[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

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.

[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma].

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

[Clinical application of split liver transplantation: a single center report of 203 cases].

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

[Multivariable analysis of tooth loss in subjects with severe periodontitis over 4-year natural progression].

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION: In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.

Altered resting-state functional connectivity between subregions in the thalamus and cortex in migraine without aura.

BACKGROUND AND PURPOSE: Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes. METHODS: A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed-based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions. RESULTS: The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R-IPL) and right middle frontal gyrus. Furthermore, the FC Z-scores between the VPN and R-IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z-scores between the VPN and R-IPL. CONCLUSION: These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R-IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity.

Ultra-narrow linewidth quantum dot coherent comb lasers with self-injection feedback locking.

We have used an external cavity self-injection feedback locking (SIFL) system to simultaneously reduce the optical linewidth of over 39 individual wavelength channels of an InAs/InP quantum dot (QD) coherent comb laser (CCL). Linewidth reduction from a few MHz to less than 200 kHz is observed. Measured phase noise spectra clearly indicate a significant decrease in phase noise in the frequency range above 2 kHz. The RF beating signal between two adjacent channels also shows a substantial reduction in 3-dB linewidth from 10 kHz to 300 Hz with the SIFL system, and a corresponding drop in baseline level (-27 dB to -50 dB).

High performance InAs/InP quantum dot 34.462-GHz C-band coherent comb laser module.

We have developed an InAs/InP quantum dot (QD) C-band coherent comb laser (CCL) module with actively stabilized absolute wavelength and power, and channel spacing of 34.462 GHz with ± 100 ppm accuracy. The total output power is up to 46 mW. The integrated average relative intensity noise (RIN) values of the lasing spectrum and a filtered single channel at 1540.19 nm were -165.6 dB/Hz and -130.3 dB/Hz respectively in the frequency range from 10 MHz to 10 GHz. The optical linewidth of the 45 filtered individual channels between 1531.77 nm to 1543.77 nm ranged from 850 kHz to 2.16 MHz. We have also analyzed the noise behaviors of each individual channel.

The microRNA expression profile in porcine skeletal muscle is changed by constant heat stress.

Heat stress has profound effects on animal performance and muscle function, and microRNAs (miRNAs) play a critical role in muscle development and stress responses. To characterize the changes in miRNAs in skeletal muscle responding to heat stress, the miRNA expression profiles of longissimus dorsi muscles of pigs raised under constant heat stress (30 °C; n = 8) or control temperature (22 °C; n = 8) for 21 days were analyzed by Illumina deep sequencing. A total of 58 differentially expressed miRNAs were identified with 30 down-regulated and 28 up-regulated, and 63 differentially expressed target genes were predicted by miRNA-mRNA joint analysis. GO and KEGG analyses showed that the genes regulated by differentially expressed miRNAs were enriched in glucose metabolism, cytoskeletal structure and function and stress response. Real-time PCR showed that the mRNA levels of PDK4, HSP90 and DES were significantly increased, whereas those of SCD and LDHA significantly decreased by heat exposure. The protein levels of CALM1, DES and HIF1α were also significantly increased by constant heat. These results demonstrated that the change in miRNA expression in porcine longissimus dorsi muscle underlies the changes in muscle structure and metabolism in porcine skeletal muscle affected by constant heat stress.

[Levels of Galectin-7 in serum and sputum in children with asthma].

Objective: To observe the expression of Galectin-7 in the serum and sputum of asthmatic children and to explore its significance in asthmatic children. Methods: The study prospectively case-control selected 183 children diagnosed with bronchial asthma at Department Ⅱ of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital of Capital Medical University. The control group consisted of 41 children with other bronchial diseases and 43 healthy children. Children in the asthma group were divided into acute and non-acute exacerbation groups. Acute exacerbation group was divided as mild acute, moderate acute and severe acute groups; non-acute exacerbation group was divided as mild persistent, moderate persistent and severe persistent groups. Children without acute exacerbation asthma in the asthma group were divided into high and low Galectin-7 groups based on median serum Galectin-7 levels. Serum and sputum were collected, Galectin-7 levels were measured using enzyme-linked immunosorbent assay. The study compared and analyzed the differences in Galectin-7 levels between children with asthma and the control groups using Mann-Whitney U test or the Kruskal-Wallis or the Chi-square test for inter-group comparisons. Results: Among 183 children, 61 cases had acute asthma exacerbation, and 122 cases had persistent asthma without acute exacerbation. The asthma group comprised 110 males and 73 females. The control group consisted of 41 children with other bronchial diseases, including 24 cases of bronchiectasis and 17 cases of obliterans bronchitis. The control group comprised 26 males and 15 females. Forty-three healthy children who underwent physical examination, including 22 males and 21 females. The levels of Galectin-7 in serum were significantly higher in children with an acute asthma exacerbation than that of healthy children (0.1 (0, 0.7) vs. 0 (0, 0.2) µg/L, Z=2.09, P=0.001). Galectin-7 levels in sputum were higher in children with an acute asthma exacerbation than that in children with other bronchial diseases (1.2 (0.1,3.7) vs. 0.4 (0.1, 1.5) µg/L, Z=2.20, P<0.001). Serum Galectin-7 levels were significantly higher in children with persistent asthma compared to children with other bronchial diseases and healthy children (0.6 (0.3, 1.2) vs. 0.1 (0, 0.5) and 0 (0, 0.2) µg/L, Z=-6.12,-7.63, both P<0.001), and the levels were significantly and positively correlated with asthma severity (r=0.77, P<0.001), disease duration (r=0.34, P=0.001), and number of previous attacks (r=0.51, P<0.001). There were 61 children in the high-Galectin-7 group and 61 children in the low-Galectin-7 group. Children with high Galectin-7 had more asthma triggers, a greater proportion with a positive family history, more previous asthma attacks, longer duration of asthma, and higher serum total IgE levels compared to those with low Galectin-7 (χ2=9.30, 22.46, Z=5.06, 3.57, 2.31, all P<0.05). Conclusion: The expression of Galectin-7 is found to be elevated in the serum and sputum of asthmatic children and correlated with asthma conditions.

[Clinical phenotyping of severe Mycoplasma pneumoniae pneumonia in children].

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children's Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Role of glycogen synthase kinase-3ß in ketamine-induced developmental neuroapoptosis in rats.

BACKGROUND: Ketamine-induced neuroapoptosis has been attributed to diverse stress-related mechanisms. Glycogen synthase kinase-3ß (GSK-3ß) is a multifunctional kinase that is active in neuronal development and linked to neurodegenerative disorders. We hypothesized that ketamine would enhance GSK-3ß-induced neuroapopotosis, and that lithium, an inhibitor of GSK-3ß, would attenuate this response in vivo. METHODS: Protein levels of cleaved caspase-3, protein kinase B (AKT), GSK-3ß, and cyclin D1 were measured in post-natal day 7 rat pups after 1.5, 3, 4.5, and 6 h exposure to ketamine. A cohort of rat pups was randomized to a 6 h exposure to ketamine with and without lithium. Neuroapoptosis was measured by cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling staining by immunohistochemistry. Protein levels of cleaved caspase-3 and -9 and the total and phosphorylated forms of AKT, GSK-3ß, and cyclin D1 (cell cycle protein) were also measured. RESULTS: Ketamine produced a duration-dependent increase in cleaved caspase-3 and cyclin D1, which corresponded to decreases in phosphorylated AKT and GSK-3ß. Co-administration of lithium with ketamine attenuated this response. CONCLUSIONS: Ketamine-induced neuroapoptosis is associated with a temporal decrease in GSK-3ß phosphorylation, and simultaneous administration of lithium mitigated this response. These findings suggest that GSK-3ß is activated during this ketamine-induced neuroapoptosis.

[Predictive factors for sequelae of bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia].

Objective: To investigate the predictive factors for bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods: A restrospective case summary was conducted 230 patients with RMPP admitted to the Department of No.2 Respiratory Medicine of Beijing Children's Hospital, Capital Medical University from January 2013 to June 2017 were recruited. Clinical data, laboratory results, imaging results and follow-up data were collected. Based on bronchoscopy and imaging findings 1 year after discharge, all patients were divided into two groups: one group had sequelae of bronchitis obliterans (sequelae group) and the other group had not bronchitis obliterans (control group), independent sample t-test and nonparametric test were used to compare the differences in clinical features between the two groups. Receiver operating characteristic (ROC) curve to explore the predictive value of Bronchitis Obliterans in RMPP. Results: Among 230 RMPP children, there were 115 males and 115 females, 95 cases had sequelae group, the age of disease onset was (7.1±2.8) years;135 cases had control group, the age of disease onset was (6.8±2.7) years. The duration of fever, C-reative protein (CRP) and lactate dehydrogenase (LDH) levels, the proportion of ≥2/3 lobe consolidation, pleural effusion and the proportion of airway mucus plug and mucosal necrosis were longer or higher in the sequelae group than those in the control group ((17±9) vs. (12±3) d, (193±59) vs. (98±42) mg/L,730 (660, 814) vs. 486 (452, 522) U/L, 89 cases (93.7%) vs. 73 cases (54.1%), 73 cases (76.8%) vs.59 cases (43.7%), 81 cases (85.3%) vs. 20 cases (14.8%), 67 cases (70.5%) vs. 9 cases (6.7%), t=5.76, 13.35, Z=-6.41, χ2=14.64, 25.04, 22.85, 102.78, all P<0.001). Multivariate Logistic regression analysis showed that the duration of fever ≥10 days (OR=1.200, 95%CI 1.014-1.419), CRP levels increased (OR=1.033, 95%CI 1.022-1.044) and LDH levels increased (OR=1.001, 95%CI 1.000-1.003) were the risk factors for sequelae of bronchitis obliterans in RMPP. ROC curve analysis showed that CRP 137 mg/L had a sensitivity of 82.1% and a specificity of 80.1%; LDH 471 U/L had a sensitivity of 62.7% and a specificity of 60.3% for predicting the development of bronchitis obliterans. Conclusions: The long duration of fever (≥10 d), CRP increase (≥137 mg/L) may be used to predict the occurrence of sequelae of bronchitis obliterans in RMPP. It is helpful for early recognition of risk children.

[Clinical features of children with post-primary tuberculosis].

Objective: The aim of this study was to summarize the clinical and imaging characteristics of post-primary tuberculosis in children, so as to improve the early identification and diagnosis of post-primary tuberculosis. Methods: This was a retrospective study which enrolled children who were admitted to the Department No.2 of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University between January 2015 to December 2020 and with a diagnosis of post-primary tuberculosis. Results: A total of 30 patients were enrolled, including 10 males and 20 females. The age on admission were 13.0 (12.0, 13.3) years. Their common symptoms were cough and fever, there were 26 cases (87%) with cough and 23 cases (77%) with fever, but only 4 cases (13%) had other toxic symptoms (night sweat, weakness or weight loss) of tuberculosis other than fever. Blood examination showed that the white blood cell count was (10±3)×109/L, accompanied by elevated proportion of neutrophils (0.69±0.11) and increased level of C-reactive protein (31 (15,81) mg/L). The common radiographic findings of CT were nodular or mass shadow with cavitation (19 cases (63%)), consolidation (13 cases (43%)), bronchogenic spread (12 cases (40%)), hilar or mediastinal lymphadenopathy (5 cases (17%)) in this cohort. The affected locations included the right upper lobe (21 cases (70%)), the left lower lobe (17 cases (57%)) and the right lower lobe (15 cases (50%)). Acid-fast bacillus smears and mycobacterial cultures were attempted for all cases, resulting in 33% (10/30) with smear positivity and 50% (15/30) with culture positivity. Conclusions: Post-primary tuberculosis in children has no specific clinical manifestations. Imaging of chest CT is mainly manifested as nodular shadow with cavitation, consolidation or bronchogenic spread. Accurate identification of post-primary tuberculosis is crucial for preventing the spread and early treatment of tuberculosis.

[Efficacy and safety of autologous hematopoietic stem cell transplantation in elderly multiple myeloma patients: a single center retrospective study].

Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.

[New agents-based induction chemotherapy followed by autologous stem cell transplantation and maintenance treatment strategy for multiple myeloma: a single center retrospective study of 300 cases].

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.

Two novel mutations in the Spastin gene of Chinese patients with hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative diseases. Mutations in the spastin (SPG4) gene are responsible for approximately 40% of autosomal dominant HSP (AD-HSP) and 6.5-18% of sporadic cases. METHODS: Spastin mutations were screened in 11 AD-HSP families and 11 sporadic cases by direct sequencing and MLPA assay. Novel mutations were detected in 100 healthy controls by PCR-RFLP. RESULTS: We identified seven different spastin mutations in five probands and one sporadic patient. Two of seven mutations were novel. The c.458delT was a pathogenic mutation, but the effect of c.1724 G>T remained unknown. CONCLUSIONS: This study allowed us to estimate the frequency of the SPG4 mutations in Chinese at 45% (5/11) in families with AD-HSP and 9% (1/11) in sporadic cases. In addition, our data showed p.T614I was not associated with congenital arachnoid cysts.

Identification of lactic acid bacteria in Taiwanese ropy fermented milk and evaluation of their microbial ecology in bovine and caprine milk.

The purpose of this study was to identify species of lactic acid bacteria in Taiwanese ropy fermented milk and to study their microbial dynamics during the fermentation process through conventional microbiological cultivation and PCR-denaturing gradient gel electrophoresis. Identification results indicated that Lactococcus lactis ssp. cremoris and Leuconostoc mesenteroides ssp. mesenteroides were the major lactic acid bacteria in Taiwanese ropy fermented milk. Interestingly, 3 groups were identified as Lc. lactis ssp. cremoris using 16S rDNA sequencing, but they showed different denaturing gradient gel electrophoresis patterns and assimilation of carbohydrates. In addition, the microbial dynamics study in different fermentation stages demonstrated that Lc. lactis ssp. cremoris was the most dominant bacterial species in the samples, followed by Leu. mesenteroides ssp. mesenteroides with no differences among the fermentation stages. Finally, the microbial distribution profiles showed that the microbial ecology was different in bovine, caprine, and reconstituted milk, which might further affect the characteristics of the product.

[Clinical features and early diagnostic clues of chronic granulomatous disease].

Objective: To explore the early clinical clues for diagnosis of chronic granulomatous disease (CGD). Methods: One hundred and thirty-nine children with CGD seen in Beijing Children's Hospital from January 2007 to October 2020 were included in this study. The clinical features including age of onset, first presentations, reason for being hospitalized, etiology, imaging features, clues for early diagnosis of all patients were evaluated retrospectively. According to the time of diagnosis, the patients were divided into two groups, cases diagnosed before 2015 and after 2015 and 2015. The time of diagnosis, the length of stay and the hospital charges were compared between the two groups. T test and χ2 test were used for statistical analyses. Results: One hundred and nineteen of the cases were males and 20 were females. The age of onset was 4 months (8 d to 14 years), and 103 cases (74.1%) had onset before 1 year of age. The age at diagnosis was 1.8 years (21 d to 14.7 years), and the time of diagnosis delay was 1 year (7 d to 13.7 years). One hundred and thirty-five cases (97.1%) had pulmonary infection as the main reason for hospitalization, of whom 76 cases (56.3%) had positive pulmonary etiology. One hundred and thirty-six patients (97.8%) were referred cases, of whom 5 were suspected of CGD before referral, and the misdiagnosis rate was as high as 96.3% (131/136). Eight early clues for diagnosis were found, the frequency from high to low, large bacillus Callmette-Guer scar in 99 cases (70.5%), left axillary lymphadenopathy or calcification in 73 cases (52.5%), skin or other lymph node infections in 58 cases (41.7%), skin scars in 50 cases (36.0%), multiple lung nodules in 42 cases (30.2%), perianal abscess in 35 cases (25.2%), pulmonary Aspergillus infection in 26 cases (18.7%) and pulmonary Burkholderia infection in 15 cases (10.8%). A total of 120 cases of CGD were diagnosed by respiratory burst test during hospitalization, including 55 cases diagnosed before 2015 and 65 cases diagnosed after 2015. After using these 8 early diagnosis clues, the cases diagnosed after 2015 had shorter time of diagnosis and the length of stay and lower hospitalization charge than cases diagnosed before 2014, and the difference was statistically significant ((25±7) vs. (10±5) d, (29±7) vs. (18±6) d, (3.7×104±1.2×104) vs. (3.2×104±1.2×104) Yuan, t=13.763, 9.262, 2.381, all P<0.05). Conclusions: Patients with CGD are younger at onset and the diagnosis is delayed. Pulmonary infections are the most common. Large BCG scar, left axillary lymphadenopathy or calcification, skin or other lymph node infections, skin scars, multiple lung nodules, perianal abscesses, pulmonary Aspergillus infection and Burkholderia infection can help early diagnosis of CGD.