Objective To investigate the relationship between primary pulmonary mucinous adenocarcinoma (PPMA) mass type and pneumonia type and their difference in malignant degree, and to analyze the role of clinical manifestations and CT features in the diagnosis of this disease. Methods The clinical data of PPMA patients admitted in the First Affiliated Hospital of Xiamen University from May 2011 to March 2022 were retrospectively analyzed. According to CT features, they were divided into a mass type group and a pneumonia type group. The clinical manifestations, CT features and the degree of malignancy between the two groups were analyzed and compared. Results A total of 57 PPMA patients were enrolled. There were 17 males and 40 females, with an average age of (53.82±10.65) years, and 28 (49%) patients had reversed hato-like sign. There were 42 patients in the mass type group and 15 patients in the pneumonia type group. PPMA often occurs in both lower lungs, with clinical manifestations mainly of coughing and expectorating white mucoid sputum. There were statistical differences between the two groups in the maximum diameter of tumor (P<0.001), boundary condition (P<0.001) and pleural indentation sign (P=0.019). There was no statistical difference between the two groups in Ki-67 index (P>0.05). Conclusion There is no statistical difference in the degree of malignancy between the two types of PPMA. Considering their clinical manifestations and differences in imaging features, it is supported that the pneumonia type is just a progression of the mass type. CT can present various manifestations, among which the reversed hato-like sign is expected to become an important imaging feature. Combined with a high proportion of solid components, pleural indentation sign, and vacuole sign, reversed hato-like sign can play a significant role in the diagnosis of PPMA.

OBJECTIVE To analyze the peak wideband acoustic immittance(WAI)values reflecting the tympanic membrane absorption characteristics during the measurement process in patients with congenital middle ear malformation.METHODS We selected 36 patients diagnosed with congenital middle ear malformation by CT as subjects and evaluated their tympanic membrane absorption characteristics by measuring their acoustic impedance peak pressure.Then,we divided these data into two groups based on the pathological malformation obseved during the surgical process,namely the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group.Calculate the absorption rate values of the tympanic membrane at each frequency corresponding to the peak pressure value of the tympanogram,and the relative area of absorption rate.By conducting independent t-tests,we compared two groups-normal children and patients who had undergone ossicular chain fixation surgery-to analyze the absorption area and peak absorption rate of their tympanic peak pressure values.RESULTS Under peak pressure,there were significant differences(P<0.001)in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with fixed ossicular chain and the normal group.However,there was no difference in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with soft ossicular chain and the normal group.Under peak pressure,the absorption area of the ossicular chain fixation group was significantly lower than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001),while the absorption area of the ossicular chain soft connection group was significantly higher than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001).CONCLUSION When conducting broadband acoustic impedance test,there is a significant difference in the relative area of tympanic membrane absorption rate of acoustic impedance peak pressure between the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group across 226-1 000 Hz.It has application value as a clinical rapid screening and diagnostic tool for middle ear malformations.

Objective:A bidirectional Mendelian randomization approach was applied to dissect the causal association between dairy product consumption and osteoarthritis (OA), so to offering novel insights for the prevention, treatment, and prognosis assessment of knee osteoarthritis (KOA).Methods:A two-sample Mendelian randomization (MR) analysis was conducted using public available genome-wide association studies. The primary analysis was performed using the inverse variance weighted (IVW) method. To assess the stability and reliability of the results, we compared IVW and MR-Egger regression using Cochran′s Q test to evaluate SNP heterogeneity. MR-Egger regression was employed to assess pleiotropy, while a leave-one-out approach was used for sensitivity analysis. Results:Based on 207 instrumental variables (IVs), two-sample MR analysis revealed that for each standard deviation increase in genetically predicted cheese intake, the risk of OA was significantly negatively associated [ OR(95% CI)=0.98(0.98, 0.99), P<0.001], so did the risk of KOA [ OR(95% CI)=0.73(0.63, 0.85), P<0.001]. However, no significant association was found between OA risk and the intake of full-fat milk (30 IVs), semi-skimmed milk (15 IVs), skimmed milk (32 IVs), soy milk (25 IVs), or other types of milk (13 IVs), yogurt (11 IVs), or butter (3 IVs). Conclusion:The two-sample MR analysis revealed causally inverse associations between cheese intake and OA as well as KOA.

Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE-/-mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low-,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents decreased(P<0.05,P<0.01);the FINS and HDL-C content increased(P<0.05,P<0.01),intestinal acetic,propionic,butyric acid,isobutyric acid and isovaleric acid contents increased(P<0.05,P<0.01),GPR109A mRNA and protein expression in ileal tissue increased and NF-κB p65 mRNA and protein expression in ileal tissue decreased decreased(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Tongmai Prescription can improve glucolipid metabolism and inflammatory response in diabetic atherosclerotic mice,which may be related to regulating SCFAs/GPR109A pathway.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

OBJECTIVE: To determine the prevalence of GJB2 gene c.109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. METHODS: One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c.109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c.109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2023-009). RESULTS: For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c.109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c.109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined (n = 53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined (n = 24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls (P = 0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1 ± 12.0 dB nHL, P = 0.005). CONCLUSION Infants harboring the GJB2 c.109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c.109G>A variant can confer a more severe hearing loss.
Humans ; Connexin 26/genetics* ; Female ; Male ; Infant, Newborn ; Infant ; Hearing Loss/genetics* ; Retrospective Studies ; Child, Preschool ; Child ; Genotype ; Connexins/genetics* ; Mutation

Objective:To explore the clinical efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) based on the double difference (DID) model.Methods:A retrospective case - control study method was adopted to analyze the general data of 130 patients with trigeminal neuralgia (TN) who were treated in the Department of Neurosurgery of Hebei General Hospital from January 2022 to October 2023. Among them, 49 were males and 81 were females. The age was (53.28±11.67) years, ranging from 25 to 80 years old. According to different treatment methods, the patients were divided into an experimental group ( n=63) and a control group ( n=67). Patients in the experimental group were given percutaneous balloon compression (PBC) treatment, while those in the control group were treated with conservative drug therapy. Propensity score matching method was used for 1∶1 matching. After matching, there were 52 cases in each group. The general data of the two groups were compared. The visual analogue scale (VAS), 36-item short form health survey (SF-36) score, Hamilton depression rating scale (HAMD) score, Hamilton anxiety rating scale (HAMA) score, 5-hydroxytryptamine, neuropeptide P, inflammatory factor interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) before and after treatment, as well as the clinical efficacy of the two groups of patients were comparatively analyzed. Meanwhile, the incidence of postoperative complications in the two groups was compared. The generalized estimating equation (GEE) model was used to analyze the influencing factors of clinical efficacy, and the difference-in-differences (DID) model was used to evaluate the efficacy before and after treatment. Measurement data conforming to the normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; the chi- square test was used for comparison between count data. Results:After treatment, the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level in the experimental group were (2.98±0.83) points, (75.56±1.18) points, (7.2±0.83) points, (7.15±0.85) points, (76.34±5.47) ng/mL, (50.95±11.01) pg/mL, (29.45±7.08) ng/L, and (21.18±3.55) ng/L respectively. In the control group, there were (3.63±0.95) points, (73.23±1.13) points, (7.98±0.80) points, (8.04±0.84) points, (186.31±11.61) ng/mL, (86.52±13.32) pg/mL, (34.47±6.58) ng/L, and (26.36±5.80) ng/L, respectively. The differences between the two groups were statistically significant ( P<0.05).The cure rate and the total incidence of postoperative complications in the experimental group were 55.77% and 13.46% respectively, while in the control group, they were 40.38% and 30.77% respectively. The differences between the two groups were statistically significant ( P<0.05).The results of the GEE model analysis showed that age, course of disease, VAS, SF-36 score, HAMA score, HAMD score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, TNF-α level, treatment method, and the long - diameter ratio of FO significantly affected the clinical efficacy of patients ( P<0.05).The results of the DID model showed that the experimental group was superior to the control group in improving the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level( P<0.05). Conclusion:PBC can significantly improve the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine, neuropeptide P, IL-1, TNF-α, and incidence of complications in patients with TN. It can also improve the psychological status and quality of life of patients.

Objective:To investigate the effect and mechanism of Jiedu Xiaoying Patch in rats with Hashimoto's thyroiditis (HT).Methods:Totally 32 rats were randomly divided into a blank group of 8 rats and a model group of 24 rats. The HT rat model was prepared by freely drinking 0.064% sodium iodide solution in the modeling module. 24 successfully modeled rats were randomly divided into model group, selenium yeast group, and patch group, with 8 rats in each group. Starting from the 9th week, the application group applied Jiedu Xiaoying Patch to the surface projection area of the thyroid gland in the neck of rats for 6 hours, once a day, for a total of 6 weeks; the selenium yeast group was orally administered with 21 μg/ml selenium yeast solution at a dose of 0.5 ml/100 g, while the blank group, model group, and patch group were orally administered with equal volumes of physiological saline solution once a day for a total of 6 weeks. The levels of TGAb,TPOAb, Sema 5A, and IL-17A in rat serum were detected by ELISA. The changes of thyroid tissue was observed with HE staining. The relative expression levels of plexin-A1 and plexin-B3 were determined through RT-PCR.Results:Compared with the model group, the levels of TPOAb, TGAb, Sema 5A, and IL-17A decreased ( P<0.05), and the expressions of plexin-A1 and plexin-B3 decreased in the selenium yeast group and the patch group ( P<0.05). The thyroid follicles in the model group were severely damaged, with a large number of lymphocytes infiltrating the interstices; the thyroid follicular structure of the selenium yeast group was relatively intact, and lymphocyte infiltration was reduced compared to the model group. The thyroid follicular structure of the patch group was basically intact, with a small amount of lymphocyte infiltration observed. Conclusion:Jiedu Xiaoying Patch can significantly reduce the levels of TPOAb and TGAb in HT rats. The mechanism may be related to reducing the content of Sema 5A, inhibiting the expressions of receptors plexin-A1 and plexin-B3, reducing the production of inflammatory cytokines such as IL-17A, and inhibiting immune and inflammatory responses.