Objective: To develop a RHCE genotyping assay based on kompetitive allele-specific PCR (KASP) and assess its clinical accuracy for RhCE blood group determination. Methods: KASP primers were designed to interrogate three RHCE loci: the 109 bp insertion/deletion in intron 2, c. 307T>C, and c. 676C>G. A total of 1 194 RhD-positive inpatients from Chengdu were typed by both KASP genotyping and manual tube serology. Discordant samples (n=10) were retested by both methods and further resolved by Sanger sequencing. An additional 377 cases were tested for the c. 48C>G locus to evaluate the predictive accuracy of individual loci and combined locus testing for RhC antigen. Results: Genotyping concordance with serology was 100.0% for both the c. 676C>G locus (RhE/Rhe) and the c. 307T>C locus (Rhc). For RhC prediction using the 109 bp insertion, overall accuracy was 99.7% (1 191/1 194); the 3 discordant cases were confirmed by Sanger sequencing to be false negatives attributable to 109 bp deletion in intron 2. Testing the c. 48C>G allele for RhC prediction yielded 7 false positives, with an accuracy of 98.1% (370/377). RhC antigen status was determined by combining the 109 bp insertion and the c. 48C allele. After excluding 10 samples with inconsistent results between the two loci, the accuracy reached 100% in the remaining 367 samples. When both loci were applied in combination, accuracy reached 100% in the 367 cases with concordant results. Among the 1 194 patients, CCee (45.8%) and CcEe (31.7%) were the most common RhCE phenotypes. The e antigen had the highest positivity rate (92.2%), and the Ce haplotype was the most frequent (66.9%). Conclusion: The KASP-based RHCE genotyping method achieves high accuracy for clinical RhCE typing. Combining the 109 bp insertion/deletion with the c. 48C allele significantly improves RhC antigen prediction compared with either locus alone. This method was applied to RhCE genotyping of 1 194 RhD-positive inpatients in Chengdu, providing local RhCE phenotype and haplotype distribution data to support RhCE-matched transfusion practice.

Background In recent years, the increasingly widespread application of nuclear and medical radiation technologies has resulted in a large number of occupational populations exposed to low-dose ionizing radiation (LDIR). At present, there is no consistent conclusion on the effects of long-term exposure to LDIR on the metabolic health of the occupational population. Objective To explore the association between long-term exposure to LDIR and metabolic syndrome (MetS) among medical radiologists. Methods A cross-sectional study was conducted to enroll 6431 medical radiologists who ordered occupational health checkups from January 2022 to December 2023, and basic information such as demographic characteristics, occupational characteristics, lifestyles, and dietary habits was collected through questionnaires. Physical examinations were conducted using a standardized protocol. Individual dose equivalents of occupational external exposure were monitored by dosimeters worn by medical radiologists. Logistic regression model was used for identifying influencing factors of MetS and sensitivity analysis, and restricted cubic spline model was used to explore the dose-response relationship between cumulative effective dose and MetS. Two-stage linear regression was used to evaluate threshold effect of association between cumulative effective dose and MetS. Results The positive rate of MetS was 13.6% (877/6431) among the enrolled 6431 study participants. The logistic regression showed that gender, age, monthly income, body mass index (BMI), cumulative effective dose, and smoking were influencing factors for MetS. The risk of MetS was higher in males (OR=1.511, 95%CI: 1.209, 1.888); using the < 30 years old group as reference, the risk of MetS was higher in the 30-39 years old (OR=1.509, 95%CI: 1.095, 2.079), 40-49 years old (OR=2.214, 95%CI: 1.551, 3.161), and ≥50 years old (OR=3.480, 95%CI: 2.338, 5.181) groups; using the <10000 yuan group as reference, the risk of MetS was lower in the group with a monthly income of 10000-14999 yuan (OR=0.715, 95%CI: 0.582, 0.878); the risk of MetS was higher in the BMI ≥ 24 kg·m⁻² group (OR=7.548, 95%CI: 6.223, 9.156); using the < 0.76 mSv group as reference, the risk of MetS was higher in the cumulative effective dose of 0.76-2.73 mSv group (OR=1.270, 95%CI: 1.017, 1.586); the risk of MetS was higher in the smoking group (OR=1.734, 95%CI: 1.428, 2.107). The results of restricted cubic spline showed that the cumulative effective dose was nonlinearly correlated with MetS (P _{non-linearity}=0.028), with an inflection point of 1.25 mSv. The risk of developing MetS increased by 34.1% for each unit increase in cumulative effective dose up to 1.25 mSv, whereas above 1.25 mSv, the statistical association was not significant. The sensitivity analysis results showed that after excluding the self-reported hypertensive and diabetic patients, the cumulative effective dose 0.76-2.73 mSv group still had an increased risk of developing MetS compared with the < 0.76 mSv group (P < 0.05), and the results were robust. Conclusion Among medical radiologists, male, age, BMI, and smoking are positively correlated with MetS, and monthly income is negatively correlated with MetS; cumulative effective dose is non-linearly correlated with MetS among medical radiologists.

OBJECTIVE To explore the prevalence of Ureaplasma urealyticum and Mycoplasma hominis among the patients with chronic cervicitis(CC)and observe their drug resistance to commonly used antibiotics.METHODS A total of 91 patients with CC who were treated in gynecology department of Women and Children's Hospital Affiliated to Ningbo University from Jan.2022 to Jun.2024 were assigned as the CC group,meanwhile,91 healthy women who received physical examination were chosen as the control group.The genital tract secretions were collected from all of the research subjects for the culture of U.urealyticum and M.hominis and drug suscep-tibility testing.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis were com-pared between the two groups.The isolation rates of U.urealyticum and M.hominis were compared among the different age groups of CC patients.The drug susceptibility testing of U.urealyticu m and M.hominis for doxycyc-line(DOX),josamycin(JOS),ofloxacin(OFL),clarithromycin(CLA),erythromycin(ERY),tetracycline(TET),azithromycin(AZI)and pristinamycin(PTN)were observed.RESULTS Totally 75(82.41％)genital tract secretion samples tested positive for Mycoplasma among the 91 samples,37 detected with U.urealyticum,25 were M.hominis,and 13 were U.urealyticum plus M.hominis.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis of the CC group were 40.66％,24.47％and 14.29％,respective-ly,higher than 8.79％,4.40％and 5.49％of the control group(P＜0.05).The total detection rate of U.urealyti-cum,M.hominis and U.urealyticum plus M.hominis was higher among the CC patients aged between 20 and 40 years old than among the CC patients aged more than 40 years old(P＜0.05).The U.urealyticum strains from the positive specimens of the CC patients were highly sensitive to CL A and DOS but were resistant to OFL,CIP and PTN;the M.honinis and U.urealyticum plus M.hominis strains were sensitive to JOS and DOX but were resistant to OFL and CIP.CONCLUSIONS The detection rates of U.urealyticum plus M.hominis are higher a-mong the CC patients than among the normal population.The isolated U.urealyticum and M.hominis strains are highly resistant to quinolones and aminoglycosides.It is necessary for the hospital to empirically choose sensitive antibiotics based on the result of drug susceptibility testing.

Kidney transplantation is the best renal replacement therapy for patients with end-stage renal disease. However, it faces significant challenges due to a critical shortage of donor organs and the underutilization of expanded standard donor (ESD) kidneys.Dual kidney transplantation can increase the utilization of expanded standard donor kidneys and enlarge the donor pool, which is an effective solution to deal with kidney shortage. This review provides a systematic presentation of the current status of research on allocation and recipient selection, surgical technique, complications, postoperative efficacy and immunosuppression protocols for adult dual kidney transplantation, with the aim of providing assistance in clinical practice.

OBJECTIVE To explore the prevalence of Ureaplasma urealyticum and Mycoplasma hominis among the patients with chronic cervicitis(CC)and observe their drug resistance to commonly used antibiotics.METHODS A total of 91 patients with CC who were treated in gynecology department of Women and Children's Hospital Affiliated to Ningbo University from Jan.2022 to Jun.2024 were assigned as the CC group,meanwhile,91 healthy women who received physical examination were chosen as the control group.The genital tract secretions were collected from all of the research subjects for the culture of U.urealyticum and M.hominis and drug suscep-tibility testing.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis were com-pared between the two groups.The isolation rates of U.urealyticum and M.hominis were compared among the different age groups of CC patients.The drug susceptibility testing of U.urealyticu m and M.hominis for doxycyc-line(DOX),josamycin(JOS),ofloxacin(OFL),clarithromycin(CLA),erythromycin(ERY),tetracycline(TET),azithromycin(AZI)and pristinamycin(PTN)were observed.RESULTS Totally 75(82.41％)genital tract secretion samples tested positive for Mycoplasma among the 91 samples,37 detected with U.urealyticum,25 were M.hominis,and 13 were U.urealyticum plus M.hominis.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis of the CC group were 40.66％,24.47％and 14.29％,respective-ly,higher than 8.79％,4.40％and 5.49％of the control group(P＜0.05).The total detection rate of U.urealyti-cum,M.hominis and U.urealyticum plus M.hominis was higher among the CC patients aged between 20 and 40 years old than among the CC patients aged more than 40 years old(P＜0.05).The U.urealyticum strains from the positive specimens of the CC patients were highly sensitive to CL A and DOS but were resistant to OFL,CIP and PTN;the M.honinis and U.urealyticum plus M.hominis strains were sensitive to JOS and DOX but were resistant to OFL and CIP.CONCLUSIONS The detection rates of U.urealyticum plus M.hominis are higher a-mong the CC patients than among the normal population.The isolated U.urealyticum and M.hominis strains are highly resistant to quinolones and aminoglycosides.It is necessary for the hospital to empirically choose sensitive antibiotics based on the result of drug susceptibility testing.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

The CyberKnife, an acronym for the stereotactic radiosurgery platform, represents an image-guided stereotactic radiotherapy technique. This technology precisely delivers ionizing radiation to tissues, effectively damaging tumor cells, and is suitable for radiotherapy of both intracranial and extracranial tumors. This article reports the first performance of CyberKnife by radiotherapy at Peking Union Medical College Hospital, including a patient with uncontrolled pituitary adenoma after surgery and radiotherapy, and another patient with vertebral metastasis following targeted therapy for lung adenocarcinoma. The application of CyberKnife technology in radiotherapy has achieved highly accurate dose delivery, enabling targeted irradiation of tumor lesions while minimizing damage to surrounding normal tissues, thereby yielding relatively ideal clinical outcomes.

Kidney transplantation is the best renal replacement therapy for patients with end-stage renal disease. However, it faces significant challenges due to a critical shortage of donor organs and the underutilization of expanded standard donor (ESD) kidneys.Dual kidney transplantation can increase the utilization of expanded standard donor kidneys and enlarge the donor pool, which is an effective solution to deal with kidney shortage. This review provides a systematic presentation of the current status of research on allocation and recipient selection, surgical technique, complications, postoperative efficacy and immunosuppression protocols for adult dual kidney transplantation, with the aim of providing assistance in clinical practice.