Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective:The objective of this study is to analyze the detection rate, the pathogenic fungus distribution, risk factors and drug sensitivity of fungal infection of external auditory canal in patients diagnosed with chronic otitis media. Methods:The data of a total of 419 patients with chronic suppurative otitis media or middle ear cholesteatoma who were admitted from January 2019 to February 2023 were retrospectively analyzed. Results:A total of 419 patients were included, and 71 patients（16.9%） were positive for fungal culture. The disease mostly occurred in subjects aged 51-60 years old, and patients over 60 years old（47 cases, 66.2%）. From the fungal culture of external auditory canal secretions, 48 cases（11.4%） of Aspergillus and 14 cases（3.3%） of Candida were identified. The prevalence of fungal cultures in patients with chronic suppurative otitis media（20.8%） was significantly higher than that in patients with middle ear cholectestoma（4.9%）. The detection rate of Fungal was significantly increased after topical treatment with antibiotic ear drops（47.0% vs 13.6%）. Most of the isolated fungal strains are wild-type, and they are the sensitivity to voriconazole and fluconazole was the highest（97.2%）. For patients with positive fungal culture, iodoform gauze with triamcinolone acetonide and econazole cream was used to fill the external auditory canal during surgery. There was no significant difference in the tympanic membrane healing rate between patients with positive fungal culture and patients with negative fungal culture at 3 weeks after surgery（98.6% vs 97.7%）. Conclusion:Fungal infections of external auditory canal in patients with chronic otitis media tend to occur in older patients, which is more common in patients with chronic suppurative otitis media. Long-term topical treatment with antibiotic ear drops is an independent risk factor for fungal infection of external auditory canal in patients with chronic otitis media. The isolated fungal strains were highly sensitive to antifungal drugs. Therefore, it is advisable to refrain from employing topical antibiotic treatment for elderly patients with chronic suppurative otitis media/middle ear cholesteatoma, abuse of local antibiotic therapy should be avoided, and Fungal-related pathogenic examinations should be actively performed and anti-fungal drugs should be added if necessary.
Humans ; Middle Aged ; Female ; Male ; Risk Factors ; Retrospective Studies ; Chronic Disease ; Otitis Media, Suppurative/microbiology* ; Ear Canal/microbiology* ; Antifungal Agents/therapeutic use* ; Adult ; Mycoses/epidemiology* ; Aspergillus/isolation & purification* ; Candida/isolation & purification* ; Otitis Media/complications* ; Aged ; Cholesteatoma, Middle Ear/microbiology*

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

The scientific interpretation of the theory of medicinal properties of TCM is a research hotspot in the modernization of TCM. It is of great value to clarify the property and degree of cold and heat in Chinese materia medica for guiding clinical precise medication. In recent years, the research on the cold and heat properties of Chinese materia medica has been carried out at the animal, cell and molecular levels. Based on the objective material basis of medicinal properties, from the perspective of biological effects such as thermodynamics and multiomics; with the help of infrared thermal imaging and other technologies for analysis; forming a variety of research models such as "property-structure relationship". Related research has developed from a single material component or index to a new model that tends to integrate multi-source information and multi-dimensional data. However, how to deal with the problems of large sample size, strong redundancy, high heterogeneity, and how to integrate multi-dimensional information are still research difficulties. With its powerful computing and learning ability, machine learning can show good discrimination and prediction ability in the study of cold and hot properties of Chinese materia medica, and play an important role in the study of cold and hot properties of Chinese materia medica. At present, the most widely used algorithms are linear discriminant analysis, Logistic discriminant analysis, support vector machine, decision tree, random forest and so on. The data dimension of the existing research needs to be enriched, the algorithm has room for further optimization, and a more detailed discriminant model of cold and hot properties of Chinese materia medica needs to be established.

Objective:To investigate the expression and clinical significance of gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1) in patients with gouty arthritis (GA).Methods:Differentially expressed genes (DEGs) between GA patients and healthy controls were identified by the Gene Expression Omnibus (GEO) database, followed by the screening of autophagy-related DEGs (au-DEGs) associated with GA. Peripheral blood single nucleated cells (PBMCs) were collected from 80 male GA patients and 60 healthy controls treated at the Affiliated Taizhou People′s Hospital of Nanjing Medical University between March to December 2023. Real-time quantitative PCR (qRT-PCR) was employed to assess the expression of au-DEGs, bisulfite sequencing PCR (BSP) was used to determine the methylation status of the GABARAPL1 promoter, and chromatin immunoprecipitation combined with qPCR (ChIP-qPCR) was used to analyze the binding activity of histone H3 to the GABARAPL1 promoter. Spearman ′s Correlations between GABARAPL1 expression and clinical indicators such as serum uric acid (UA) were analyzed. The diagnostic efficacy of GABARAPL1 in PBMCs for GA was evaluated using receiver operating characteristic (ROC) curves. Results:The relative expression of GABARAPL1 in PBMCs was significantly higher in GA patients compared to healthy controls (1.91±0.72 vs. 0.84±0.39, t=11.27, P<0.001). Spearman correlation analysis revealed that GABARAPL1 expression was positively correlated with UA, white blood cell count, neutrophil count, monocyte count, globulin, urea, and creatinine ( r=0.61, 0.40, 0.46, 0.32, 0.28, 0.22, 0.34; P<0.05 for all), and negatively correlated with lymphocyte count, albumin, high-density lipoprotein cholesterol, apolipoprotein A1, and estimated glomerular filtration rate ( r=-0.18, -0.34, -0.33, -0.50, -0.22; P<0.05 for all). ROC curve analysis showed that GABARAPL1 in PBMCs had high diagnostic efficacy for GA, with an area under the curve of 0.936. No significant differences in the methylation levels of GABARAPL1 promoter regions MC1 and MC2 were observed between GA patients and healthy controls ( t=2.28、1.43, P<0.05 for all), whereas histone H3 acetylation levels were significantly elevated in GA patients ( t=11.19, P<0.001). Conclusion:The expression of GABARAPL1 in PBMCs is significantly upregulated in GA patients, which may be associated with increased histone H3 acetylation at its promoter. The high expression of GABARAPL1 may contribute to the pathogenesis of GA by regulating autophagy and holds promise as a diagnostic biomarker and potential therapeutic target for GA.

OBJECTIVE To evaluate the status of microbial contamination in the environment of respiratory tract specimens sampling rooms and observe the association of the factors such as design and layouts of the sampling rooms with the potential risk of infections in the environment so as to provide scientific bases for optimizing the construction standards of fever clinics of the medical institutions.METHODS The sampling rooms of fever clinic were chosen from 10 tertiary or above medical institutions of Hangzhou,and the samples were collected from the key sites such as air,object surfaces and hands of health care workers.The respiratory tract pathogens in the sam-ples were detected by FilmArray full-automatic medical PCR analysis system,and the pathogens in the samples were detected by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry(MALDI-TOF MS).The data including the areas,windows,mechanical ventilation facilities,physical partitions,frequencies and modes of disinfection and daily amounts of diagnosis and treatment of the 10 sampling rooms were investigated,and the univariate analysis was performed for their association with the microbial contamination of environment.RESULTS The isolation rate of respiratory tract pathogens was 10.00％(4/40),respiratory syn-cytial virus,human rhinovirus and adenovirus were dominant among the respiratory tract pathogens.The isolation rate of bacteria was 71.88％(23/32),Staphylococcus ho minis and Staphylococcus epidermidis were the major species of opportunistic pathogens isolated.The result of univariate analysis indicated that both the presence of windows(P=0.012)and mechanical ventilation facilities(P=0.047)were associated with the potential risk of infections in the environment(P＜0.05);while the factors such as the areas of sampling rooms,physical parti-tions,disinfection modes and daily amounts of diagnosis and treatment were not remarkably associated with the potential risk of infections in the environment.CONCLUSION It is an effective way to physically separate the air-flow from other areas or fix the mechanical ventilation facilities to create proper airflow during the construction of fever clinic sampling rooms so as to reduce the potential risk of infections in the environment of sampling rooms.

Objective:To evaluate the efficacy and safety of endoscopic variceal ligation (EVL) of esophageal varices combined with endoscopic variceal intensive ligation (EVIL) of gastric varices for gastroesophageal variceal bleeding with liver cirrhosis under non-emergency settings.Methods:Data of 643 consecutive patients with gastroesophageal variceal bleeding due to liver cirrhosis admitted to the Department of Gastroenterology, Henan Provincial People's Hospital from January 2017 to March 2023 were included in the retrospective study. A total of 192 patients were included after excluding 451 patients. One hundred and forty-nine patients who underwent EVL of esophageal varices combined with EVIL of gastric varices were enrolled into the EVIL group, while 43 patients who underwent EVL of esophageal varices combined with endoscopic tissue adhesive injection (ETAI) of gastric varices were enrolled into the ETAI group. The endoscopic treatment success rate, esophageal variceal ligations number, operation time of endoscopic treatment, hospitalization time, rebleeding rate, mortality and the incidence of adverse events were compared between the two groups.Results:Compared with the ETAI group, the EVIL group exhibited significantly higher endoscopic treatment success rate [100.0% (149/149) VS 95.3% (41/43), P=0.049], slightly greater esophageal variceal ligations number [8 (6, 11) rings VS 7 (6, 9) rings, Z=-1.29, P=0.196], shorter operation time of endoscopic treatment [27.0 (20.5, 34.0) min VS 36.0 (21.0, 51.0) min, Z=-2.30, P=0.021], and significantly shorter hospitalization time [10 (7, 13) d VS 13 (9, 15) d, Z=-3.02, P=0.003]. The rebleeding rate within 24, 72, 120 hours after the operation, early, delayed and total rebleeding in the EVIL group were 0.0% (0/149), 0.0% (0/149), 0.7% (1/149), 2.0% (3/149), 12.8% (19/149) and 14.8% (22/149) respectively, and 4.7% (2/43) ( P=0.049), 9.3% (4/43) ( P=0.002), 9.3% (4/43) ( χ2=6.69, P=0.010), 4.7% (2/43) ( χ2=0.17, P=0.679), 30.2% (13/43) ( χ2=7.34, P=0.007) and 44.2% (19/43) ( χ2=17.20, P<0.001) in the ETAI group, respectively. No death related to rebleeding occurred within 6 weeks after the operation in 2 groups. The mortality related to rebleeding within 1 year after the operation and during the follow-up period in the EVIL group were 1.3% (2/149) and 3.4% (5/149) respectively, and 0.0% (0/43) ( P=1.000) and 2.3% (1/43) ( χ2=0.02, P=0.876) in the ETAI group, respectively. The incidences of fever, chest pain, nausea or vomiting in the EVIL group were 12.1% (18/149), 14.1% (21/149) and 13.4% (20/149) respectively, and 11.6% (5/43) ( χ2=0.01, P=0.936), 16.3% (7/43) ( χ2=0.13, P=0.721) and 18.6% (8/43) ( χ2=0.72, P=0.396) in the ETAI group, respectively. Two patients (1.3%) in the EVIL group had gastric variceal ring loss. Ectopic embolism occurred in 1 patient (2.3%) in the ETAI group. Conclusion:For patients with gastroesophageal variceal bleeding due to liver cirrhosis who are suitable for non-emergency endoscopic treatment, EVL of esophageal varices combined with EVIL of gastric varices is also safe, and more effective than EVL of esophageal varices combined with ETAI of gastric varices. This approach offers improved treatment success rate, reduced operation and hospitalization time, lower rebleeding rates, and decreased rebleeding-related mortality.

Objective To sort out the clinical research evidence on the promotion of wound healing after anal fistula surgery by traditional Chinese medicine in the past decade,and understand the evidence distribution in this field,the evidence map system was used.Methods Computer retrieval of CNKI,VIP,Wanfang,PubMed,Web of Science,EMbase,The Cochrane Library and other databases were searched.Interventional studies,observational studies,systematic review/meta-analysis on the treatment of postoperative anal fistula wounds by traditional Chinese medicine in the past decade were included.The evidence was analyzed and presented in the form of text and graphics.And the quality of clinical RCT was evaluated using Cochrane systematic review manual.AMSTAR was used to evaluate the quality of meta-analysis,and the JBI quality evaluation tool was used to evaluate the methodological quality of retrospective studies.Results A total of 544 articles were included.In recent 10 years,the number of published documents showed an increasing trend.The intervention measures of TCM to promote wound healing after anal fistula operation included single intervention mode and combined intervention mode.The outcome indexes mainly included clinical efficacy,basic wound condition,TCM syndrome score,adverse reactions,quality of life,long-term efficacy and so on.The overall quality of clinical RCT,retrospective analysis and systematic review/meta-analysis is low.Most studies showed that Chinese medicine had advantages in the treatment of vertigo,and more high-quality studies were still lacking.Conclusion More large-sample,multi-center RCTS should be carried out in the future,and the quality of relevant systematic review/meta-analysis should be improved.The advantages of TCM in promoting wound-heal after anal fistula surgery can be fully explored,which provide strong support for the effectiveness and safety of traditional Chinese medicine in improving wound management.