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.

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Objective:Using surface-based morphometry (SBM), this study longitudinally tracks dynamic changes in whole-brain cortical morphological parameters in depression patients before and after vortioxetine treatment. Through three-dimensional topological characterization, we investigate the neuroanatomical correlations between cortical structural reorganization and improvements in affective symptoms and cognitive functions.Methods:Prospectively collected clinical data from 22 outpatients with depression (10 males and 12 females, aged 18-50 years, mean age 28.1±9.1) who attended Beijing Huilongguan Hospital clinic from October 2018 to December 2019. An age-matched healthy control group ( n=21; 10 males and 11 females, aged 22-44 years, mean age 30.8±6.6) was recruited concurrently. The Hamilton Rating Scale for Anxiety (HAMA), the 17-item Hamilton Depression Scale (HAMD 17), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the severity of depressive symptoms and cognitive function in patients. Structural magnetic resonance imaging (sMRI) was performed to assess brain structural indices in depression patients before and after vortioxetine treatment, as well as in healthy controls. Whole-brain cortical structure measurements were calculated for all subjects using CAT12 software. Paired-sample t-tests were used to compare changes in cortical structure and clinical scale scores in depression patients before and after treatment, and two-sample t-tests were conducted to compare whole-brain cortical structure differences between patients (pre-and post-treatment) and healthy controls. Multiple regression analysis in SPM 12 was applied to examine the correlation between post-treatment cortical structural indices and clinical and cognitive scale scores in patients. Spearman correlation analysis was used to evaluate the correlation between changes in whole-brain cortical structure and cognitive function before and after vortioxetine treatment. Results:After vortioxetine treatment, patients with depression exhibited significant reductions in HAMA and HAMD 17 scores, along with significant increases in immediate memory, delayed memory, and total RBANS scores, with statistically significant differences observed ( t=8.43, 12.28, -4.71, -2.41, -3.86 respectively; all P<0.05), while there were no significant changes in visual span, language function, or attention ( P>0.05). Compared to healthy controls, depression patients showed a significantly reduced gyrification index in the right insula/superior temporal gyrus before treatment (28.74±1.20 vs 27.44±1.17; t=4.47, P<0.001), but no significant differences in whole-brain cortical structure were observed before and after treatment or between post-treatment patients and healthy controls ( P>0.05). Correlation analysis indicated that fractal dimension was negatively correlated with HAMA and HAMD 17 scores after treatment, while gyrification index was positively correlated with HAMD 17 ( rpartial=-0.79, -0.83, 0.72; P<0.05). Visual span was positively correlated with fractal dimension ( rpartial=0.78) and negatively correlated with gyrification index ( rpartial=-0.73, P<0.05). Sulcal depth was negatively correlated with attention and RBANS total scores ( rpartial=-0.77, -0.75; P<0.05). Additionally, changes in gyrification index in the left fusiform gyrus were positively correlated with changes in attention ( r=0.51), changes in gyrification index in the left posterior cingulate gyrus were positively correlated with changes in immediate memory ( r=0.58), and changes in sulcal depth in the left superior frontal gyrus were negatively correlated with changes in language ability ( r=-0.79) (both P<0.05). Conclusion:Vortioxetine treatment can improve anxiety and depressive symptoms in depression patients, as well as enhance certain cognitive functions, while also affecting cortical structure in the specific cortical area. Changes in cortical structure after vortioxetine treatment are closely related to clinical symptom improvement and cognitive function changes.

Objective To compare the macular retinal thickness characteristics of diabetic kidney disease(DKD)patients with different blood pressure levels and explore the relationship between blood pressure and macular retinal damage in DKD patients.Methods A total of 435 DKD patients were selected and divided into four groups based on medical history and blood pressure:the non-hypertensive group(NH group,n=100),the well-controlled blood pressure group(G0 group,n=176),the grade 1 hypertension group(G1 group,n=118)and the grade 2 hypertension group(G2 group,n=41).General information,routine laboratory test results as well as the average thickness of the macular retinal nerve fiber layer(RNFL),ganglion cell layer(GCL),ganglion cell complex(GCC),choroidal layer(CL)and central macular retinal thickness(CMT)were compared between the four groups.The correlation between macular retinal thickness in both eyes and clinical data was analyzed.Results Compared with the G1 group and the G2 group,the G0 group had a longer duration of hypertension.Compared to the NH group,the G2 group had higher fasting plasma glucose(FPG).Compared to the G0 group,the G1 group and the G2 group had higher FPG,and the G2 group had higher glycated hemoglobin(HbA1c)and lower estimated glomerular filtration rate(eGFR).Compared to the NH group,the G0 group had decreased thickness in the GCL and GCC(P<0.05).The macular retinal thickness of the GCL and GCC in both eyes was negatively correlated with diastolic blood pressure(r=-0.158 and-0.195,respectively,P<0.05).Conclusion Macular retinal thickness is helpful in assessing the long-term effects of hypertension on optic nerve and microvascular damage in DKD patients.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

OBJECTIVE To analyze the situation of urinary tract infections(UTIs)in children of different age groups in a health care hospital of Guangxi,and to analyze the detected pathogens and drug resistance rate.METHOD Data on urinary tract infections in children between 2017 and 2023 in Guangxi provincial maternal and child healthcare hospitals were retrospectively analyzed,and children were classified according to age:neonates(≤28 days),infants(＞28 days and ≤1 year),preschoolers(＞1 year and＜6 year)and 6-14 years old.The urina-ry tract infections,pathogen identification and drug resistance rates of major pathogens in children of different age groups were analyzed.RESULTS The pathogens of pediatric UTIs in each group were dominated by gram-negative bacilli(44.16％-67.36％),with the highest percentage of Escherichia coli(21.81％—38.60％),gram-posi-tive infections were dominated by Enterococcus faecium(5.96％—21.40％)and Enterococcus faecalis(4.66％—13.68％),and fungi were dominated by Candida albicans(8.03％-12.75％).Admission to intensive care unit was higher in the neonates group(37.38％,P＜0.001).Urine culture positivity rate was elevated in the 6-14 years age group(31.93％,P＜0.001),with girls being more common(59.47％,P＜0.001).The rate of E.coli resistance to cephalosporins was relative high in urine culture isolates from the infant group(28％—54％).In ad-dition,the resistance rate of Enterococcus faecium from urine to ampicillin was higher in the infant group than that in the preschool children and 6-14 years old groups(P=0.002).CONCLUSIONS The gram-negative bacteri-a were dominant among the pathogens isolated from the children with urinary tract infections and showed certain drug resistance to the commonly used antibiotics.Urinary tract infections are more difficult to diagnose and treat in younger children,and pediatricians should pay more attention to them.

Objective To compare the macular retinal thickness characteristics of diabetic kidney disease(DKD)patients with different blood pressure levels and explore the relationship between blood pressure and macular retinal damage in DKD patients.Methods A total of 435 DKD patients were selected and divided into four groups based on medical history and blood pressure:the non-hypertensive group(NH group,n=100),the well-controlled blood pressure group(G0 group,n=176),the grade 1 hypertension group(G1 group,n=118)and the grade 2 hypertension group(G2 group,n=41).General information,routine laboratory test results as well as the average thickness of the macular retinal nerve fiber layer(RNFL),ganglion cell layer(GCL),ganglion cell complex(GCC),choroidal layer(CL)and central macular retinal thickness(CMT)were compared between the four groups.The correlation between macular retinal thickness in both eyes and clinical data was analyzed.Results Compared with the G1 group and the G2 group,the G0 group had a longer duration of hypertension.Compared to the NH group,the G2 group had higher fasting plasma glucose(FPG).Compared to the G0 group,the G1 group and the G2 group had higher FPG,and the G2 group had higher glycated hemoglobin(HbA1c)and lower estimated glomerular filtration rate(eGFR).Compared to the NH group,the G0 group had decreased thickness in the GCL and GCC(P<0.05).The macular retinal thickness of the GCL and GCC in both eyes was negatively correlated with diastolic blood pressure(r=-0.158 and-0.195,respectively,P<0.05).Conclusion Macular retinal thickness is helpful in assessing the long-term effects of hypertension on optic nerve and microvascular damage in DKD patients.

OBJECTIVE To analyze the situation of urinary tract infections(UTIs)in children of different age groups in a health care hospital of Guangxi,and to analyze the detected pathogens and drug resistance rate.METHOD Data on urinary tract infections in children between 2017 and 2023 in Guangxi provincial maternal and child healthcare hospitals were retrospectively analyzed,and children were classified according to age:neonates(≤28 days),infants(＞28 days and ≤1 year),preschoolers(＞1 year and＜6 year)and 6-14 years old.The urina-ry tract infections,pathogen identification and drug resistance rates of major pathogens in children of different age groups were analyzed.RESULTS The pathogens of pediatric UTIs in each group were dominated by gram-negative bacilli(44.16％-67.36％),with the highest percentage of Escherichia coli(21.81％—38.60％),gram-posi-tive infections were dominated by Enterococcus faecium(5.96％—21.40％)and Enterococcus faecalis(4.66％—13.68％),and fungi were dominated by Candida albicans(8.03％-12.75％).Admission to intensive care unit was higher in the neonates group(37.38％,P＜0.001).Urine culture positivity rate was elevated in the 6-14 years age group(31.93％,P＜0.001),with girls being more common(59.47％,P＜0.001).The rate of E.coli resistance to cephalosporins was relative high in urine culture isolates from the infant group(28％—54％).In ad-dition,the resistance rate of Enterococcus faecium from urine to ampicillin was higher in the infant group than that in the preschool children and 6-14 years old groups(P=0.002).CONCLUSIONS The gram-negative bacteri-a were dominant among the pathogens isolated from the children with urinary tract infections and showed certain drug resistance to the commonly used antibiotics.Urinary tract infections are more difficult to diagnose and treat in younger children,and pediatricians should pay more attention to them.