[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective:To compare the spermatogenes response of human chorionic gonadotropin(HCG)combined with human menopausal gonadotropin(HMG)in patients with idiopathic hypogonadotropic hypogonadism(IHH)and congenital combined pituitary hormone deficiency(CCPHD), and to explore related factors.Methods:Clinical data of 90 IHH patients and 61 CCPHD patients from January, 2014 to November, 2018 were retrospectively analyzed. Spermatogenesis was compared between the two groups receiving combined gonadotropin therapy. The patients were then divided into two subgroups: spermatogenesis subgroup and nonspermatogenesis subgroup. Related factors of spermatogenesis after the combined gonadotropin therapy were investigated.Results:After the combined treatment of HCG/HMG for 3, 6, and 9 months, the patients with CCPHD revealed lower testicular sizes than those with IHH( P=0.004, 0.021 and 0.032, respectively). Compared with IHH patients, CCPHD patients had larger testicular volume increments( P<0.001), higher spermatogenesis rates( P=0.048), and shorter initial time for sperm appearance( P<0.001)after 24-month treatment. Multivariate logistic regression analysis showed that lower total cholesterol(TC)(IHH group: OR=5.508, 95% CI 1.110-27.326, P=0.037; CCPHD group: OR=4.068, 95% CI 1.077-15.371, P=0.039)was an independent risk factor of poorer spermatogenesis in patients with IHH and CCPHD. Conclusions:The patients with CCPHD demonstrate a better response to combined gonadotropin treatment than those with IHH. Lower TC is an independent risk factor for poor spermatogenesis of combined HCG/HMG therapy in patients with IHH or CCPHD.

Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.

ObjectiveTo investigate the social support status and influencing factors of schizophrenics in remission in Northeast Sichuan， and to provide ideas for improving their social support. MethodsFrom May to September 2020， a total of 533 patients who met the diagnosis criteria of the International Classification of Diseases， tenth edition （ICD-10） for schizophrenics in remission at the mental health institutions in Guangyuan， Bazhong and Dazhou cities were selected for the survey， and patients were assessed by self-made demographic and clinical data inventory and Social Support Rating Scale （SSRS）. Then the social support status of schizophrenic in remission and influencing factors were analyzed， meantime， the impact of the second round reimbursement policy of medical insurance benefits on their social support was addressed particularly. Results①The SSRS total score， objective support， subjective support， and utilization of support scores of schizophrenics in remission were lower than those of the national norm （t=5.065~30.382， P<0.01）. ②Univariate analysis showed that SSRS score was relatively high among patients with female gender （t=-3.632）， retired status （F=5.951）， married status （F=5.951）， spouse as primary caregiver （F=23.841）， annual household income >5 000 yuan （F=15.892）， patient's economic income （t=4.083）， and outpatient or online follow-up （F=3.954）， with statistically significant differences （P<0.05 or 0.01）. ③The total and dimensional scores of SSRS in patients with access to the second round medical insurance reimbursement were significantly higher than those without （t=10.195~25.103， P<0.01）. ④Multiple linear regression analysis denoted that gender， work status， marital status， primary caregivers， annual family income， economic income， follow-up visits and the second round medical insurance reimbursement were the factors influencing social support status of schizophrenics in remission （β=0.201~2.115， P<0.05 or 0.01）. ConclusionThe social support of schizophrenics in remission in Northeast Sichuan is below the national average， furthermore， their social support levels are affected by the gender， work status， marital status， primary caregivers， annual family income， economic income， follow-up visits and the second round medical insurance reimbursement， and the second round medical insurance reimbursement may ameliorate the social support status of patients.

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

OBJECTIVE: To analyze the clinical symptom and parental origin of patients with MECP2 duplication syndrome in order to provide a basis for genetic counseling and prenatal diagnosis. METHODS: Clinical symptoms of four patients who were diagnosed with MECP2 duplication syndrome by copy number variation sequencing (CNV-Seq) were reviewed. The maternal origin of the duplications were verified. RESULTS: All patients were males, and CNV-Seq revealed that they have all harbored a duplication in the Xq28 region spanning 0.32 ~ 0.86 Mb, which were derived from asymptomatic mothers. The clinical symptoms of three patients with three copies included delayed speech, intellectual disability, and muscular hypotonia, while the patient with four copies had died at 6 months after birth, with clinical symptoms including recurrent infections, seizures, and spasticity. CONCLUSION The four cases of MECP2 duplication syndrome have shown complete penetrance and have all derived from asymptomatic mothers. As a stable and reliable method, CNV-Seq can accurately detect the MECP2 duplication syndrome.
Chromosomes, Human, X ; DNA Copy Number Variations ; Gene Duplication ; Humans ; Male ; Mental Retardation, X-Linked ; Methyl-CpG-Binding Protein 2/genetics* ; Phenotype