ABSTRACT
Objective: To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) . Methods: 42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ]. Results: In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively (P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively (P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion: The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.
Subject(s)
Bone Marrow , Chromosome Aberrations , In Situ Hybridization, Fluorescence , Multiple Myeloma , Humans , Multiple Myeloma/genetics , Multiple Myeloma/diagnosis , In Situ Hybridization, Fluorescence/methods , Immunoglobulin Light Chains/genetics , Male , Cytoplasm/metabolism , Middle Aged , FemaleABSTRACT
As an important force in promoting the transformation and upgrading of the national economy, the occupational health of the Internet industry's employees has received widespread attention. This paper examines the current situation of occupational health risks and management in the Internet industry at home and abroad, and on this basis reveals the physical and mental health problems of Internet industry employees. Combining the existing regulations, policies and standard documents at home and abroad, countermeasures are proposed to improve the relevant laws and regulations and their guidelines, implement relevant job design requirements, build a healthy working environment, optimise the work management system and carry out workplace health promotion, in order to provide ideas to accelerate the improvement of occupational health issues in the Internet industry.
Subject(s)
Internet , Occupational Health , Workplace , Humans , Industry , Health Promotion/methodsABSTRACT
Objective: To investigate the regulatory effect and mechanism of interleukin-22 (IL-22) on the gingival epithelial barrier in the context of periodontal inflammation. Methods: IL-22 knockout (IL-22 KO) mice were constructed, and periodontitis mice models were established through oral gavage with polymicrobial inoculation. DNAs were extracted from the oral plaques of IL-22 KO periodontitis mice group (n=7) and their wild-type littermates periodontitis group (n=7) to establish a periodontitis-related oral microbiota database"PD-RiskMicroDB", determining the relationship between changes in oral microbiota and microbial function in two groups using 16S rRNA sequencing results. Gingival epithelial cells (GEC) were cultured by modified trypsinization method, and were stimulated with 100 µg/L IL-22, Porphyromonas gingivalis (Pg) (multiplicity of infection:100), separately or together for 3 and 12 hours. The experimental groups were as follows: control group (no stimulation), IL-22 group, Pg group and Pg+IL-22 group. The expression of barrier protein E-cadherin in each group at 3 h was detected by immunofluorescence, real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Fluorescein isothiocyanate-dextran-mediated epithelial cell permeability experiment was conducted to clarify the changes in permeability of GEC in each group at 3 and 12 h. The mRNA expressions of E-cadherin in the gingival epithelium of wild-type littermates periodontitis group and IL-22 KO periodontitis group were detected by RT-qPCR. Fifteen C57BL/6 wild-type mice were randomly divided into control group (n=5), periodontitis group (n=5) and periodontitis+IL-22 treatment group (n=5). RT-qPCR and immunohistochemistry (IHC) staining were used to detect the expression level of E-cadherin in the gingival epithelium of each group. Results: 16S rRNA sequencing results showed that the composition of oral microbiota changed in IL-22 KO periodontitis group, of which the abundance of bacterial genera related to periodontal tissue invasion was significantly increased (linear discriminant analysis score: 2.22, P=0.009), compared with wild-type littermates periodontitis group. In vitro cell experiments showed that after Pg infection for 3 hours, the cell connections of GEC in Pg group were interrupted, and the fluorescence intensity of E-cadherin was reduced in Pg group compared with the control group. Meanwhile, the mRNA and protein expression levels of E-cadherin (mRNA: 0.69±0.12; protein: 0.60±0.12) were downregulated compared with the control group [mRNA: 1.00±0.00 (P=0.043); protein: 1.04±0.08 (P=0.003)], respectively. The fluorescence intensity of E-cadherin in the Pg+IL-22 group was enhanced compared with Pg group, and expression levels of E-cadherin mRNA (1.16±0.10) and protein (0.98±0.07) in Pg+IL-22 group showed a significant increase compared with Pg group [mRNA: 0.69±0.12 (P=0.005); protein: 0.60±0.12 (P=0.007)]. The result of epithelial permeability test showed that there was no statistical difference in epithelial permeability among control group, Pg group, IL-22 group and Pg+IL-22 group with treatment for 3 hours (F=0.20, P=0.893). While when the treatment time turned to be 12 hours, the epithelial barrier permeability showed a significant increase in Pg group (1.39±0.15) compared with control group (1.00±0.00, P=0.027), and a decrease in Pg+IL-22 group (1.02±0.18) compared with Pg group (1.39±0.15, P=0.034). In vivo, the mRNA expression of E-cadherin in the gingival epithelium of IL-22 KO periodontitis group decreased significantly (0.32±0.21) compared with wild-type littermates periodontitis group (1.01±0.01) (t=5.70, P=0.005). Moreover, RT-qPCR and IHC staining results showed that the mRNA expression level of E-cadherin (0.40±0.07) and absorbance value of E-cadherin positive expression (0.02±0.00) in gingival epithelial tissue of periodontitis group were both significantly down-regulated compared with control group [mRNA: 1.00±0.00 (P=0.005); absorbance value of E-cadherin positive expression: 0.04±0.01 (P=0.006)]. Meanwhile, the mRNA expression level of E-cadherin (1.06±0.24) and the absorbance value of E-cadherin positive expression (0.03±0.01) were both observed increase in periodontitis+IL-22 treatment group compared with periodontitis group (P=0.003, P=0.039). Conclusions: IL-22 may exert a protective effect on the gingival epithelial barrier in an inflammatory environment by regulating the invasiveness of oral microbiota and the expression of host barrier protein.
Subject(s)
Cadherins , Gingiva , Interleukin-22 , Interleukins , Mice, Knockout , Microbiota , Periodontitis , Porphyromonas gingivalis , Animals , Interleukins/metabolism , Cadherins/metabolism , Gingiva/cytology , Gingiva/metabolism , Gingiva/microbiology , Mice , Periodontitis/microbiology , Periodontitis/metabolism , Epithelial Cells/metabolism , RNA, Ribosomal, 16SABSTRACT
Objective: The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) . Methods: This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared. Results: â Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). â¡The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD (P=0.005). â¢No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM (R(2)=0.035, P=0.330). â£No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion: sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.
Subject(s)
B-Cell Maturation Antigen , Immunotherapy, Adoptive , Multiple Myeloma , Receptors, Chimeric Antigen , Humans , Multiple Myeloma/therapy , B-Cell Maturation Antigen/immunology , Receptors, Chimeric Antigen/immunology , Immunotherapy, Adoptive/methods , Bone Marrow/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Male , Middle Aged , FemaleABSTRACT
Objective: To analyze the consistency of the anesthesia index (AI) and Narcotrend index (NI) in monitoring the depth of anesthesia in pediatric tonsil/adenoidectomy. Methods: A total of 129 children who underwent elective tonsil/adenoidectomy at Xijing Hospital Affiliated to Air Force Medical University from July 2022 to October 2023 were prospectively enrolled. Both AI monitoring by ConView monitor and NI monitoring by Narcotrend monitor were conducted for children after they were admitted to the operating room, while Propofol-remifentanil combined with total intravenous anesthesia was used during the operation and the anesthetic dose was adjusted to maintain the NI value at 40-60. In addition, the AI and NI values were recorded at following time points: quiet eyes closing (T1), the beginning of induction (T2), loss of consciousness (T3), tracheal intubation (T4), the beginning of surgery (T5), during tonsil excision (T6), adenoidectomy (T7), the end of surgery (T8), consciousness recovery (T9) and tracheal extubation (T10). Bland-Altman consistency analysis was used to evaluate the consistency of the results of the two types of anesthesia depth monitoring, AI value and NI value. Receiver operator characteristic (ROC) curve and area under curve (AUC) were used to analyze the predictive efficacy of AI and NI values for the state of consciousness of children. The intraoperative awareness was followed up at 24 hours, 1 week and 1 month after surgery. Results: In 129 cases, there were 78 boys and 51 girls, with an average age of (7.2±3.2) years and an operation time of (72.8±14.0) min. No AI data were missing, but 13 NI data were missing, with a missing rate of 10.1% (13/129). At time points T1-T10, the AI values were 67.5±19.2 and the NI values were 67.2±19.2. Bland-Altman consistency analysis showed that the difference in value between AI and NI was 0.3 (95%CI:-0.1-0.6, P=0.120), with an out-of-consistency range of 4.0% (51/1 290). Before anesthesia induction, AI and NI values were maintained at a high level; with the beginning of anesthesia induction and the disappearance of the children's consciousness, both AI and NI values gradually decreased; after discontinuing the infusion of anesthetics, the values of AI and NI gradually increased, and the change trend of AI and NI in each stage of the perioperative period was consistent, and there was no significant difference between the two groups at each time point (all P>0.05). ROC curve analysis showed that the cut-off value for predicting the state of consciousness using AI was 72.5, with an AUC of 0.73 (95%CI: 0.70-0.75), and the cut-off value of NI was 79.5 and the AUC was 0.74 (95%CI: 0.72-0.77). There was no significant difference in AUC between the two indices (P=0.310). None of the children had intraoperative awareness. Conclusion: Both AI and NI can be used to monitor the depth of anesthesia in pediatric tonsil/adenoidectomy with high accuracy.
Subject(s)
Tonsillectomy , Humans , Tonsillectomy/methods , Child , Prospective Studies , Propofol/administration & dosage , Monitoring, Intraoperative/methods , Female , Remifentanil/administration & dosage , Male , Anesthesia/methods , Child, Preschool , Anesthetics, Intravenous/administration & dosageABSTRACT
The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.
Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/virology , Lymphohistiocytosis, Hemophagocytic/etiology , Male , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/diagnosis , Female , Adult , Retrospective Studies , Middle Aged , Antiviral Agents/therapeutic use , Young Adult , Aged , Cytomegalovirus , PrognosisABSTRACT
Objective: To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) . Methods: A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined. Results: After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly (P<0.001) between the POD<24 group (n=14) and the POD≥24 group (n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4-6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively (P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion: This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.
Subject(s)
Lymphoma, Extranodal NK-T-Cell , Humans , Lymphoma, Extranodal NK-T-Cell/drug therapy , Lymphoma, Extranodal NK-T-Cell/diagnosis , Retrospective Studies , Neoplasm Staging , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.
Subject(s)
Cervix Uteri , Sensitivity and Specificity , Tomography, Optical Coherence , Uterine Cervical Neoplasms , Humans , Female , Tomography, Optical Coherence/methods , Adult , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/diagnosis , Middle Aged , Cervix Uteri/diagnostic imaging , Cervix Uteri/pathology , Adolescent , Aged , Uterine Cervical Dysplasia/diagnostic imaging , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/diagnosis , Papillomavirus Infections/diagnosis , Young Adult , Vaginal Smears , Biopsy , Predictive Value of Tests , Early Detection of Cancer/methodsABSTRACT
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western adults, although the incidence of CLL is relatively low in Asian populations. However, with the aging population, the incidence of CLL is increasing in China. The interaction between CLL cells and the microenvironment plays a crucial role in the recognition of antigens by the B-cell receptor immunoglobulin (BCR IG). The mutational status of the immunoglobulin heavy variable region (IGHV) is a classical prognostic marker for CLL. Over 40% of CLL patients exhibit biased usage of IGHV and highly similar amino acid sequences in the heavy complementarity-determining region 3 (HCDR3), known as the BCR stereotypy. Different subgroups of stereotyped BCR exhibit distinct biological and clinical features. Among them, subset #2 with mutated IGHV and poor prognosis, as well as the subset #8 with a high risk of Richter transformation, have been recommended by the European Research Initiative on CLL to be included in clinical reports on IGHV mutational status. This review summarizes the definition, distribution, biological characteristics, and clinical significance of clonality patterns of the BCR in CLL.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Clinical Relevance , Complementarity Determining Regions/genetics , Immunoglobulin Variable Region/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Receptors, Antigen, B-Cell/genetics , Tumor MicroenvironmentABSTRACT
The occupational health issues of shift workers has received increasing attention in the field of occupational health, and discussed in this article through literature review on the health risks and management of shift work both domestically and internationally. Based on this, a series of impacts of shift work on the physiological and psychological health of workers, as well as their family and social life, are revealed. Combined with relatively mature regulations and policies in foreign countries, it is proposed that China should fully learn from the relevant experience of health management in shift work abroad, Strengthen research and explore effective management intervention measures to provide ideas for accelerating the development of scientifically feasible regulations and policies related to occupational health in shift work in China.
Subject(s)
Occupational Health , Shift Work Schedule , Humans , China , Work Schedule ToleranceABSTRACT
Objective: This study investigates the effect of signal-to-noise ratio (SNR), frequency, and bandwidth on horizontal sound localization accuracy in normal-hearing young adults. Methods: From August 2022 to December 2022, a total of 20 normal-hearing young adults, including 7 males and 13 females, with an age range of 20 to 35 years and a mean age of 25.4 years, were selected to participate in horizontal azimuth recognition tests under both quiet and noisy conditions. Six narrowband filtered noise stimuli were used with central frequencies (CF) of 250, 2 000, and 4 000 Hz and bandwidths of 1/6 and 1 octave. Continuous broadband white noise was used as the background masker, and the signal-to-noise ratio (SNR) was 0, -3, and -12 dB. The root-mean-square error (RMS error) was used to measure sound localization accuracy, with smaller values indicating higher accuracy. Friedman test was used to compare the effects of SNR and CF on sound localization accuracy, and Wilcoxon signed-rank test was used to compare the impact of the two bandwidths on sound localization accuracy in noise. Results: In a quiet environment, the RMS error in horizontal azimuth in normal-hearing young adults ranged from 4.3 to 8.1 degrees. Sound localization accuracy decreased with decreasing SNR: at 0 dB SNR (range: 5.3-12.9 degrees), the difference from the quiet condition was not significant (P>0.05); however, at -3 dB (range: 7.3-16.8 degrees) and -12 dB SNR (range: 9.4-41.2 degrees), sound localization accuracy significantly decreased compared to the quiet condition (all P<0.01). Under noisy conditions, there were differences in sound localization accuracy among stimuli with different frequencies and bandwidths, with higher frequencies performing the worst, followed by middle frequencies, and lower frequencies performing the best, with significant differences (all P<0.01). Sound localization accuracy for 1/6 octave stimuli was more susceptible to noise interference than 1 octave stimuli (all P<0.01). Conclusions: The ability of normal-hearing young adults to localize sound in the horizontal plane in the presence of noise is influenced by SNR, CF, and bandwidth. Noise with SNRs of ≥-3 dB can lead to decreased accuracy in narrowband sound localization. Higher CF signals and narrower bandwidths are more susceptible to noise interference.
Subject(s)
Sound Localization , Speech Perception , Male , Female , Humans , Young Adult , Adult , Noise , Signal-To-Noise Ratio , HearingABSTRACT
Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
Subject(s)
Liver Neoplasms , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Female , Retrospective Studies , Middle Aged , Aged , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Adult , Prognosis , Survival Rate , Aged, 80 and over , Proportional Hazards Models , Palliative Care , Kaplan-Meier Estimate , Hepatectomy/methods , Treatment OutcomeABSTRACT
Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma originating from the thymus, which has different clinical and biological characteristics from diffuse large B-cell lymphoma, NOS. PMBCL tends to occur in young women, usually presenting as a large anterior mediastinal mass. Most patients are in stage â -â ¡ at the time of presentation. There is no standard prognostic scoring system for PMBCL. Immunochemotherapy is commonly used in the treatment of PMBCL, but the optimal first-line treatment has not been determined, and the status of radiotherapy is controversial. The value of PET-CT guided therapy needs to be further verified. Relapsed/refractory PMBCL has a poor prognosis, while novel therapies such as PD-1 inhibitors, brentuximab vedotin, and CAR-T can help improve survival in these patients.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Mediastinal Neoplasms , Adult , Humans , Female , Positron Emission Tomography Computed Tomography , Prognosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immunotherapy , Mediastinal Neoplasms/drug therapy , Mediastinal Neoplasms/pathologyABSTRACT
This article focuses on a case study of sitosterolemia in a child who initially presented with hemolytic anemia and thrombocytopenia. Sitosterolemia is a rare autosomal recessive lipid metabolism disorder, difficult to diagnose due to its non-typical clinical manifestations. The 8-year-old patient was initially misdiagnosed with pyruvate kinase deficiency. Comprehensive biochemical and molecular biology analyses, including gene sequencing, eventually led to the correct diagnosis of sitosterolemia. This case highlights the complexity and diagnostic challenges of sitosterolemia, emphasizing the need for increased awareness and accurate diagnosis in patients presenting with similar symptoms.
Subject(s)
Anemia, Hemolytic , Hypercholesterolemia , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Phytosterols/adverse effects , Thrombocytopenia , Child , Humans , Hypercholesterolemia/diagnosis , Hypercholesterolemia/genetics , Phytosterols/genetics , Anemia, Hemolytic/diagnosis , Intestinal Diseases/diagnosis , Intestinal Diseases/genetics , Thrombocytopenia/diagnosisABSTRACT
Objective: To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype. Methods: This case series study was performed on pediatric patients who were referred to the Children's Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples. Results: A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions: Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.
Subject(s)
Rubinstein-Taybi Syndrome , Male , Female , Child , Humans , Child, Preschool , Rubinstein-Taybi Syndrome/genetics , Rubinstein-Taybi Syndrome/diagnosis , DNA Copy Number Variations , Genotype , Phenotype , Genetic Testing , CREB-Binding Protein/genetics , MutationABSTRACT
Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.
Subject(s)
Cytopenia , Lymphopenia , Multiple Myeloma , Neutropenia , Receptors, Chimeric Antigen , Thrombocytopenia , Female , Humans , Male , Anemia , Antibodies/therapeutic use , B-Cell Maturation Antigen/therapeutic use , Multiple Myeloma/therapy , Prognosis , Receptors, Chimeric Antigen/therapeutic use , Retrospective Studies , Middle Aged , AgedABSTRACT
Objective: To summarize the imaging presentations of the fallopian canal cerebrospinal fluid leaking (FCCFL). Methods: The high resolution CT (HRCT)and MRI materials of 4 patients (4 ears) with FCCFL confirmed by surgery between August 2016 to November 2023 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 6 to 69 years. Results: All of the FCCFL were unilateral, including 2 on the left and 2 on the right.Clinically, the patients with FCCFL suffered from clear nasal fluid flow, ear tightness, and hearing loss. On CT, all of the affected ears were depicted markedly dilatation of the proximal portion of fallopian canal(FC), the labyrinthine segment and geniculate fossa were involved in 4 cases, and involvement of tympanic segment in 1 case at the same time. The geniculate fossa in the affected side were significantly enlarged, protruding upwards into the tympanic cavity, with one case simultaneously involving the cochlea. On MRI, the hyposignal on T1WI and hypersignal on T2WI or water sequence like cerebrospinal fluid (CSF) were shown in the enlargement FC, without diffusion restriction, and non-enhancing with administration Gadolinium contrast.CSF-like signal effusion was shown in all of the affected tympanum, of which, the CSF-like signal effusion was demonstrated in the area along the superficial petrosal nerve, the right pterygopalatine fossa and the parapharyngeal space. The adjacent intracranial meninges were presented thickening in 3 cases. Conclusion: The imaging appearances of FCCFL present some characteristics:on HRCT, the proximal portions of the affected FC depicts markedly enlargement,especially the geniculate fossa.While they present CSF-like signal, no diffusion restriction, and no enhancement administration, Gadolinium contrast on MRI, accompanying the CSF-like signal effusion in the affected tympanum.
Subject(s)
Ear, Inner , Temporal Bone , Male , Female , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Retrospective Studies , Gadolinium , Ear, Inner/diagnostic imaging , Ear, Middle , Magnetic Resonance Imaging , Cerebrospinal Fluid Leak/diagnostic imagingABSTRACT
The risk management in workplace is an important measure to effectively prevent and control the harm of hand-transmitted vibration. Based on the relevant developments at home and abroad, this paper expounds the risk of manual vibration operation in workplace by taking contact assessment and hazard assessment as an example. On this basis, the limit management and hierarchical management related to risk management are discussed, and the existing problems are analyzed.
Subject(s)
Occupational Exposure , Vibration , Vibration/adverse effects , Hand , Workplace , Risk ManagementABSTRACT
Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.
Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Male , Female , Humans , Middle Aged , Prognosis , Multiple Myeloma/therapy , Multiple Myeloma/diagnosis , Treatment Outcome , Oligoclonal Bands/therapeutic use , Retrospective Studies , Transplantation, Autologous , Stem Cell TransplantationABSTRACT
The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.