Objective On the basis of the theory of the tumor metastatic state, this work aims to explore the metastasis trajectories and peripheral immune response patterns in patients with non-small cell lung cancer (NSCLC) receiving vital qi-strengthening and toxin-eliminating therapy (Fuzheng Juandu) and reveal the value of peripheral immunity in assessing vital qi deficiency during metastasis. Methods A retrospective study design was adopted. Patients with NSCLC admitted from January 1, 2018, to October 31, 2025 were enrolled. Data on metastasis status and peripheral immune indices were collected at the follow-up time points of one, two, three, and five years. Group-based trajectory modeling was used to fit metastasis trajectories, and the independent predictors of trajectory grouping were analyzed through multifactor and multiclassification logistic regression. Results A total of 184 patients with NSCLC were included, and three different groups of metastasis trajectories were identified, namely, the low-risk stable (46.74%, n=86), low-risk rising (13.59%, n=25), and high-risk stable (39.67%, n=73) groups. Univariate analysis revealed substantial differences in peripheral immune indices among the three trajectory groups. Multivariate analysis showed that TNM stage, absolute neutrophil count, lymphocyte count, absolute monocyte count, platelet volume, SAA:CRP ratio, and NLR were independent predictors of the low-risk rising group, whereas TNM stage, absolute monocyte count, basophil count, SII, and NLR were independent predictors of the high-risk stable group. Conclusion Under Fuzheng Juandu therapy, patients with NSCLC exhibit three distinct metastasis trajectories, each corresponding to a specific peripheral immune response pattern. Elucidating these peripheral immune response patterns may facilitate the objective quantification of the degree of vital qi deficiency, prediction of future metastasis risk, and providing an important reference for the individualized clinical implementation of Fuzheng Juandu therapy.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

At present, acute brain injuries such as stroke and traumatic brain injury have become a serious burden on public health due to relatively limited treatment methods. As an emerging three-dimensional cell culture model, cerebral organoid can well redisplay the cellular diversity, tissue structure and functional characteristics of the human brain, providing an ideal platform for disease modeling, drug development and regenerative medicine research of acute brain injury. However, the construction and application of cerebral organoid are still in the exploratory stage at present, facing major technical bottlenecks such as insufficient vascularization, lack of immune microenvironment and tissue heterogeneity. This review summarizes the cultivation technique of cerebral organoid, highlights its application in acute brain injury, and analyzes its current technical bottleneck, so as to provide more reference basis for the development and application of this technology.

ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

OBJECTIVE: To evaluate the early effectiveness of transosseous suture fixation in treating recurrent acute patellar dislocation with patellar osteochondral fractures (OCFs). METHODS: A retrospective analysis was conducted on 19 patients with recurrent acute patellar dislocation and patellar OCFs, who underwent transosseous suture fixation between January 2018 and December 2022 and were followed up 2 years. The cohort included 8 males and 11 females, aged 13-21 years (mean, 16.2 years). Patients experienced 2-5 times of patellar dislocation (mean, 3.2 times). The interval from the last dislocation to operation ranged from 3 to 15 days (mean, 9.6 days). Preoperative imaging revealed the intra-articular osteochondral fragments and medial patellofemoral ligament (MPFL) injury. Clinical outcomes were evaluated using the visual analogue scale (VAS) score for pain, the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) knee score, the Lysholm score, and the Tegner score. Postoperative complications were recorded. During follow-up, the knee X-ray films, CT, and MRI were taken to evaluate fragment healing, displacement, and the morphology and tension of the MPFL reconstruction graft. RESULTS: All incisions healed primarily, and no complication occurred such as infection, joint stiffness, patellofemoral arthritis, or redislocation. Patients were followed up 24-60 months (mean, 43.5 months). At 12 months postoperatively and the last follow-up, significant improvements ( P<0.05) were observed in VAS, Lysholm, IKDC, HSS, and Tegner scores compared to preoperative values. Further improvements were observed at last follow-up compared with the 12 months postoperatively, and the differences were significant ( P<0.05). Imaging studies demonstrated satisfactory osteochondral fragment positioning with stable fixation. At last follow-up, all fragments had healed, and MPFL reconstruction grafts exhibited optimal morphology and tension. No joint adhesion or fragment displacement occurred. CONCLUSION For recurrent acute patellar dislocation with patellar OCFs, transosseous suture fixation proves to be both safe and effective, achieving satisfactory early effectiveness.
Humans ; Male ; Female ; Patellar Dislocation/surgery* ; Adolescent ; Young Adult ; Retrospective Studies ; Patella/surgery* ; Suture Techniques ; Treatment Outcome ; Recurrence ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Follow-Up Studies

OBJECTIVES: To investigate the causal associations between autoimmune diseases and aplastic anemia (AA) using Mendelian randomization analysis. METHODS: Publicly available genome-wide association study (GWAS) data were utilized to obtain single nucleotide polymorphisms (SNPs) associated with autoimmune diseases and AA for analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach, with MR Egger, Weighted Mode, Weighted Median, and Simple Mode methods serving as complementary analyses. Heterogeneity and pleiotropy analyses were conducted using designated functions, and the robustness of Mendelian randomization results was assessed using leave-one-out analysis. RESULTS: The two-sample Mendelian randomization analysis using the IVW method revealed significant positive causal associations of rheumatoid arthritis (OR=1.094, 95% CI: 1.023-1.170, P=0.009, adjusted P=0.042), systemic lupus erythematosus (OR=1.111, 95% CI: 1.021-1.208, P=0.015, adjusted P=0.036), Hashimoto thyroiditis (OR=1.206, 95% CI: 1.049-1.387, P=0.009, adjusted P=0.029), and Sicca syndrome (OR=1.173, 95% CI: 1.054-1.306, P=0.004, adjusted P=0.035) with AA, which was supported by the results from the Weighted Median method. Sensitivity analyses indicated no evidence of pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the causal relationships. No direct evidence was found linking Graves' disease, ulcerative colitis, Crohn's disease, autoimmune hepatitis, primary biliary cholangitis, or primary sclerosing cholangitis with AA (P>0.05, adjusted P>0.05), indicating a lack of causal association. Reverse Mendelian randomization results and multiple corrections indicated that AA was not an influencing factor for autoimmune diseases (adjusted P>0.05). CONCLUSIONS Our findings support at the genetic level that rheumatoid arthritis, systemic lupus erythematosus, Hashimoto thyroiditis, and Sicca syndrome are risk factors for AA, and confirm a causal association of the these 4 autoimmune diseases with an increased risk of AA.
Humans ; Mendelian Randomization Analysis ; Anemia, Aplastic/genetics* ; Autoimmune Diseases/complications* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Arthritis, Rheumatoid/genetics* ; Lupus Erythematosus, Systemic/genetics* ; Genetic Predisposition to Disease

Skeletal class Ⅱ malocclusion is characterized by maxillary protrusion,mandibular retrognathia,or a combination of both,and often accompanied by vertical dimensional discrepancies;treatment is complex,and combined orthodontic-orthognathic surgery is needed for the adult patients.Clear aligner therapy has gradually been applied in complex orthodontic cases.However,limited cases have been reported domestically and internationally regarding the application of clear aligner therapy combined with orthognathic surgery.This article presented a case of a patient with skeletal class Ⅱ high-angle malocclusion treated with the combined therapy and analyzed the clinical efficacy of the treatment appraoch to provide reference for the clinical practice.Extraction of impacted wisdom teeth 18,28,38,and 48,as well as orthodontic teeth 15,25,34,and 44,was performed in stages before orthodontic treatment.Clear aligner therapy was used for preoperative orthodontics.In sagittal plane,a super-complete class Ⅱ canine and molar relationship and a 13-14 mm overjet of the anterior teeth were established.The maxillary and mandibular arch morphology was matched horizontally.The orthognathic surgery included maxillary LeFort Ⅰ osteotomy,bilateral sagittal split ramus osteotomy(BSSRO)and chinplasty.Fine occlusal adjustment was conducted after operation.After treatment,the skeletal relationship between upper and lower jaw was corrected to normal;subspinale-nasion-supramental angle(ANB)was improved from 12.3° to 4.7°;the patient established the class Ⅰ canine and molar relationship,with normal overjet and overbite;root parallelism was good and there was no obvious root resorption;the facial soft tissue profile was significantly improved,and nasion-subnasale-pogonion angle(N-Sn-Pg)was improved from 143.9° to 162.8°.The curative effect was stable 1 year after operation.Clear aligner therapy can efficiently complete combined orthodontic and orthodontic surgery in the complex cases.Compared with the fixed appliance,it is more beneficial to the patients'need for beauty and the maintenance of periodontal health.

Objective:To clarify the changes in incidence and mortality of various cancers based on analysis on registration data of malignant tumor incidence and mortality from Dehui City and Yanji City in Jilin Province.Methods:The incidence and mortality data of malignant tumors from 2009 to 2016 in Dehui City and Yanji City in Jilin Province,were collected from the Chinese Cancer Registry Annual Report published by the National Cancer Center.The number of cases,deaths,crude incidence rate,crude mortality rate,age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and annual percentage change(APC)of the malignant tumors were analyzed by cancer sites and genders.Results:From 2009 to 2016,the CIR of malignant tumors in Dehui City(APC=1.2%,P=0.019)and Yanji City(APC=3.6%,P=0.058)showed an increasing trend.After standard population age adjustment,the ASIR in males in Dehui City showed a significant decline(APC=-5.7%,P=0.021),while the ASIR in females exhibited an overall downward trend,but the difference was not significant(APC=-2.2%,P=0.111).In Yanji City,the ASIR in males(APC=-1.4%,P=0.535)and females(APC=0.0%,P=0.988)showed no significant changes.The CMR of malignant tumors in Dehui City(APC=1.9%,P=0.001)and Yanji City(APC=5.9%,P=0.001)showed a continuous upward trend.After age-standardization,the ASMR in males(APC=-3.1%,P=0.100)and females(APC=-4.2%,P=0.053)in Dehui City,as well as in males(APC=-1.3%,P=0.438)in Yanji City,showed a slight downward trend.Although the ASMR in females in Yanji City showed a slight increase,the difference was not statistically significant(APC=0.5%,P=0.838).In 2016,the most common malignant tumor in terms of both incidence and mortality in Dehui City was lung cancer,with a CIR of 60.76/100 000 and a CMR of 46.96/100 000.In Yanji City,the most common malignant tumor was liver cancer,with a CIR of 49.04/100 000 and a CMR of 51.09/100 000.Conclusion:Lung cancer,liver cancer,and gastric cancer are the major malignant tumors threatening residents in Dehui City,Yanji City,and even the entire Jilin Province,and should be prioritized in cancer prevention and control efforts.Early diagnosis and treatment should be strengthened.

The patients with skeletal Class Ⅱ high-angle malocclusion are frequently complicated by idiopathic condylar resorption(ICR),which may lead to temporomandibular joint(TMJ)dysfunction and dentofacial deformities.This article reports the diagnosis and treatment process of a 24-year-old female patient with skeletal Class Ⅱ high-angle malocclusion accompanied by ICR.The patient's chief complaints were anterior open bite and TMJ pain,and was diagnosed with ICR through clinical examination and imaging.After stabilizing condylar resorption with occlusal splint therapy,combined orthodontic-orthognathic treatment was performed.The 42-month follow-up revealed:well-aligned dentition with complete closure of diastemas,significant improvement of protrusive facial profile(ANB angle reduced by 4.2°),complete resolution of TMJ pain and clicking,and establishment of stable Class Ⅰ occlusion.Three-dimensional CT demonstrated satisfactory condylar bone remodeling and normalized joint space.Through multidisciplinary treatment,both occlusal function and facial aesthetics were significantly improved.This case demonstrates that orthodontic-orthognathic treatment should be performed after condylar stabilization in ICR patients,and occlusal splint therapy serves as an effective preoperative intervention.

Objective:To explore the clinical characteristics and healthcare burden in patients with McCune-Albright syndrome (MAS).Methods:A cross-sectional study was conducted at the Children′s Hospital, Zhejiang University School of Medicine. Clinical and healthcare burden data were systematically collected through structured questionnaires in 164 children with MAS from February 2022 to May 2023. According to the clinical characteristics, patients were categorized into 3 groups: monosymptomatic, bisymptomatic and trisymptomatic groups. Patients were also divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Comparative analyses of clinical characteristics and healthcare burden were conducted across age, sex, and symptom categories.Results:The cohort comprised 59 males (36.0%) and 105 females (64.0%) with an age of 4.6 (2.0, 7.4) years. Age stratification revealed 117 cases (71.3%) aged 0-<7 years, 29 cases (17.7%) aged 7-<10 years, and 18 cases (11.0%) aged 10-<18 years. Among monosymptomatic (67 cases, 40.9%), the cohort comprised 32 females (47.8%) and 35 males (52.2%), predominantly presenting with fibrous dysplasia (57 cases, 85.1%). This subgroup showed peak prevalence in the 0-<7 years age range (29 cases (50.9%)). The bisymptomatic cohort (56 cases, 34.1%) consisted of 39 females (69.6%) and 17 males (30.4%), predominantly manifesting fibrous dysplasia with skin hyperpigmentation (25 cases, 44.6%). Peak prevalence occurred in the 0-<7 years subgroup(16 cases (64.0%)). The trisymptomatic cohort (41 cases, 25.0%) consisted of 34 females (82.9%) and 7 males (17.1%), with peak prevalence occurring in the 0-<7 years subgroup (36 cases (87.8%)). The diagnostic journey analysis revealed 94 cases (57.3%) required 1-3 referrals, and 34 cases (20.7%) necessitated >3 referrals from symptom onset to definitive diagnosis. Healthcare expenditure analysis revealed 69 families (42.1%) incurred direct medical costs of 10 000-100 000 CNY, with 11 families (6.7%) exceeding >100 000 CNY. Direct non-medical costs reached of 10 000-100 000 CNY for 62 families (37.8%) and >100 000 CNY for 4 families (2.4%). Productivity loss affected 58 families (35.4%) at 10 000-100 000 CNY and 8 families (4.9%) above 100 000 CNY during the study period.Conclusion:MAS requires increased attention to skeletal manifestations, especially in children aged 0-<7 years. Moreover, the significant financial burden on families necessitates a society-wide support system.