in alveolar lavage fluid was determined by ELISA.The changes of immune cells in mouse lung tissue and alveolar lavage fluid were detected by flow cytome-try;HE staining and PAS staining were performed to observe the infiltration of inflammatory cell,goblet cell proliferation and mucus secretion in the lung sections after HDM treatment.Results:The effector cells of type Ⅱ immune response,such as group 2 innate lymphoid cells(ILC2)and eosinophils,were significantly increased in allergic airway inflammation induced by HDM in mice.Histo-logical analysis also revealed substantial inflammatory cell infiltration,goblet cells proliferation and mucus secretion in lung tissue.The depletion of AM alleviated HDM induced type Ⅱ immune response,but promoted the infiltration of neutrophils and aggravated the pathological injury of the lung.Conclusion:AM plays an important role in HDM induced allergic airway inflammation.

OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu De-coction,and cell proliferation and migration abilities were assessed.Forty-two BALB/c nude mice were randomly divided into a blank control group,model group,5-fluorouracil(5-FU)group(0.025 g·kg-1),Anzheng Kangliu Decoction low-dose group(7.67 g·kg-1),medium-dose group(15.34 g·kg-1),and high-dose group(30.68 g·kg-1).The inhibitory effect of Anzheng Kan-gliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight,tumor volume,tumor mass,HE staining,im-munohistochemical staining of Ki67 and other indicators.High-throughput transcriptome sequencing was performed to identify differen-tially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group,elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer.Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention.Western blot was employed to detect the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,hexokinase 2(HK2),and lactate dehydrogenase A(LDHA)in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.RE-SULTS In vitro cell experiments demonstrated that,compared with the blank control group,Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells(P<0.01),reduced glucose consumption and lactate production(P<0.05,P<0.01),and downregulated the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).In vivo animal experiments revealed that,compared with the model group,Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice(P<0.01),increased tumor tissue necrosis,decreased glucose consumption and lactate production in tumor tissues(P<0.05,P<0.01),and reduced the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).CONCLUSION Anzheng Kangliu Decoction exerts an in-hibitory effect on colorectal cancer,and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

The rising prevalence of allergic diseases imposes a significant burden on healthcare resources and socio-economic systems. Allergen testing plays a critical role in the prevention, diagnosis, and treatment of allergic diseases. However, its application in clinical practice still faces numerous challenges. This article reviews the current status of allergen testing in clinical settings and discusses the challenges in managing allergic diseases. Additionally, it provides recommendations for improving medical education on allergen testing and promoting standardized clinical management of allergic diseases.

Objective To investigate the relationship between vitamin D receptor(VDR)gene TaqI rs731236 and BsmI rs1544410 polymorphisms and benign paroxysmal positional vertigo(BPPV),the relationship and clinical significance of BPPV.Methods A total of 263 patients with confirmed BPPV admitted to Dongguan People's Hospital from January 2021 to October 2023 were retrospectively selected,and another 100 healthy subjects in the same period were selected as controls.Single nucleotide polymorphisms(SNPs)at the locus of TaqI rs731236 and BsmI rs1544410 gene locus of the were detected by fluorescence quantitative PCR.Single nucleotide polymorphisms(SNP)at TaqI rs731236 and BsmI rs1544410 were detected by fluorescence quantitative PCR.The genetic balance of TaqI and BsmI genes was tested by Hardy-Weinberg balance.Genotype and allele distribution were compared between the two groups.The correlation between TaqI and BsmI genotype and clinical features of BPPV was analyzed.The risk factors of BPPV were analyzed by Logistic regression.Results Compared with the clinical data of the two groups,the levels of diabetes(22.05%),hypertension(28.90%),blood uric acid(345.38±36.69μmol/L),cholesterol(4.98±0.68mmol/L)and low density lipoprotein(3.48±0.67mmol/L)in BPPV group were significantly higher than those in control group(11.00%,15.00%,328.76±32.24μmol/L,4.36±0.57mmol/L,3.07±0.62mmol/L),and the serum 25(OH)D level(62.78±8.69nmol/L)was significantly lower than that in control group(97.65±9.54nmol/L),and the differences were statistically significant(t/χ2=3.982～33.233,all P<0.05).Hardy-Weinberg test showed that the genotype distribution of the SNP locus of TaqI and BsmI genes conforms s to the law of genetic equilibrium and is representative of the population(χ2=1.406～2.851,all P>0.05).The frequencies of AG genotype(53.99%)and A allele(57.41%)at TaqI rs731236 in BPPV group were significantly higher than those in control group(44.00%,48.00%),while the frequencies of GG genotype(15.59%)at TaqI rs731236 in BPPV group were significantly lower than those in control group(30.00%),the frequencies of CC genotype(32.32%)and C allele(54.56%)at BsmI rs1544410 locus in BPPV group were significantly higher than those in control group(18.00%,38.00%),while the frequencies of TT genotype(23.19%)and T allele(45.44%)at BsmI rs1544410 locus were significantly lower than those in control group(42.00%,62.00%),and the differences were statistically significant(χ2=9.589,5.185;14.603,15.900,all P<0.05).BPPV patients carrying AG and AA genotypes at TaqI rs731236 and CT and CC genotypes at BsmI rs1544410 had higher blood uric acid and cholesterol levels and lower serum 25(OH)D levels,and the differences were statistically significant(t=4.256～12.742,all P<0.05).The AG genotype and A allele at TaqI rs731236,CC genotype and C allele at BsmI rs1544410 were one of the independent risk factors for BPPV(Wald χ2=8.651,7.269;5.010,6.793,all P<0.05).Conclusion Carrier of AG genotype and A allele at TaqⅠ rs731236 and CC genotype and C allele at BsmI rs1544410 are closely associated with blood uric acid,cholesterol and serum 25(OH)D levels,and insrease the risk of BPPV.The polymorphism of VDR gene is an independent risk factor for BPPV.

OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

Objective To analyze the distribution characteristics of the single nucleotide polymorphism (SNP) site rs76206423 in the promoter region of the interleukin-2 receptor (IL-2R) β gene among Han males in a high radiation background area (HBRA) in Yangjiang City. Methods A total of 48 male participants from Tangkou Town, Yangxi County, Yangjiang City (HBRA group), and 51 male participants from Hengpo Town, Enping City (control group) were selected as the research subjects using the random number table method. Peripheral venous blood samples of participants from both groups were collected, and genomic DNA was extracted. The genotyping and allele frequency distribution of the rs76206423 (A/G) site in the IL-2R β promoter region was detected among the participants in both groups using the SNP detection method. The difference of allele frequencies between population in HBRA group and five area of East Asia, South Asia, Africa, Europe, and the Americas published in the Human Genome Project database from National Center for Biotechnology Information were analyzed. Results The allele frequencies of rs76206423 of population in both groups conformed to Hardy-Weinberg equilibrium (P>0.05). In the HBRA group, the AA genotype was predominant (64.6%), while the AG genotype was the most common in the control group (51.0%), with a significant difference (P<0.05). Population in both groups showed a predominance of the variant allele A (78.1% and 72.5%, respectively), with no significant difference (P>0.05). The frequency of the G allele of rs76206423 in the population in HBRA group was higher than those in South Asian, African, European, and American populations (all P<0.01), but showed no significant difference compared with East Asian populations (P>0.05). Conclusion In the Han male population from the HBRA in Yangjiang City, the rs76206423 site in the IL-2R β gene promoter region is predominantly composed of the wild-type A allele and AA genotype, indicating genetic stability and a relatively high degree of variation at this locus.