Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.
Female ; Male ; Humans ; Cross-Sectional Studies ; Sjogren's Syndrome ; Rheumatoid Factor ; Arthritis, Rheumatoid ; Blood Sedimentation ; Phenotype

PURPOSE: To evaluate the outcomes with and without aid of a computer-assisted surgical navigation system (CASNS) for treatment of unilateral orbital wall fracture (OWF). METHODS: Patients who came to our hospital for repairing unilateral traumatic OWF from 2014 to 2017 were included in this study. The patients were divided into the navigation group who accepted orbital wall reconstruction aided by CASNS and the conventional group. We evaluated the surgical precision in the navigation group by analyzing the difference between actual postoperative computed tomography data and preoperative virtual surgical plan through color order ratios. We also compared the duration of surgery, enophthalmos correction, restoration of orbital volumes, and improvement of clinical symptoms in both groups systemically. Quantitative data were presented as mean ± SD. Significance was determined by the two-sample t-test using SPSS Version 19.0 A p < 0.05 was considered statistically significant. RESULTS: Seventy patients with unilateral OWF were included in the study cohort. The mean difference between preoperative virtual planning and actual reconstruction outcome was (0.869 ± 0.472) mm, which means the reconstruction result could match the navigation planning accurately. The mean duration of surgery in the navigation group was shorter than it is in the control group, but not significantly. Discrepancies between the reconstructed and unaffected orbital-cavity volume and eyeball projection in the navigation group were significantly less than that in the conventional group. One patient had remnant diplopia and two patients had enophthalmos after surgery in the navigation group; two patients had postoperative diplopia and four patients had postoperative enophthalmos in the conventional group. CONCLUSION Compare with the conventional treatment for OWF, the use of CASNS can provide a significantly better surgical precision, greater improvements in orbital-cavity volume and eyeball projection, and better clinical results, without increasing the duration of surgery.

Ebola virus(EBOV) disease,the fatality rate of which is as high as 25％-90％,can be transmitted by contac t between human and non-human primates.Early studies of the virus focused on the functions of viral proteins.Recently,the focus of research of EBOV has been switched to the host interaction factors during the process of virus reproduction.In this review,advances in studies on host contributions to EBOV replication,transcription and translation are summarized in order to enhance our understanding of contributions of the host to the virus reproduction process and provide reference for research strategies and new antiviral drugs.

OBJECTIVETo investigate the effect of SAHA on the maturation of human dendritic cells (DC) and to explore its underlying mechanism.

METHODSPeripheral blood mononuclear cells (PBMNC) were isolated from human peripheral blood and cultured in RPMI 1640 medium with 100 ng/ml rhGM-CSF and 500 U/ml rhIL-4. In the LPS induced maturation process, dendritic cells treated with or without SAHA were used as test group, and dendritic cells treated without LPS or SAHA were used as control group. DC was observed under inverted microscope. Flow cytometer was used to detect the surface antigen molecules expressed by DC. The mixed lymphocyte culture (MLC) was used to observe the allogeneic lymphocyte stimulation. The NF-κB signaling pathway was detected by electrophoretic mobility shift assay (EMSA).

RESULTSThe SAHA could effectively suppress the maturation of DC induced by LPS, the DC treated with SAHA+LPS had immature morphological characteristics; the expression of CD80, CD83 and HLA-DR in SAHA+LPS group and control group were significantly down-regulated as compared with single LPS group (P<0.01); the ability of DC to stimulate the proliferation of allogeneic T lymphocytes in SAHA+LPS group and control group was significantly weaker than that in single LPS group (P<0.01); EMSA results showed that NF-κB activity decreased after SAHA and LPS treatment and was significantly lower than that of single LPS group.

CONCLUSIONSAHA can effectively suppress DC maturation induced by LPS and also weaken the ability to stimulate allogeneic T lymphocyte. NF-κB signaling pathway is involved in regulating DC maturation.

Cell Differentiation ; Dendritic Cells ; Flow Cytometry ; HLA-DR Antigens ; Humans ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; NF-kappa B ; T-Lymphocytes

Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 microM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over-expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.
Animals ; Animals, Newborn ; Blotting, Western/veterinary ; Caspase 3/*genetics/metabolism ; Cattle ; Cattle Diseases/etiology/*genetics/metabolism ; Duodenum/metabolism ; Enteritis/etiology/genetics/metabolism/*veterinary ; Epithelial Cells/metabolism ; *Gene Expression Regulation ; Glycoproteins/*genetics/metabolism ; Hydrogen Peroxide/pharmacology ; Male ; Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Real-Time Polymerase Chain Reaction/veterinary

This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH.
Achondroplasia ; genetics ; Cartilage Oligomeric Matrix Protein ; genetics ; Child, Preschool ; Cloning, Molecular ; Humans ; Male ; Mutation

OBJECTIVETo observe X-ray features of before and after treatment of cervical imbalance syndrome with osteopathy and traction intervention in youth patients, then to investigate the clinical effect of the treatment of the cervical imbalances syndrome in youth by osteopathy.

METHODSFrom September 2007 to December 2010, one hundred and eighty-seven students of 19 to 22 years (means 21 years) with neck pain as the main symptom in Beijing university of Chinese medicine were selected and divide them into osteopathy group and traction groups randomly. In osteopathy group, there were 94 patients including 40 males and 54 females; in traction group, there were 93 patients including 42 males and 51 females. The treatment of osteopathy group lasted for 3 weeks,three times per week; traction group by traction treatment three weeks,three times a week, too. X-ray before treatment and 3 weeks after treatment were collected.

RESULTSThe osteopathy group:94 cases, before treatment, abnormal curvature in 57 cases, spinous position change in 45 cases and angular displacement in 44 cases, vertebral sliding in 15 cases, Ruth Jackson line intersect proneness change in 70 cases,stretch change in 47 cases; after treatment, abnormal curvature in 35 cases, spinous position change in 24 cases and angular displacement in 18 cases, vertebral sliding in 3 cases, Ruth Jackson line intersect proneness change in 41 cases, extension change in 33 cases; X-Ray measurement results: cervical curvature improved from (7.070 +/- 4.629) degrees before treatment to (7.660 +/- 4.156) degrees after treatment, angular displacement improved from (13.790 +/- 2.590) degrees before treatment to (11.050 +/- 2.560) degrees after treatment; vertebral sliding improved from (3.770 +/- 0.350) mm before treatment to (3.160 +/- 0.485) mm after treatment. The change of angular displacement and vertebral sliding were so significant before and after treatment in this group, there were statistical defferences between before and after the treatment (P < 0.01) in osteopathy group. The traction group: 93 cases, before treatment,abnormal curvature in 60 cases, spinous position change in 39 cases and angular displacement in 39 cases, vertebral sliding in 15 cases, Ruth Jackson line intersect proneness change in 70 cases, stretch in 47 cases; after treatment,abnormal curvature in 50 cases, spinous position change in 29 cases and angular displacement in 17 cases; vertebral sliding in 3 cases, Ruth Jackson line intersect proneness change in 41 cases, stretch in 33 cases; X-Ray measurement results: cervical curvature improved from (5.590 +/- 4.639) degrees before treatment to (5.990 +/- 4.330) degrees after treatment, angular displacement improved from (13.360 +/- 2.064) degrees before treatment to (11.210 +/- 1.872) degrees after treatment; vertebral sliding improved from (3.790 +/- 0.339) mm before treatment to (3.480 +/- 0.332) mm after treatment. The change of angular displacement and vertebral sliding were also so significant in traction group before and after treatment, there were statistical defferences between before and after the treatment (P < 0.01).

CONCLUSION(1) Pathological changes can be called youth cervical imbalance syndrome. (2) Stress points, angular displacement, cervical vertebral slip, curvature straightened, spinous position change are main X-ray performances. (3) Both osteopathy and traction intervention on are efficient in youth neck pain. (4) Youths cervical vertebra imbalance is early but reversible performance.

Cervical Vertebrae ; diagnostic imaging ; Female ; Humans ; Joint Instability ; diagnostic imaging ; therapy ; Male ; Radiography ; Spinal Diseases ; diagnostic imaging ; therapy ; Traction ; X-Rays ; Young Adult