Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective To preliminarily compare ⁶LiF-⁷LiF and CR39 in individual neutron dose monitoring, and to provide a reference for improving individual neutron dose monitoring. Methods According to the GBZ 128-2019, 26 radiation workers from 7 institutions received individual neutron dose monitoring with ⁶LiF-⁷LiF and CR39 at the same time. The monitoring results were analyzed. Results For most of the workers, the personal neutron dose equivalent H_p(10) was less than the minimum detectable level. The results with the two monitoring methods differed in 6 of 26 workers. Conclusion Both ⁶LiF-⁷LiF and CR39 monitoring methods can be used for individual neutron dose monitoring for radiation workers, but the difference between ⁶LiF-⁷LiF and CR39 (in threshold energy, energy response, etc.) should be considered so that different types of radiation workers receive appropriate individual neutron dose monitoring.

Major depressive disorder （MDD） is an affective disorder characterized by significant and long-lasting depression， hypoactivity， and thinking and cognitive retardation. Some patients may conduct self-hram or suicide and have delusion， hallucination， and other mental symptoms. MDD is believed to be correlated with brain and heart， but there is no complete theory or mechanism fully explaining the pathogenesis of MDD. Traditional Chinese medicine （TCM） holds that the brain and heart dominate the formation of and change in mind， and MDD falls into the category of mental disease. It is mainly diagnosed as depression， visceral agitation， or Lily disease. Triple energizer is a key zang-fu organ that governs Qi transformation. There has always been some controversy about its anatomical structure. In recent years， important progress has been made in the research on the substantive structure of triple energizer. It is found that the structure and function of triple energizer are highly consistent to those of "mesenchyme"， a fluid space supported by a complex network of collagen fibers and widely distributed throughout the body. Different from known tissues and organs， it is a large organ responsible for information communication， material exchange， and energy metabolism. The triple energizer is partially contained in the structure of brain and heart and connects with the brain and heart， thus forming a "brain-heart-triple energizer" system with close physiological and pathological connections. With the association of "brain-heart-triple energizer" as the basis and Qi transformation as the core link， this paper elucidated the pathogenesis of MD and put forward that MDD resulted from "brain and heart Yang deficiency and Qi depression due to triple energizer obstruction"， so as to improve TCM understanding of the pathogenesis of MDD and perfect the TCM theories of encephalopathy and triple energizer.

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Child ; Humans ; COVID-19 ; SARS-CoV-2

Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15^th, 2022 to May 30^th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38⁺³±1⁺³) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30⁺¹ weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 10⁹ vs. 19.6 (15.4, 36.6) × 10⁹/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; COVID-19 ; Mothers ; Pregnancy Complications, Infectious/prevention & control* ; Retrospective Studies ; SARS-CoV-2

OBJECTIVE: To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients. METHODS: The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34 RESULTS: In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125). CONCLUSION The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.
Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Myelodysplastic Syndromes ; Platelet Transfusion ; Retrospective Studies

Spermatogenic dysfunction caused by cyclophosphamide (CP) chemotherapy has seriously influenced the life quality of patients. Unfortunately, treatments for CP-induced testicular spermatogenic dysfunction are limited, and the molecular mechanisms are not fully understood. For the first time, here, we explored the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) on CP-induced testicular spermatogenic dysfunction in vitro and in vivo. BMSC-exos could be taken up by spermatogonia (GC1-spg cells). CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses, and then, cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In addition, photophosphorylation of extracellular-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), and protein kinase B (AKT) proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry. Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells. Phosphorylated levels of ERK, AKT, and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos, indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. In experiments in vivo, CP-treated rats received BMSC-exos by injection into the tail vein, and testis morphology was compared between treated and control groups. Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes. Thus, BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

Osteoporosis （OP） is one of the most common diseases in the aged population worldwide. Due to the rapid change in world population structure， the effective prevention and treatment of OP is increasingly becoming the health problem of global concern and also the hot spot of clinical research. OP can be affected by many factors such as heredity， endocrine dyscrasia， nutritional deficiency， and bad living habits. The breakdown of coupling of osteoclast-mediated bone resorption to osteoblast-mediated bone formation leads to stronger bone resorption than bone formation， which is currently recognized as the main pathogenesis of OP. The exploration of OP in modern medicine based on molecular immunology has revealed that related cytokines play an important role in the pathogenesis of OP，and regulating the osteoclast-mediated bone resorption and osteoblast-mediated bone formation is essential for controlling the occurrence and development of OP. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） are able to stimulate bone formation and inhibit osteoblast function， thus playing a key role in bone destruction. By contrast， such cytokines as vascular endothelial growth factor （VEGF）， transforming growth factor-β （TGF-β）， bone morphogenetic protein （BMP）， and osteoprotegerin （OPG） strengthen osteoblast differentiation and promote bone formation. At present， western medicine like calcitonin， estrogen， and bisphosphonate are mostly used for clinical treatment of OP， but a long-term use of these drugs will result in poor compliance and obvious gastrointestinal adverse reactions. Traditional Chinese medicine （TCM） occupies an important position in the treatment of OP due to its advantages of overall regulation， low price， and few side effects. In addition， with the deepening of research on network pharmacology and molecular biology， it has been found that TCM exerts the therapeutic effect against OP by interfering with the expression of various cytokines and adjusting bone homeostasis. This paper has elaborated the role of related cytokines in the pathogenesis of OP and reviewed the research results concerning the regulation of related cytokines by TCM， in order to provide reference for the prevention and treatment of OP with TCM.