Objective:To explore the recurrence pattern and prognosis of cervical cancer after radical chemoradiotherapy.Methods:Clinical and follow-up data of 1 359 patients with stage Ⅰ-ⅣA (International Federation of Gynecology and Obstetrics 2009 staging) who received radical radiotherapy in Zhejiang Cancer Hospital from August 2011 to December 2017 were retrospectively analyzed. The survival and prognostic factors of 249 patients with recurrence / metastasis with detailed data were analyzed. The primary endpoint was post-recurrence / metastasis survival time. Kaplan-Meier method was used to calculate the survival rate, log-rank test was used for single factor analysis, and Cox model was used for multi-factor analysis.Results:The distant metastasis rate of 249 patients was 77.5%, and the local recurrence rate was 36.9%. According to the location of metastasis and recurrence, 56 cases with recurrence in the field of radiotherapy alone were assigned into group A, 157 cases with recurrence outside the radiation field alone were allocated into group B (56 cases with lymph node recurrence in group B1, 78 cases with blood metastasis in group B2, and 23 cases with lymph node and blood metastasis simultaneously in group B3), and 36 cases with combined recurrence and metastasis in and out of the field of radiotherapy were assigned into group C. The median survival time of patients in groups A, B1, B2, B3 and C was 13, 24, 13, 11 and 9 months, respectively (all P<0.001). According to the interval from initial diagnosis to recurrence / metastasis, 110 cases were classified in ≤1 year group, 74 cases in >1-2 years group, and 65 cases in >2 years group. The median survival time of patients in the three groups was 11, 14, and 22 months, respectively (all P<0.001). According to the management of recurrence / metastasis, 138 cases received palliative treatment, 15 cases received local treatment, 45 cases received systemic treatment, and 51 cases received combined treatment. The median survival time of patients among four groups was 9, 37, 20 and 32 months, respectively (all P<0.001). The results of multi-factor analysis showed that age, recurrence / metastatic site, retreatment methods, time interval between initial treatment and recurrence /metastasis were the independent prognostic factors affecting the survival (all P<0.05). Conclusions:Distant metastasis is the main failure pattern after radical radiotherapy. Patients with metastasis out of irradiated regions, especially those with only lymph node metastasis, have good prognosis. Active retreatment and time interval between initial diagnosis and recurrence / metastasis are important prognostic factors.

Objective:To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism(Ta-VTE),and to study the risk factors for Ta-VTE.Methods:The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled,and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor.The differences in clinical data and laboratory indicators between the two groups were analyzed,and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE.Results:A total of 288 patients with VTE were included in this study,including 64 cases in Ta-VTE group and 224 cases in pure VTE group,respectively.There were significant differences in the following indexes between the two groups,including the hospitalization time(14.20±15.29 d vs 10.05±6.90 d,t=3.112,P=0.002),pain(35.94％vs 65.18％,x2=17.554,P=0.000),recent surgery(75.00％vs 37.50％,X2=28.196,P=0.000),D-dimer[2.8(0.92,7.55)μg/ml vs 5.69(2.25,13.91)μg/ml,Z=-2.710,P=0.007],PLR[198.59(139.54,312.16)vs 149.76(114.08,233.66),Z=-2.924,P=0.003]and TBIL[10.90(7.63,15.68)μmol/Lvs 12.90(9.33,18.28)μmol/L,Z=-2.066,P=0.039].There was no significant difference in the other indicators(P＞0.05).The result of multivariate logistic regression analysis showed that elevated PLR(OR=1.003,95％CI:1.000-1.006,P=0.027),recent surgery(OR=4.312,95％CI:2.093-8.885,P=0.000)and prolonged hospitalization(OR=1.037,95％CI:1.002-1.074,P=0.038)were independent risk factors for Ta-VTE.However,pain(OR=0.274,95％CI:0.133-0.564,P=0.000)was a protective factor.Conclusion:Elevated PLR level,recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients,and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.

The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

Objective:To compare the difference of prognosis in ⅢCr stage cervical cancer patients with different T stage and lymph node status who received radical radiotherapy.Methods:Clinical data of 279 patients with ⅢCr stage cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. According to the latest American Joint Committee on Cancer (AJCC) TNM stage, all patients were divided into T 2a, T 2b, T 3a and T 3b stage groups, and N 1 and N 2 stage groups based on lymph node status. They were also divided into <1.85 cm and ≥1.85 cm groups according to the maximum short diameter of lymph node. In addition, they were assigned into ≤3 and>3 groups according to the number of lymph node metastasis. The differences of progression-free survival (PFS) and overall survival (OS) between patients with different T stage and lymph node status were compared by Kaplan-Meier test and log-rank test. Multivariate survival analysis was performed by Cox regression analysis. Results:Among 279 patients with ⅢCr stage cervical cancer receiving radical radiotherapy, 6 (2.2%) patients were diagnosed with stage T 2a stage, 109 (39.1%) patients with T 2b stage, 13 (4.7%) patients with T 3a stage, and 151 (54.1%) patients with T 3b stage. And 246 (88.2%) patients were diagnosed with N 1 stage and 33 (11.8%) patients with N 2 stage. According to the maximum short diameter of lymph nodes, there were 229 (82.1%) patients in the<1.85 cm group and 50 (17.9%) in the ≥1.85 cm group. According to the number of lymph node metastasis, there were 269 (96.4%) patients in the ≤3 group and 10 (3.6%) in the>3 group. There was no significant difference in the 5-year PFS ( P=0.136) and OS rates ( P=0.050) among patients with different T stages, and patients with T 3a stage had the worst prognosis (5-year OS rate was 38.5%). The 5-year PFS (48.0% vs. 64.2%, P=0.016) and OS rates (52.0% vs. 73.8%, P=0.001) in the ≥1.85 cm group were significantly lower than those in the<1.85 cm group. There was no significant difference in the 5-year PFS (61.0% vs. 63.6%, P=0.796) and OS rates (67.5% vs. 69.7%, P=0.770) between patients with N 1 and N 2 stages. There was no significant difference in the 5-year PFS (61.0% vs. 70.0%, P=0.653) and OS rates (67.3% vs. 80.0%, P=0.447) between patients in the number of metastatic lymph nodes ≤3 and>3 groups. The prognosis of patients with T 2b stage and the maximum short diameter ≥1.85 cm was the worst (5-year OS rate was 31.3%), while patients with T 2b stage and the maximum short diameter <1.85 cm obtained the best prognosis (5-year OS rate was 76.3%). Multivariate analysis showed that the maximum short diameter and radiation dose of lymph nodes were the independent relevant factors for the OS of ⅢCr stage cervical cancer patients (both P<0.05). Conclusions:Among ⅢCr stage cervical cancer patients receiving radical radiotherapy, clinical efficacy and prognosis significantly differ according to different T stage and lymph node status. Current staging system should be optimized to provide effective diagnostic and therapeutic regimens.

Objective To investigate the effects of the rhein on the mitochondria fission and epithelial-mesenchymal transition(EMT)of breast cancer cells MDA-MB-231.Methods Human breast cancer cells were intervened with rhein,and the cells were divided into control group(0 μmol·L-1),low dose rhein group(100 μmol·L-1),and high dose rhein group(200 μmol·L-1).The proliferation activity of the cells was detected by CCK-8,and migrations was detected by Scratch-healing migration assay.The morphology and distribution of mitochondria were detected by transmission electron microscope,and the expression levels of Dynamin-related protein 1(Drp1),mitofusin2(Mfn2),E-cadherin,Vimentin proteins were detected by Western blot.Results Compared with control group,Rhein significantly reduced the protein expression of Drp1、Vimentin(P<0.05),and increased E-cadherin and Mfn2,thus down-regulating mitochondria fission,inhibiting cell proliferation and migration.High dose Rhein was better than low dose.Conclusion Rhein can inhibit the proliferation and migration of breast cancer cells by reducing the expression of Drp1,Vimentin and up-regulating Mfn2,E-cadherin proteins.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To observe the effects of acupuncture at Houxi(SI3)and Huantiao(GB30)on the expression levels of nuclear factor kappa B(NF-κB),inducible nitric oxide synthase(iNOS),and nitric oxide(NO)of NF-κB inflammatory signaling pathway in L5 spinal nerve root of lumbar disc herniation(LDH)model rats and explore the mechanism of acupuncture in LDH treatment.Methods:Forty specific-pathogen-free healthy male Sprague-Dawley rats were randomly divided into a sham operation group,a model group,acupuncture group 1,and acupuncture group 2,with 10 rats in each group.The non-compression nucleus protrusion model was made by puncturing L4-L5 spinous process space and injecting autologous nucleus suspension.Acupuncture at bilateral Shenshu(BL23),Dachangshu(BL25),and Weizhong(BL40)was carried out in acupuncture group 1,and acupuncture at bilateral Houxi(SI3)and Huantiao(GB30)in acupuncture group 2.All rats were treated with balanced reinforcing and reducing needling manipulations,and the needles were retained for 30 min/time with one episode of needling manipulation every 10 min,once a day,14 times in total.The threshold value of paw withdrawal pain was measured by a thermal stimulation pain instrument;the serum NF-κB,iNOS,and NO levels were measured by enzyme-linked immunosorbent assay.The pathomorphological changes of spinal nerve roots were observed by hematoxylin-eosin(HE)staining;quantitative reverse transcription polymerase chain reaction was used to detect iNOS mRNA expression in spinal nerve roots;the NF-κB and iNOS protein expression in spinal nerve roots was detected by the immunofluorescence method.Results:Compared with the sham operation group,the threshold of paw withdrawal pain in the model group was decreased,and the expression levels of serum NF-κB,iNOS,and NO were increased;HE staining showed many degenerated and dissolved Schwann cells in spinal nerve roots with vacuolar changes;meanwhile,the expression levels of NF-κB and iNOS proteins,and the iNOS mRNA in spinal nerve roots were increased.Compared with the model group,the paw withdrawal pain thresholds in acupuncture group 1 and acupuncture group 2 were increased,and the increase in acupuncture group 2 was greater(P<0.05);the expression levels of serum NF-κB,iNOS,and NO in acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01);the vacuolar changes of spinal nerve roots,and the degeneration and lysis of Schwann cells in acupuncture group 1 and acupuncture group 2 were decreased,which were more obvious in acupuncture group 2;the NF-κB and iNOS protein expression and the iNOS mRNA expression levels in spinal nerve roots of acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01).Conclusion:Acupuncture at Houxi(SI3)and Huantiao(GB30)can improve the morphology of spinal nerve roots,inhibit the NF-κB and iNOS protein expression levels in spinal nerve roots and the serum NO level,and relieve the pain caused by inflammation of spinal nerve roots,which may be one of the mechanisms of acupuncture in LDH treatment.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Objective: To explore the effects of enteral immunonutrition support therapy on nutritional metabolism, immune function, and inflammatory response in adult burn patients at nutritional risk as assessed by the modified 2^nd nutrition risk screening (NRS) 2002. Methods: A prospective randomized controlled study was conducted. From December 2019 to January 2022, 500 adult patients who were admitted to the Affiliated Huaihai Hospital of Xuzhou Medical University and had nutritional risk assessed by the modified 2^nd NRS 2002 were recruited into the study. According to burn severity, the patients were divided into common burn patients (n=450) and severe burn patients (n=50). According to the random number table, the patients with common burn were divided into common burn diet nutrition group and common burn diet enteral immunonutrition group, with 225 patients in each group, and the patients with severe burn were divided into severe burn diet enteral non-immunonutrition group and severe burn diet enteral immunonutrition group, with 25 patients in each group. The patients in each group were given the corresponding nutritional support therapies on the basis of routine burn treatment. On post injury day (PID) 1, 3, 7, 14, and 21, the total energy intake and total protein intake of the patients in 4 groups were recorded, the plasma prealbumin, albumin, transferrin, serum immunoglobulin A (IgA), IgG, IgM, peripheral blood CD3 positive T cell percentage, CD4 positive T cell count, CD8 positive T cell count, the ratio of CD4 positive T cells to CD8 positive T cells, natural killer cell percentage, plasma interleukin-6 (IL-6), free mitochondrial DNA (mtDNA) copy number, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) of the patients in 4 groups were detected, and the nitrogen balance of the patients in 4 groups on the day was calculated. On PID 7, 14, and 21, the modified 2^nd NRS 2002 scores of the patients in 4 groups were reassessed. The sepsis incidence during treatment and the length of hospital stay of the patients in 4 groups and the length of intensive care unit (ICU) stay of the patients in the 2 severe burn groups were recorded. Data were statistically analyzed with chi-square test, Fisher's exact probability test, Mann-Whitney U test, independent sample t test, analysis of variance for repeated measurement, and Bonferroni correction. Results: A total of 476 patients completed the trial, with 213 patients in common burn diet nutrition group (112 males and 101 females, aged (37±19) years), 218 patients in common burn diet enteral immunonutrition group (115 males and 103 females, aged (42±16) years), 22 patients in severe burn diet enteral non-immunonutrition group (11 males and 11 females, aged (35±8) years), and 23 patients in severe burn diet enteral immunonutrition group (12 males and 11 females, aged (35±8) years). Compared with those in common burn diet nutrition group, the patients in common burn diet enteral immunonutrition group had significantly higher total energy intake on PID 1 (t=6.06, P<0.01), significantly lower total energy intake on PID 7 and significantly lower total protein intake on PID 1 (with t values of 6.17 and 4.59, respectively,P<0.01). On PID 21, the total energy intake of patients in severe burn diet enteral immunonutrition group was significantly lower than that in severe burn diet enteral non-immunonutrition group (t=2.70, P<0.01). The total protein intake of patients in severe burn diet enteral immunonutrition group and severe burn diet enteral non-immunonutrition group were similar at each time point post injury (P>0.05). Compared with those in common burn diet nutrition group, the patients in common burn diet enteral immunonutrition group had significantly higher level of prealbumin on PID 3, 7, 14, and 21 (with t values of 2.05, 2.33, 2.45, and 2.11, respectively, P<0.05), significantly higher level of albumin on PID 7, 14, and 21 (with t values of 2.30, 2.56, and 2.15, respectively, P<0.05), significantly higher level of transferrin on PID 7 and 14 (with t values of 1.99 and 2.27, respectively, P<0.05), significantly higher nitrogen balance on PID 14 and 21 (with t values of 2.51 and 2.07, respectively, P<0.05), and significantly lower modified 2^nd NRS 2002 score on PID 21 (t=1.99, P<0.05). Compared with those in severe burn diet enteral non-immunonutrition group, the patients in severe burn diet enteral immunonutrition group had significantly higher level of prealbumin on PID 3, 7, 14, and 21 (with t values of 2.50, 2.64, 2.18, and 2.39, respectively, P<0.05), significantly higher level of albumin​on PID 7, 14, and 21 (with t values of 2.27, 2.39, and 2.69, respectively, P<0.05), significantly higher level of transferrin and nitrogen balance but significantly lower modified 2^nd NRS 2002 score on PID 14 and 21 (with t values of 2.30, 2.35, 2.41, 2.16, 2.31, and 2.73, respectively, P<0.05). Compared with those in common burn diet nutrition group, patients in common burn diet enteral immunonutrition group had significantly higher level of IgA and IgG on PID 7, 14, and 21 (with t values of 2.19, 2.36, 2.17, 2.49, 1.97, and 2.24, respectively, P<0.05), significantly higher level of IgM on PID 21 (t=2.06, P<0.05), significantly higher percentage of CD3 positive T cells and ratio of CD4 positive T cells to CD8 positive T cells on PID 3, 7, 14, and 21 (with t values of 2.49, 2.25, 2.33, 2.41, 2.39, 2.24, 2.46, and 2.18, respectively, P<0.05), significantly higher CD4 positive T cell count (with t values of 2.15 and 2.27, respectively, P<0.05) but significantly lower CD8 positive T cell count on PID 14 and 21 (with t values of 2.58 and 2.35, P<0.05), and significantly higher percentage of natural killer cells on PID 7, 14, and 21 (with t values of 2.53, 2.21, and 2.36, respectively, P<0.05). Compared with those in severe burn diet enteral non-immunonutrition group, patients in severe burn diet immunonutrition group had significantly higher level of IgA on PID 7 and 14 (with t values of 2.15 and 2.03, respectively, P<0.05), significantly higher level of IgG on PID 7, 14, and 21 (with t values of 2.09, 2.56, and 2.15, respectively, P<0.05), significantly higher level of IgM on PID 21 (t=2.08, P<0.05), significantly higher percentage of CD3 positive T cells, CD4 positive T cell count, and percentage of natural killer cells on PID 14 and 21 (with t values of 2.52, 2.14, 2.14, 2.39, 2.56, and 2.19, respectively, P<0.05), significantly lower CD8 positive T cell count but significantly higher ratio of CD4 positive T cells to CD8 positive T cells on PID 7, 14, and 21 (with t values of 2.27, 2.81, 2.01, 2.11, 2.69, and 2.05, respectively, P<0.05). Compared with those in common burn diet nutrition group, patients in common burn diet enteral immunonutrition group had significantly lower level of IL-6 (with t values of 2.34 and 2.32, respectively, P<0.05) and significantly lower free mtDNA copy number on PID 14 and 21 (with Z values of -2.28 and -2.34,respectively, P<0.05), significantly lower level of sTREM-1 on PID 7, 14, and 21 (with t values of 2.02, 2.94, and 3.72, respectively, P<0.05). Compared with those in severe burn diet enteral non-immunonutrition group, patients in severe burn diet enteral immunonutrition group had significantly lower level of IL-6 and sTREM-1 on PID 7, 14, and 21 (with t values of 2.15, 2.29, 2.47, 2.43, 2.07, and 2.32, respectively, P<0.05), and significantly lower free mtDNA copy number on PID 14 and 21 (with Z values of -2.49 and -2.21, respectively, P<0.05). During treatment, the sepsis incidences of patients in 2 common burn groups were similar (P>0.05), the sepsis incidences of patients in 2 severe burn groups were similar (P>0.05). The length of ICU stay of patients in severe burn diet enteral immunonutrition group was (11±3) d, which was significantly shorter than (14±3) d in severe burn diet enteral non-immunonutrition group (t=3.12, P<0.01). The length of hospital stay of patients in common burn diet enteral immunonutrition group was significantly shorter than that in common burn diet nutrition group (t=3.11, P<0.01). The length of hospital stay of patients in severe burn diet enteral non-immunonutrition group was similar to that in severe burn diet enteral immunonutrition group (P>0.05). Conclusions: Enteral immunonutrition support therapy for adult burn patients at nutritional risk assessed by the modified 2^nd NRS 2002 can better improve the nutritional status and the immune function of patients, reduce inflammatory response of the body, and shorten the length of hospital stay in common burn patients and the length of ICU stay in severe burn patients.
Adult ; Burns/therapy* ; DNA, Mitochondrial ; Enteral Nutrition ; Female ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Interleukin-6 ; Male ; Middle Aged ; Nitrogen ; Prealbumin ; Prospective Studies ; Sepsis ; Transferrins