Humans ; Pleura/pathology* ; Solitary Fibrous Tumor, Pleural/pathology* ; Adenocarcinoma of Lung ; Lung Neoplasms ; Pleural Neoplasms/pathology*

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Objective: To assess the efficacy of a bioabsorbable steroid-eluting sinus stent in improving surgical outcomes when placed in the frontal sinus ostium (FSO) following full endoscopic sinus surgery (ESS) in patients with whole group chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients with whole group CRSwNP who had similar lesions on bilateral sinus between September 2019 and March 2020 in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changhai Hospital were chosen. Patients with CRSwNP who underwent extended ESS were randomly assigned to receive a steroid-eluting sinus stent in one FSO whereas the contralateral side received surgery alone. Endoscopic evaluations recorded at 30, 90 days postoperative were graded by an independent assessment panel to assess the need for interventions in the FSO. Semi-quantitative data with CT and endoscopic score were performed by rank sum test. The need for postoperative intervention and the patency rate of FSO were analyzed using the McNemar test. Results: Thirty-one patients with whole group CRSwNP met all eligible criteria, including 17 males and 14 females, with the age of (44.5±11.8) years(x¯±s). Stents were successfully placed in one FSO of all patients. At 30 days post-ESS, the assessment panel reported that steroid-eluting stents reduced the need for postoperative interventions by 41.0% (χ²=5.314,P=0.021), the need for oral steroid interventions by 40.0% (χ²=4.133,P=0.042) and the need for surgical interventions by 74.8% (χ²=4.292,P=0.038) compared to control sinuses with no stents. Clinical surgeons also reported greater diameter of FSO compared to control sinuses at 30 days post-ESS (74.2% vs 48.4%, χ²=4.351, P=0.037). These results at 90 days post-ESS were consistent with those at 30 days post-ESS. Conclusion: Bioabsorbable steroid-eluting sinus stents in the FSO can reduce polyp formation, adhesion, and the need for postoperative interventions in FSO of CRSwNP patients and improve the early postoperative outcomes.
Absorbable Implants ; Adult ; China ; Chronic Disease ; Endoscopy ; Female ; Frontal Sinus/surgery* ; Humans ; Male ; Middle Aged ; Nasal Polyps/complications* ; Paranasal Sinuses ; Rhinitis/complications* ; Stents ; Steroids ; Treatment Outcome

Lung cancer， a malignancy with high incidence rate and mortality rate， is a major threat to human life and health. At present， the common methods for the treatment of lung cancer include surgical resection， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， but these methods generally have the problems of severe toxic/side effect and high treatment cost. Traditional Chinese medicine（TCM） has a history of more than 2 000 years of application in China and has its unique advantages in the treatment of tumors. Modern pharmacological experiments have found that TCM can inhibit tumor growth， prolong patients' survival， and improve clinical symptoms and patients' quality of life by inducing tumor cell apoptosis， inhibiting tumor angiogenesis， and reducing tumor cell drug resistance. Apoptosis is a process of spontaneous programmed cell death， which is closely related to the occurrence and development of the tumor. Studies have shown that many Chinese medicines can inhibit the development of lung cancer by inducing apoptosis. This study searched， analyzed， and summarized the available papers on the mechanism of TCM in the treatment of lung cancer by inducing apoptosis. It is found that Chinese medicine induces lung cancer cell apoptosis mainly by regulating apoptosis-related factors and apoptosis-related signaling pathways ［inhibitor of apoptosis proteins （IAPs）， B cell lymphoma-2 （Bcl-2）， p53 protein， the second mitochondria-derived activator of caspase （SMAC）/direct IAP-binding protein with low isoelectric point （DIABLO）， extrinsic apoptotic pathway， endogenous mitochondrial pathway， Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. In addition， the Wnt/β-catenin/survivin signaling pathway and the Notch signaling pathway also play an important role in inducing apoptosis.

OBJECTIVE: To explore the curative effects of the combined therapy of laparoscopic partial sigmoidectomy and anterior and posterior vaginal wall repair for the treatment of severe pelvic floor dysfunction(PFD).METHODS: The clinical data of 14 severe PDF patients(uterine prolapse in stage Ⅲ-Ⅳ）with dolichasigmoid were studied retrospectively from May 2017 to August 2018 in Shanghai Traditional Chinese Medical University. The surgical way was laparoscopic partial sigmoidectomy and anterior and posterior vaginal wall repair. The objective effects were assessed by comparing the position of each indication points of the preoperative and postoperative pelvic organs' prolapse(in POP-Q scale).Subjective effects were also assessed by comparing Clevel score of constipation,pelvic floor distress inventory-short form 20(PFDI-20),pelvic floor impact questionnaire short form(PFIQ-7)between preoperation and 6 months and 1 year after operation.RESULTS: All 14 patients were successfully operated on without any intra-operative and post-operative complications. The comparion of positions of the POP-Q indication points(AA,Ba,C,D,AP,BP)between preoperation and 1 year after operation showed the difference was statistically significant(P<0.01). PFDI-20,PFIQ-7 and Clevel constipation scores were also significantly different respectively(P<0.01).CONCLUSION: Laparoscopic partial sigmoidectomy combined with pelvic floor repair is an optional method in the treatment for pelvic floor dysfunction, which could effectively improve the constipation caused by dolichasigmoid and pelvic floor defect. It is also with low postoperative morbidity.

Objective:To investigate the differential expression and gene functions of up-regulated genes in rats with spinal cord injury. Methods:Female Sprague-Dawley rats' model of spinal cord injury was established with the modified Allen's method. Gene chip technology was used to detect the variation of differentially expressed genes in the spinal cord after spinal cord injury in rats. The differences in genes, functional localization and pathways were analyzed with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway database. Results:The results of total RNA quality in spinal cord segment were qualified. Gene chip results showed that there were 1874 differentially up-regulated genes and 2348 differentially down-regulated genes. Bioinformatics was used to analyze differentially up-regulated genes in terms of biological processes, cellular components, and molecular functions. The differentially up-regulated genes were involving apoptosis, immune response, inflammation, etc., pathway analysis mainly showed the differentially up-regulated genes involved phosphoinositide 3-kinase protein kinase B signaling pathway and Toll-like receptor signaling pathways. Conclusion:Differentially up-regulated genes may be involved in secondary reactions following spinal cord injury, such as inflammation, immune response and hypoxia, and then further affect motor function and sensory function.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib/therapeutic use* ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Multiple Myeloma/therapy* ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site