Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

ObjectiveTo conduct a systematic comparative study on wild and cultivated Codonopsis pilosula（CP） from three aspects， including characters， microscopy， and contents of primary and secondary metabolites. MethodWild and cultivated CP samples were collected， their characters were measured using vernier caliper， tape measure and balance， the paraffin sections were stained with safranin-fixed green dyeing， and their microstructure were observed under the optical microscope. The content of alcohol-soluble extracts in wild and cultivated CP was determined according to the method for determination of extract under CP in the 2020 edition of Chinese Pharmacopoeia， the starch content was determined by anthrone colorimetry， the content of total polysaccharides was determined by kit method， Fiber analyzer was used to determine the content of fiber components， and ultra performance liquid chromatography（UPLC） was used to determine the content of monosaccharides， disaccharides and some secondary metabolites. Multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were employed to screen key differential components between wild and cultivated CP on the basis of variable importance in the projection（VIP） value>1 and P<0.05. ResultIn terms of morphological characteristics， the "lion's head-like" shape， longitudinal wrinkles， and circumferential wrinkles below the root cap of wild CP were more pronounced in wild CP compared to the cultivated ones. Regarding transverse sectional features， wild CP had more fissures on the outer side of the cortex and a larger duramen. Under microscopic examination， wild CP had more stone cells， a larger proportion of xylem， and the presence of cork cells arranged in rings in the xylem， while cultivated CP has a larger proportion of phloem， smaller vessel diameters， and a more loosely arranged vascular system. In terms of primary metabolites， the contents of 45% ethanol-soluble extract and total polysaccharides in cultivated CP were significantly higher than those in the wild ones（P<0.05）， the contents of lignin， hemicellulose， cellulose， fructose and glucose in wild CP were significantly higher than those in the cultivated ones（P<0.05）， while sucrose content in the cultivated CP was significantly higher than that in the wild ones（P<0.05）. Concerning secondary metabolites， the contents of tryptophan and tangshenoside Ⅰ in cultivated CP were significantly higher than those in the wild ones（P<0.05）， whereas the contents of lobetyolinin， lobetyol and atractylenolide Ⅲ in wild CP were significantly higher than those in the cultivated ones（P<0.05）. ConclusionThere are significant differences between wild and cultivated CP in terms of morphological characteristics， microscopic features and chemical composition. Glucose， fructose， sucrose， tangshenoside Ⅰ， tryptophan and cellulose components are the key differential components between wild and cultivated CP. Wild CP contains more polyacetylenes and fructose， whereas cultivated CP has higher levels of tangshenoside Ⅰ and sucrose， with noticeably lower cellulose content. These distinctions may be related to their growth conditions， growth years and cultivation techniques. Based on the results of this study， it is recommended to increase polyacetylenes and the content ratio of fructose to sucrose as an indicators to characterize different production methods of CP， in order to guide the high-quality production of CP.

Objective:To understand the prevalence of tobacco use in middle school students in Fujian in 2019 and 2021, explore the influencing factors associated with tobacco use and provide data support for tobacco control intervention.Methods:Two surveys were conducted in middle school students selected through multi-stage stratified clustering random sampling from 10 counties (districts) of Fujian in 2019 and 2021, and χ2 test was used to examine the differences in prevalence of tobacco use between two years, and multiple logistic regression analysis models were used to analyze the factors associated with the tobacco use. Results:The current smoking rate was 2.9% in middle school students in Fujian in 2021, lower than that in 2019 (4.3%). The rate of smoking attempt was higher in 2021 (15.2%) than in 2019 (13.4%). The rate of passive smoking exposure at home, indoor public place, outdoor public place and public transport in 2021 (51.1%) was lower than in 2019 (62.8%), the differences were significant (all P<0.001). In 2021, being vocational school student, passive smoking exposure, believing that smoking is an attractive behavior, believing that smoking is helpful for social contact and seeing other people smoking, including close friends and teachers, were positive associated with tobacco use. Students who believed that passive smoke is harmful and smoking is difficult to quit had lower current smoking rate and smoking attempt rate, respectively. Conclusions:Although the current smoking rate declined in middle school students in Fujian, the smoking attempt rate increased. We should strengthen the establishment of smoke-free campus, health education about tobacco use control to protect adolescents from the harm of tobacco use.

Objective:To analyze the correlation between nasal resistance and lung function in children with allergic rhinitis（AR）, and explore whether AR children with increased nasal resistance are accompanied by potential lower respiratory tract involvement. Methods:A total of 88 children diagnosed with AR from December 2021 to December 2022 were selected as the study group, while 20 normal children were selected as the control group during the same period. Both the study group and the control group children underwent lung function tests, bronchodilator tests, and nasal resistance measurements. Spearman correlation analysis and multiple linear regression analysis were performed on the results of nasal resistance and lung function tests to explore the relationship and influencing factors between the two groups.According to the results of nasal resistance measurement, children with increased nasal resistance and abnormal lung function were divided into a mild increase in nasal resistance with abnormal lung function group and a moderate to severe increase in nasal resistance with abnormal lung function group. The degree of increased nasal resistance was analyzed to determine whether it would affect lung function. Results:The FEF25, FEF50, and FEF75 levels in the study group were significantly lower than those in the control group（P<0.05）. The FEV1of children with moderate to severe increase in AR nasal resistance was significantly lower than that of children with mild increase in AR nasal resistance（P<0.05）. There was a correlation between nasal resistance and FEV1/FVC, R20 in AR children, and FEV1/FVC, R20 were the influencing factors of nasal resistance in AR children（P<0.05）. There was no correlation between total serum IgE, lung function, and bronchodilation test in AR patients（P>0.05）. Conclusion:The nasal ventilation function of AR patients has changed, and there is a downward trend in small airway function. Children with moderate to severe increase in AR nasal resistance have a more significant decrease in lung ventilation function than those with mild increase. The nasal resistance of AR children is influenced by FEV1/FVC and R20, and FEV1/FVC and R20 decrease as the nasal resistance value increases. The improvement rate of lung function and FEV1 are not influencing factors for the elevation of total serum IgE.
Humans ; Child ; Rhinitis, Allergic/diagnosis* ; Nasal Polyps ; Respiratory Function Tests ; Nose ; Immunoglobulin E

Objective:To examine the survival and influential factors of an integrated approach of novel agents, autologous hematopoietic stem cell (auto-HSCT) , and maintenance therapy in patients with multiple myeloma (MM) patients from a single center over the past 15 years.Methods:In our center, 300 MM patients who received an integrated strategy of new agents, auto-HSCT, and maintenance therapy over 15 years were retrospectively and prospectively analyzed.Results:The complete remission rates (CR) and ≥very good partial remission rates (VGPR) following induction therapy, transplantation, and maintenance therapy were respectively 35.3% and 55.2% , 72.4% and 80.0% , 89.2% , and 93.4% . When compared to patients receiving double-drug induction, the ≥VGPR and ORR of patients receiving triple-drug induction were improved. No difference existed in CR, ≥VGPR, and ORR between the PAD (bortezomib + liposome doxorubicin+ dexamethasone) and RAD (lenalidomide + liposome doxorubicin + dexamethasone) regimens, but the benefits speed differed. The negative rate of flow minimal residual disease following induction, transplantation, and maintenance was 18.8% (54 cases) , 41.4% (109 cases) , and 58.7% (142 cases) , respectively. The median time to progress (TTP) was 78.7 months and the median overall survival (OS) was 109 months. The median TTP for RISS-Ⅰ-Ⅲ patients were 111.8 months, 77.4 months, and 30.6 months, and the median OS was 118.8 months, 91.4 months, and 48.5 months, respectively. At various points during treatment, the TTP and OS of patients obtaining CR and MRD negative were longer than those of patients who did not obtain CR and MRD negative. TTP was noticeably shorter in high-risk cytogenetic patients compared to standard-risk patients even when CR was acquired during induction. There was no difference in TTP between patients with high-risk cytogenetics and those with standard-risk cytogenetics if MRD negative was acquired during induction. According to a multivariate analysis, the R-ISS stage was a poor predictor of TTP and OS at various treatment intervals. Therapeutic effectiveness was a newly independent prognostic factor following treatment.Conclusion:A median survival of almost 10 years is possible for MM patients who receive an integrated strategy of induction regimens followed by auto-HSCT and maintenance therapy, which significantly improves prognosis. However, this approach did not significantly benefit high-risk cytogenetic MM patients.

Objective To determine the genotype and clustering characteristics of multidrug-resistant (MDR) mycobacterium tuberculosis in Wuhan City. Methods A total of 149 mycobacterium tuberculosis strains from MDR tuberculosis (MDR-TB) patients were genotyped by DTM-PCR, mycobacterial interspersed repetitive unit–variable number tandem repeat typing (MIRU-VNTR) and sequencing of drug-resistant associated genes. The Hunter-Gaston discriminatory index (HGDI), clustering rate and recent minimum estimated infection rate were calculated. Results The cumulative HGDI of all MIRU loci was 0.9944. Gene locus with the highest HGDI（0.6467）was QUB11b. Combing MIRU-VNTR and DTM-PCR, 111 unique genotypes and 11 clustered genotypes（38 strains）from 149 isolates were identified. The clustering rate was 25.50%, and the recent minimum infection rate was estimated to be 18.12%. After further genotyping by sequencing of drug-resistant associated genes, the results showed that 17 (44.74%) strains in each cluster shared the same mutation sites, while the other strains had different mutation sites. Conclusion The combination of DTM-PCR, 24 locus MIRU-VNTR typing and drug resistance gene sequencing demonstrates a relatively high discriminatory power, which is suitable for the genotyping of multi drug resistant mycobacterium tuberculosis in Wuhan. The epidemic of MDR-TB in Wuhan is mainly caused by reactivation, and the recent transmission rate is not high.

Objective:To investigate the relationship between peritoneal thickness and baseline solute transport function in peritoneal dialysis (PD) patients, and analyze the factors affecting the function of peritoneal transport.Methods:Non-diabetic end-stage renal disease (ESRD) patients admitted to the Second Hospital of Longyan City from January 2017 to June 2019 were enrolled in this study. The thickness of the peritoneal membrane was measured by color ultrasound instrument before the peritoneal catheterization. Standard peritoneal equilibration test (PET) was performed after one month of peritoneal dialysis. The ratio of corrected creatine in 4 h dialysate to 2 h serum creatine (D/Pcr) was used as a solute baseline transport index, and according to the D/Pcr evaluation results, the patients were divided into high/high average transfer (H) group (D/Pcr≥0.65) and low/low average transfer (L) group (D/Pcr<0.65). The clinical data, peritoneal thickness and peritoneal dialysis related indicators between the two groups of patients were compared. Binary logistic regression was used to analyze the factors affecting the function of peritoneal transport.Results:The amount of peritoneal ultrafiltration in H group was significantly lower than that in L group, intraperitoneal creatinine clearance (Ccr) and peritoneal thickness were significantly higher than those in L group (both P<0.05). Pearson and Spearman correlation results showed that the thickness of peritoneal membrane positively correlated with D/Pcr ( r=0.673, P<0.05), peritoneal Ccr ( r=0.261, P<0.05), and negatively correlated with ultrafiltration of peritoneal dialysis ( r=-0.365, P<0.05). Partial correlation analysis showed that the peritoneal thickness was positively correlated with the solute transport index D/Pcr ( r=0.539, P<0.05) and the peritoneal Ccr ( r=0.338, P<0.05). Binary logistic regression results showed that peritoneal thickening was a risk factor affecting peritoneal transport function ( OR=1.175, 95% CI 1.009-1.369, P<0.05). Conclusions:There is a positive correlation between the peritoneal membrane thickness and the baseline solute transport index in patients with non-diabetic peritoneal dialysis. Peritoneal thickening is a risk factor affecting peritoneal transport function.

Fatigue is the second most common symptom in patients with chronic obstructive pulmonary disease (COPD) . It has a high incidence and interferes with patients' normal working life. This article reviews the concept and pathogenesis of fatigue, as well as the predisposing factors and treatments of fatigue symptom in patients with COPD. This article provides a reference for medical staff to deepen their understanding of fatigue in order to take effective measures to relieve fatigue and improve patients' quality of life.

Objective To investigate the effects of rotavirus ( RV) on the expression and bioactiv-ity of Na+-H+ exchanger 3 ( NHE3 ) in Caco-2 cells and the possible regulatory mechanism. Methods Caco-2 cells expressing NHE3 were constructed and divided into four groups as follows: control ( CTL ) group, RV group, BAPTA-AM ( a Ca2+ chelator) group and BAPTA-AM+RV group. Na+-H+ exchanger ac-tivity and NHE3 expression on cell surface were determined using BCECF-AM and biotinylation assay, re-spectively. Expression of Cdc42 at protein level was measured by Western blot. Results Compared with the control group, RV infection significantly decreased the activity of NHE3 and its expression on cell surface. BATPA-AM antagonized the inhibitory effects on NHE3. Moreover, the expression of Cdc42 at protein level was increased following RV infection, which was also antagonized by BATPA-AM. Conclusions Intracellu-lar Ca2+-mediated Cdc42-dependent endocytosis pathway might be involved in regulating the expression and bioactivity of NHE3 during RV infection.

Objective: To investigate the survival time of multidrug-resistant tuberculosis (MDR-TB) patients and the influential factors in Wuhan. Methods: The relevant information were collected from TB management information system, cause of death reporting system and medical records by trained doctors. The univariate and multivariate Cox proportional hazards model were applied to analyze the factors affecting survival time of patients. Results: A total of 552 patients with MDR-TB were included in the analysis. After the diagnosis of MDR-TB, the cumulative survival rates from the first year to the third year were 0.94, 0.88, and 0.80, respectively. The mortality density of MDR-TB patients was 6.52/100 person-years, and the median survival time was (89.52±1.85) months. Kaplan-Meier analysis showed that the cumulative survival rate of the standardized treatment group was significantly higher than that of the non-standardized treatment group (Log rank=101.070, P<0.001). Compared with the patients aged <30 years, the HR of the patients aged 30-years and ≥60 years were 2.987 (95%CI: 1.268-7.036), 4.957 (95%CI: 1.942-12.653). Compared with the patients with the education level of high school and above, the HR of the patients with education level of junior high school/primary school and below were 1.908 (95%CI: 1.152-3.160), 1.681(95%CI: 1.033-2.735). Compared with the patients without diabetes, the HR of the patients with diabetes was 1.961(95%CI: 1.347-2.854). Compared with the patients without other serious diseases, the HR of the patients with other serious diseases was 2.597 (95%CI: 1.820-3.706). Compared with the patients who had been treated less than one time, the HR of the patients having previous treatment with more than 2 times was 1.611 (95%CI: 1.077-2.409). Compared with patients receiving standard MDR regimen treatment, the HR of the patients receiving no standard MDR regimen treatment was 3.155 (95%CI: 2.132-4.670). Conclusions The cumulative survival rate of MDR-TB patients without standard treatment was significantly lower than that of patients with standard treatment. Older age, low educational level, diabetes mellitus, other serious diseases, more than two times treatment in the past, and receiving no multi-drug resistance regimen treatment were the risk factors affecting the survival of MDR-TB patients.