Objective: To characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

Objective:To develop an indicator system for defining the health services provided by family doctors within the "Healthy Subdistrict" initiative in China.Methods:An initial set of indicators was developed through literature review and qualitative research, followed by the design of an expert consultation questionnaire. Twenty-one experts with extensive experience in community family doctor services in Beijing were selected. Two rounds of Delphi consultations were conducted via email between December 2024 and February 2025. Expert demographics and authority coefficients were collected and the indicator system was finalized.Results:The response rate was 100% for both rounds. The average expert authority coefficient ( Cr) was 0.860 (range: 0.700-1.000). Kendall′s W for importance and feasibility increased from 0.129 and 0.196 in the first round to 0.230 and 0.268 in the second round (all P<0.001), indicating strong consensus. The final system includes 5 first-level and 23 second-level indicators, categorized as: Integrated Preventive and Clinical Care Services, Healthy Community Promotion Services, Basic Medical Services, Public Health Services, and Services for Promoting Equity in Citizen Health and Well-being. The highest-weighted first-level indicators were Basic Medical Services (0.281) and Integrated Preventive and Clinical Care Services (0.281), followed by Services for Promoting Equity in Citizen Health and Well-being (0.191), Healthy Community Promotion Services (0.124), and Public Health Services (0.124). All indicators had importance and feasibility scores above 3.5. Conclusion:This study establishes a weighted indicator system to guide and evaluate the health services provided by family doctors within the "Healthy Subdistrict" initiative, clarifying key service priorities.

Objective To explore the challenges faced by online appointment nurses during nasogastric intubation and to provide a reference for improvement of the quality and safety of the services provided by online appointment nursing.Methods A purposive sampling was employed to select 13 online appointment nurses from our hospital who had previously provided home nasogastric intubation services for patients.Semi-structured interviews were conducted with the online appointment nurses.The results acquired from the interviews were analysed using Colaizzi's method.Results Two themes were identified.Theme 1 covered the increased risks of nasogastric intubation due to the patients themselves and home environment,which included 4 sub-themes of difficulties in identification and response due to complex conditions of patient,high risk of a sudden asphyxia with poor resuscitation facility,psychological stress from unfamiliar home environment,and more challenges in risk identification due to limited conditions for performing home-based intubation procedures;Theme 2 covered the coping strategies of online-scheduled nurses,which included the improvement of knowledge and skills in emergency nursing to improve comfidence and judge ability of intubation,the strengthening of nurse-patient communication to build a trust and cooperation,the conduct of thorough assessment to ensure procedural safety,and the use of alternative tools and collaboration with family members.Conclusion Online appointment nurses face challenges and risks from both of the procedures and patients themselves during home based nasogastric intubation.Hospitals and relevant management should actively implement corresponding strategies,provide training and guidance for online appointment nurses,develop relevant regulations,and improve the management mechanisms of the internet platform to ensure the safety of home based nasogastric intubation for online appointment nurses and improve the quality of the"Internet Plus Nursing Services."

Objective:To evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) gene polymorphism on the postoperative analgesic efficacy of alfentanil in patients undergoing radical mastectomy.Methods:In this prospective study, adult female patients diagnosed with breast cancer who underwent surgical treatment at the First Affiliated Hospital of Zhengzhou University were selected as case group ( n=162), while age-matched healthy adult females were selected as control group ( n=80). All subjects had a body mass index of 18-30 kg/m 2. The genotype and allele frequencies of TRPV1 rs8065080 and rs222747 were compared between the two groups, and the consumption of alfentanil and requirement for rescue analgesia within 48 h after surgery were recorded in breast cancer patients with different TRPV1 rs222747 genotypes. Results:Three genotypes of CC, GC, and GG were detected at rs222747 locus of TRPV1 gene, and there was no significant difference in the genotype distribution between the two groups ( P>0.05). Three genotypes of CC, TC and TT were detected at rs8065080 locus of TRPV1 gene, and there was significant difference in the genotype distribution between the two groups ( P<0.05). There was no significant difference in the basic data of patients with different genotypes of TRPV1 gene rs222747 locus ( P>0.05). There were significant differences in the consumption of alfentanil during 0-24 h after surgery and during 24-48 h after surgery and rate of rescue analgesia within 48 h after surgery among patients with different genotypes of TRPV1 gene rs222747 locus ( P<0.05). Conclusions:The polymorphism at the TRPV1 gene rs222747 locus can influence the postoperative analgesic efficacy of alfentanil in breast cancer patients undergoing radical mastectomy, suggesting that genetic factors may be one of the reasons for the inter-individual variability in alfentanil efficacy.

Objective To explore the challenges faced by online appointment nurses during nasogastric intubation and to provide a reference for improvement of the quality and safety of the services provided by online appointment nursing.Methods A purposive sampling was employed to select 13 online appointment nurses from our hospital who had previously provided home nasogastric intubation services for patients.Semi-structured interviews were conducted with the online appointment nurses.The results acquired from the interviews were analysed using Colaizzi's method.Results Two themes were identified.Theme 1 covered the increased risks of nasogastric intubation due to the patients themselves and home environment,which included 4 sub-themes of difficulties in identification and response due to complex conditions of patient,high risk of a sudden asphyxia with poor resuscitation facility,psychological stress from unfamiliar home environment,and more challenges in risk identification due to limited conditions for performing home-based intubation procedures;Theme 2 covered the coping strategies of online-scheduled nurses,which included the improvement of knowledge and skills in emergency nursing to improve comfidence and judge ability of intubation,the strengthening of nurse-patient communication to build a trust and cooperation,the conduct of thorough assessment to ensure procedural safety,and the use of alternative tools and collaboration with family members.Conclusion Online appointment nurses face challenges and risks from both of the procedures and patients themselves during home based nasogastric intubation.Hospitals and relevant management should actively implement corresponding strategies,provide training and guidance for online appointment nurses,develop relevant regulations,and improve the management mechanisms of the internet platform to ensure the safety of home based nasogastric intubation for online appointment nurses and improve the quality of the"Internet Plus Nursing Services."

Objective:To evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) gene polymorphism on the postoperative analgesic efficacy of alfentanil in patients undergoing radical mastectomy.Methods:In this prospective study, adult female patients diagnosed with breast cancer who underwent surgical treatment at the First Affiliated Hospital of Zhengzhou University were selected as case group ( n=162), while age-matched healthy adult females were selected as control group ( n=80). All subjects had a body mass index of 18-30 kg/m 2. The genotype and allele frequencies of TRPV1 rs8065080 and rs222747 were compared between the two groups, and the consumption of alfentanil and requirement for rescue analgesia within 48 h after surgery were recorded in breast cancer patients with different TRPV1 rs222747 genotypes. Results:Three genotypes of CC, GC, and GG were detected at rs222747 locus of TRPV1 gene, and there was no significant difference in the genotype distribution between the two groups ( P>0.05). Three genotypes of CC, TC and TT were detected at rs8065080 locus of TRPV1 gene, and there was significant difference in the genotype distribution between the two groups ( P<0.05). There was no significant difference in the basic data of patients with different genotypes of TRPV1 gene rs222747 locus ( P>0.05). There were significant differences in the consumption of alfentanil during 0-24 h after surgery and during 24-48 h after surgery and rate of rescue analgesia within 48 h after surgery among patients with different genotypes of TRPV1 gene rs222747 locus ( P<0.05). Conclusions:The polymorphism at the TRPV1 gene rs222747 locus can influence the postoperative analgesic efficacy of alfentanil in breast cancer patients undergoing radical mastectomy, suggesting that genetic factors may be one of the reasons for the inter-individual variability in alfentanil efficacy.

Objective:To develop an indicator system for defining the health services provided by family doctors within the "Healthy Subdistrict" initiative in China.Methods:An initial set of indicators was developed through literature review and qualitative research, followed by the design of an expert consultation questionnaire. Twenty-one experts with extensive experience in community family doctor services in Beijing were selected. Two rounds of Delphi consultations were conducted via email between December 2024 and February 2025. Expert demographics and authority coefficients were collected and the indicator system was finalized.Results:The response rate was 100% for both rounds. The average expert authority coefficient ( Cr) was 0.860 (range: 0.700-1.000). Kendall′s W for importance and feasibility increased from 0.129 and 0.196 in the first round to 0.230 and 0.268 in the second round (all P<0.001), indicating strong consensus. The final system includes 5 first-level and 23 second-level indicators, categorized as: Integrated Preventive and Clinical Care Services, Healthy Community Promotion Services, Basic Medical Services, Public Health Services, and Services for Promoting Equity in Citizen Health and Well-being. The highest-weighted first-level indicators were Basic Medical Services (0.281) and Integrated Preventive and Clinical Care Services (0.281), followed by Services for Promoting Equity in Citizen Health and Well-being (0.191), Healthy Community Promotion Services (0.124), and Public Health Services (0.124). All indicators had importance and feasibility scores above 3.5. Conclusion:This study establishes a weighted indicator system to guide and evaluate the health services provided by family doctors within the "Healthy Subdistrict" initiative, clarifying key service priorities.

Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

Objective:To observe and analyze the clinical characteristics of children with autosomal dominant hereditary microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability syndrome (MCLMR).Methods:A retrospective clinical study. In September 2023, the first patient and three family members (parents, brother) of MCLMR who were diagnosed through ophthalmic examination and genetic testing at Department of Ophthalmology of Henan Children's Hospital were included in the study. Clinical data were collected, inquired about medical history and family history in detail, and performed best corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography (FFA), flash visual evoked potential (F-VEP), full field electroretinogram (ERG), cranial magnetic resonance imaging (MRI), and systemic examination. 3 ml of peripheral venous blood were collected from the proband, her parents and younger brother, and extracted whole genome DNA. Second generation sequencing technology was used for gene sequencing. For suspected pathogenic sites, Sanger sequencing was used for validation, and bioinformatics analysis was performed to determine the pathogenicity of the genetic variant sites. The relevant literature of PubMed of the National Library of Medicine and Wan Fang Med Online by computer were searched. The genetic characteristics and conducted literature review were summarized.Results:The proband (Ⅱ-1) was an 8-year-old and 5-month-old female. Her head was relatively small, the lower jaw was small, the ears protrude, the nose was wide, the eyelid was tilted upwards, philtrum was long. Mild intellectual disability, no history of lymphedema. The BCVA values for the right and left eyes were 0.08 and 0.1, respectively. Bilateral nystagmus. Atrophic lesioned in the macular area and below choroid retina of both eyes. FFA examination showed mottled fluorescent staining in the macular area and the below retina, with no obvious fluorescein leakage in the late stage. OCT examination revealed shallow macular fovea morphology, absence of ellipsoidal bands, unclear layers, thinning of the entire retina, and significant atrophy of the choroid and retina beneath the macula. F-VEP examination, no waveform was detected in both eyes. Full field ERG examination showed severe reduction in amplitude of a wave and b wave in both eyes. Head magnetic resonance imaging showed widening of the subarachnoid space in the left temporal region, with no significant abnormal signals observed in the brain parenchyma. Her father (Ⅰ-1) had mild nystagmus and strabismus. The phenotypes of the eyes of the mother (Ⅰ-2) and brother (Ⅱ-2) were not significantly abnormal. The genetic testing results showed that the proband (Ⅱ-1) had a heterozygous missense mutation c.895A>G (p.Ile299Val) in exon 8 of the KIF11 gene, which was a known mutation. Her parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) were both wild-type. The bioinformatics analysis results indicated that this mutation is a potentially pathogenic variant. A total of 109 cases were retrieved from 20 relevant literatures. Among them, 55 were male, 54 were females. There were 61 cases with family history and 48 cases without family history, respectively. Among the 109 cases, 98 cases (89.9%, 98/109) had microcephaly, 2 cases had premature closure of cranial sutures, and 11 patients underwent cranial MRI, which showed 11 cases of small head with simplified development of the cerebral gyrus. 50 cases (45.9%, 50/109) of lymphedema. 83 cases (76.1%, 83/109) of intellectual developmental disorders. 92 cases (84.4%, 92/109) had ocular abnormalities, 69 cases (63.3%, 69/109) had chorioretinopathy, 20 cases (18.3%, 20/109) had retinal folds, 10 cases (9.2%, 10/109) had nystagmus, and 17 cases (15.6%, 17/109) had retinal detachment. Conclusions:The main clinical manifestations of MCLMR are microcephaly, chorioretinopathy, with or without lymphedema, and intellectual disability. The main manifestations of eye diseases are low vision, nystagmus, and chorioretinopathy. The heterozygous missense mutation c.895A>G (p.Ile299Val) in exon 8 of KIF11 gene is the pathogenic variant of this family.

Objective To explore the effects of dapnetin's regulation of STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats.Methods In this study,80 male Sprague Dawley(SD)rats were selected and randomly divided into four groups,20 rats in the sham-operation group,the remaining 60 mice with sepsis were constructed according to cecal ligation puncture(CLP)method and were intraperitoneally injected with different doses of dapnetin.They were divided into no-dapnetin model group(0 mg/kg),low-dose group(2.5 mg/kg),and high-dose group(5 mg/kg),with 20 mice in each group.The model group and sham-operation group were intraperitoneally injected with 0.1％DMSO.The survival rate of rats in each group after 72 h of CLP modeling was observed.Lung,kidney,liver and spleen tissues were collected for histopathological analysis.Serum inflammatory factors(TNF-α,IL-6,and IL-1β)were detected by ELISA,T lymphocyte subsets in peripheral blood were detected by flow cytometry,and STING/TBK1/IRF3 signaling pathway protein expression was detected by Western blotting.Results Compared with sham-operation group,the survival rate of rats in model group was reduced(P＜0.05),each organ tissue injury was significant,serum inflammatory factors(TNF-α,IL-6,and IL-1β)levels were increased(P＜0.05),CD4+ratio and CD4+/CD8+ratio in peripheral blood were decreased(P＜0.05),while CD8+ratio and Th1/Th2 ratio were increased(P＜0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were downregulated(P＜0.05).Compared with the model group,dapnetin in high-dose group improved the survival rate of rats(P＜0.05),the injury of all organs and tissues was reduced,and the level of serum inflammatory factors was decreased(P＜0.05),CD4+ratio and CD4+/CD8+ratio in peripheral blood were increased(P＜0.05),while CD8+ratio and Th1/Th2 ratio were decreased(P＜0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were increased(P＜0.05).Conclusion Dapnetin can improve the immune inflammatory response of sepsis rats by regulating STING/TBK1/IRF3 signaling pathway.