Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

BACKGROUND:Nobiletin has been found to improve lipopolysaccharide-induced abnormal activation of microglia,excessive release of inflammatory factors and redox imbalance.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the molecular mechanism by which nobiletin can inhibit lipopolysaccharide-induced inflammation in BV2 microglia. METHODS:Passage 3 BV2 microglia were divided into three groups:control group was cultured for 24 hours(without any treatment).Lipopolysaccharide group was treated with 10 μg/mL lipopolysaccharide for 24 hours.Lipopolysaccharide+nobiletin group was treated with 20 μmol/L nobiletin for 6 hours and then 10 μg/mL lipopolysaccharide for 24 hours.After the processing,cell proliferation was detected by CCK-8 assay.The level of intracellular reactive oxygen species was detected by fluorescent probe.The mRNA expression levels of nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β were detected by qRT-PCR.The protein expression levels of nuclear factor κB p65,p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β were detected by western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation activity of lipopolysaccharide group was decreased(P<0.001).Compared with the lipopolysaccharide group,the cell proliferation activity of lipopolysaccharide+nobiletin group was increased(P<0.001).(2)Compared with the control group,the level of intracellular reactive oxygen species was increased in the lipopolysaccharide group(P<0.001).Compared with the lipopolysaccharide group,the level of intracellular reactive oxygen species was decreased in the lipopolysaccharide+nobiletin group(P<0.01).(3)Compared with the control group,the mRNA expression levels of tumor necrosis factor α and interleukin-1β were increased in the lipopolysaccharide group(P<0.001,P<0.01).Compared with the lipopolysaccharide group,mRNA expression levels of tumor necrosis factor α and interleukin-1β were decreased in the lipopolysaccharide+nobiletin group(P<0.01,P<0.05).(4)Compared with the control group,the protein expression levels of p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β in were increased the lipopolysaccharide group(P<0.001).Compared with the lipopolysaccharide group,the expression of p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β was decreased in the lipopolysaccharide+nobiletin group(P<0.001).(5)These findings suggest that nobiletin attenuates lipopolysaccharide-induced inflammatory response in BV2 microglia by suppressing nuclear factor-κB signaling pathway.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics in two children with Knobloch syndrome (KNO) due to variants of COL18A1 gene. METHODS: Two children presented at the Genetic Eye Disease Clinic of the Eye Hospital of Wenzhou Medical University in October 2023 for ocular lesions were selected as the study subjects. Relevant clinical data and peripheral venous blood samples were collected from the children and their parents. Following genomic DNA extraction, whole-exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing of the family members. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-212-K-185). RESULTS: Both children exhibited characteristic ocular features of KNO including nystagmus, high myopia, and leopard spot fundus. Additionally, child 1 also presented with congenital occipital bone dysplasia and occipital encephalocele, while child 2 was diagnosed with vitreoretinochoroidopathy and bilateral high myopia. WES has identified compound heterozygous variants of the COL18A1 gene in both children, including a c.3013+3A>C splice-site variant and a c.2743C>T (p.Arg915Ter) nonsense variant in child 1, and a novel c.1702-1G>A splice-site variant and a c.3836C>T (p.Ser1279Leu) missense variant in child 2. A comprehensive literature review has identified 63 domestic and international articles involving 167 patients with KNO whom can be classified into three subtypes, with KNO type I being the most common and caused by pathogenic variants in the COL18A1 gene. Both probands in this study were children with KNO type I. Analysis of the genotype-phenotype correlations and population distribution characteristics revealed that the KNO patients exhibited significant clinical and genetic heterogeneity, along with a broad geographic distribution, with a relatively greater number of cases reported in Brazil and China. and a broad geographic distribution, with the highest numbers reported in Brazil and China. While no significant difference in genotype distribution was observed between Chinese and non-Chinese patients, phenotypic disparities were noted, with the non-Chinese cohort showing significantly higher rates of retinal detachment and developmental delay (P < 0.05), whereas Chinese patients exhibited a greater proportion of macular hypoplasia (P < 0.05). CONCLUSION The main clinical manifestations of KNO include high myopia, vitreoretinal dystrophy, and occipital encephalocele. The novel c.1702-1G>A splice-site variant identified in the COL18A1 gene has expanded the mutational spectrum of KNO type I and provided valuable insights for genetic diagnosis, counseling, and clinical management of the disease.
Humans ; Retinal Detachment/congenital* ; Male ; Female ; Child ; Encephalocele/genetics* ; Exome Sequencing ; Collagen Type XVIII/genetics* ; Phenotype ; Retinal Degeneration/genetics* ; Mutation ; Child, Preschool

Objective : To investigate the diagnostic value of plasma calprotectin in childern with refractory mycoplasma pneumoniae pneumonia(RMPP). Methods : A multicenter, prospective cohort study was conducted, enrolling 228 children with mycoplasma pneumoniae pneumonia(MPP). Among these, 177 cases were diagnosed with general mycoplasma pneumoniae pneumonia(GMPP), while the remaining 51 cases were RMPP. Plasma was collected at the time of admission of the children in both groups, and calprotectin levels were measured. A one-way difference analysis was performed on the blood test indexes of the children in the two groups, and the difference variables withP<0.05 between the two groups were included in a multifactorial logistic regression to analyze the risk factors for the progression of GMPP to RMPP. The differential diagnostic value of plasma calprotectin for GMPP and RMPP was analyzed by the receiver operating characteristic(ROC) curves. Results : Univariate analysis showed that plasma calprotectin levels were significantly higher in the RMPP group than those in the GMPP group, and the difference was statistically significant(P<0.05). Logistic regression analysis showed that plasma calprotectin was an independent risk factor for RMPP(OR=1.323,P<0.001), ROC curve analysis showed that plasma calprotectin had a higher diagnostic value for the differential diagnosis of GMPP and RMPP(AUC =0.839), and its combination with C-reactive protein and albumin could significantly improve the diagnostic efficiency. Conclusion Plasma calprotectin has good clinical value for the diagnosis of RMPP.

Objective:To summarize the clinical characteristics, treatment, and prognosis of children with anti-GT1a antibody-positive Guillain-Barré syndrome (GBS).Methods:A case series study was conducted, including 25 children diagnosed with serum anti-GT1a antibody-positive GBS at Guangzhou Women and Children′s Medical Center from March 2019 to December 2024. Clinical data, treatment protocols, and follow-up outcomes were analyzed. Mann Whitney U test was used to compare the changes in Hughes functional grading scale (HFGS). Results:A total of 25 children included 12 boys and 13 girls, and the age at first onset was (71±8) months. There were 16 children (64%) had preceding infections, and of which 13 children had predominantly respiratory tract infections. At disease peak, neurological manifestations included limb weakness (21 cases (84%)), bulbar palsy (13 cases (52%)), drowsiness (7 cases (28%)), limb pain (9 cases (36%)), ataxia (6 cases (24%)), respiratory muscle paralysis (5 cases (20%)), ophthalmoplegia (5 cases (20%)), and unilateral facial nerve palsy (4 cases (16%)). Cerebrospinal fluid analysis in 23 children revealed albuminocytological dissociation in 18 children. All 25 children underwent whole-spine magnetic resonance imaging (MRI), demonstrated spinal nerve root enhancement in 18 children, with leptomeningeal enhancement combined with spinal nerve root enhancement in 1 child. Electromyography in 16 children showed 15 children abnormality, of which demyelinating lesions in 8 children, mixed demyelinating-axonal changes in 4 children, and pure axonal involvement in 3 children. Intravenous immunoglobulin (IVIG) was administered to 21 cases (84%), of which 3 children required mechanical ventilation and blood purification (plasma exchange in 2 children and immunoadsorption in 1 child) due to disease progression. Four children (16%) received intravenous methylprednisolone (IVMP) instead of IVIG, with 1 child requiring ventilatory support due to respiratory muscle paralysis, and the tracheal tube was removed after continued sequential IVMP treatment. The hospitalization duration of 25 children was (23±3) d. At discharge, HFGS was 1.6 (0.6, 2.7) score. At a follow-up of 12 (4, 18) months, HFGS was 0.1 (0.0, 0.5) score, and higher than that at discharge ( Z=4.38, P<0.05). Two children relapsed but achieved remission after IVIG retreatment with no recurrence during 1-year follow-up. Conclusions:Anti-GT1a antibody-positive GBS in children predominantly presents with limb weakness and bulbar palsy, occasionally complicated by respiratory failure in the acute phase. Demyelinating neuropathy and spinal nerve root enhancement on MRI are characteristic. IVIG therapy yields favorable outcomes, with low residual disability. Relapses are rare but manageable with re-treatment.

Objective:To investigate the effect of osimertinib combined with pemetrexed and carboplatinon in patients with advanced lung adenocarcinoma epidermal growth factor receptor (EGFR) mutation, and its impact on serum interleukin-6 (IL-6) and cancer antigen 72-4 (CA72-4) levels.Methods:A total of 73 patients with advanced lung adenocarcinoma with EGFR mutation admitted to Peking University Medical Luzhong Hospital from December 2023 to December 2024 were prospectively selected and divided into a single group 36 cases and a treatment group 37 cases by random digits table method. The single group was treated with pemetrexed and carboplatin, and the treatment group was treated with osimertinib on the basis of the single group. The efficacy and pre- and post-therapy cellular immune function (CD 3+, CD 4+ and CD 4+/CD 8+), tumor markers [cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), CA72-4, tumor specific growth factor (TSGF), carcinoembryonic antigen (CEA)], vascular endothelial growth factor (VEGF), IL-6 and untoward reactions were compared. Results:Objective remission rate (ORR) and disease control rate (DCR) in the treatment group were greater than those in the single group: 27.03% (10/37) vs. 8.33% (3/36), 75.68% (28/37) vs. 52.78% (19/36), P<0.05. After therapy, CD 3+, CD 4+ and CD 4+/CD 8+ in the treatment group were higher than those in the single group: 0.675 ± 0.078 vs. 0.618 ± 0.067, 0.335 ± 0.033 vs. 0.275 ± 0.035, 1.25 ± 0.22 vs. 1.06 ± 0.15; the levels of TSGF, CEA, CYFRA21-1, CA72-4, IL-6 and VEGF in the treatment group were lower than those in the single group: (61.39 ± 7.43) kU/L vs. (78.23 ± 9.24) kU/L, (12.64 ± 1.42) μg/L vs. (16.87 ± 2.66) μg/L, (3.58 ± 0.48) μg/L vs. (4.14 ± 0.63) μg/L, (5.43 ± 0.81) kU/L vs. (7.06 ± 1.21) kU/L, (6.17 ± 0.82) ng/L vs. (8.57 ± 1.19) ng/L, (152.19 ± 18.14) pg/L vs. (216.47 ± 23.35) pg/L, P<0.05. The untoward reactions showed no statistical difference between two groups ( P>0.05). Conclusions:The joint of osimertinib combined with pemetrexed in the treatment of advanced lung adenocarcinoma patients with EGFR mutation is beneficial for improving efficacy, enhancing immune function, reducing tumor markers, and has certain safety.

Objective To explore the short and long term efficacy of ultrasound therapy combined with muscle imbalance adjustment training in patients with adhesive capsulitis(AC) ofthe shoulder. Methods A total of 60 AC patients were divided into an observation group and a control group,both each consisting of 30 cases. The observation group underwentultrasound therapy along with muscle imbalance adjustment training,while the control group received acupuncture treatment,both for a duration of 20 days. The Visual Analogue Scale(VAS),goniom-eter for ROM,Manual Muscle Testing(MMT),Constant-Murley Shoulder Score,and modified Barthel index were used to access shoulder jointpain level,range of motion (ROM),peripheral muscle strength,shoulder joint func-tion,and daily living abilities,respectively. The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were utilized to evaluate the levels of anxiety and depression.All the assessments were conducted and compared between the two groups before treatment,at the end of treatment,and at 6 and 12 months after treatment. Results Both groups showed varying degrees of improvement in ROM,MMT,VAS,Constant-Murley score,modified Barthel index,and emotional status compared to pre-treatment. The observation group demonstrated superior outcomes in posterior shoulder extension strength,VAS,Constant-Murley score,modified Barthel index,HAMA,and HAMD scores at the end of treatment (P<0.05). At 6 months post-treatment,the observation group showed better shoulder joint flexion,extension,abduction,and adduction ROM,as well as muscle strength in flexion,external rotation,and internal rotation,VAS,Constant-Murley score,modified Barthel index,HAMA,and HAMD scores. At 12 months after treatment,the observation group continued to show superior outcomes in all the aforementioned indexes (P<0.05). Conclusion The combination of ultrasound therapy and muscle imbalance adjustment training can effectively reduce shoulder joint pain,improve ROM,enhance muscle strength around the shoulder joint,improve shoulder joint function,alleviate anxiety and depression,and ultimately enhance the quality of life for patients with AC.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*