[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.

[Application and innovation of bronchoscopic lung volume reduction with endobronchial valve].

Bronchoscopic lung volume reduction with endobronchial valve (BLVR-EBV) involves the placement of an endobronchial valve (EBV) in the emphysema area of patients with chronic obstructive pulmonary disease (COPD) via bronchoscopy, resulting in the collapse of the target lung lobe. This procedure has been shown to improve pulmonary function, quality of life, and activity endurance in COPD patients. Strict selection criteria and thorough preoperative evaluation are essential to ensure the success of BLVR-EBV. Due to its excellent postoperative performance, BLVR-EBV has been widely used in the treatment of patients with end-stage COPD, including those with conditions such as pulmonary tuberculosis cavities or those requiring surgical treatment. This paper provided a brief overview of the application and innovation of BLVR-EBV in patient assessment, perioperative management, and postoperative outcomes.

[Clinical application of flexible bronchoscopy in the treatment of airway foreign body].

Airway foreign body is the unintentional entry of objects into the larynx, trachea, or bronchi, causing airway obstruction, severe coughing, wheezing, breathing difficulties, or even asphyxiation. It is a common emergency condition in respiratory, critical care, emergency, otolaryngology, and pediatric departments, etc. With the popularization of flexible bronchoscopic techniques, endoscopic foreign body removal has been widely used in adults and children. The combined application of various instruments, such as alligator forceps, mesh baskets, balloons, and cryoprobes could safely and effectively remove foreign body. This article briefly described the treatment modalities for airway foreign body and summarized effective approaches using flexible bronchoscopy in its treatment.

[Clinical application and progress of airway stent in subglottic stenosis].

Laryngotracheal stenosis is caused by various reasons of laryngotracheal cartilage stent malformation, collapse or defect, laryngotracheal mucosa scar formation or submucosal tissue hyperplasia, eventually resulting in dyspnea. Subglottic stenosis refers to the airway stenosis from subglottic to the lower margin of the cricoid cartilage, which is a special type of laryngotracheal stenosis. The most common cause is iatrogenic injury, such as prolonged tracheal intubation and tracheotomy. Currently, the main treatments include surgical treatment, tracheostomy, endoscope-guided stent implantation and drug therapy. As for the patients who have dyspnea not suitable for surgery or in urgent need of preoperative transitional treatment, stent implantation guided by respiratory endoscopy has become an important treatment. In this paper, we reviewed 51 literatures on stent implantation of subglottic stenosis since 1994 retrieved from PubMed, CBM, CNIT, Wan-fang and VIP databases, focusing on the comparison of the efficacy, complications and prognosis of metal stent, hourglass-shaped DUMON stent, straight-type DUMON stent and Montgomery T tube and investigated the clinical application of endoscope-guided stent implantation in subglottic airway stenosis. Literature studies have shown that compared with DUMON silicone stents and metal stents, T tube has more significant advantages, higher treatment success rate and lower complication rate. Therefore, Montgomery T tube is more suitable for long-term treatment of patients with subglottic stenosis. With the improvement and update of new technology and materials, the vigorous development of new airway stents also provides a new stent treatment mode with better histocompatibility, fewer complications and customized options for the patients with subglottic stenosis.

[Effectiveness and safety of robotic assisted-bronchoscopy system in locating and removing spring coils placed in the peripheral lung of beagle dogs: a pilot study].

Objective: To evaluate the effectiveness and safety of the robotic assisted bronchoscope system for localizing and removing the spring coils that placed in the peripheral lung of beagle dogs. Methods: The study was conducted from June 18th to June 20th, 2021. Metallic lung coils were placed as the simulated lesions to the periphery of the lungs of two adult male beagle dogs using a bronchoscope under general anesthesia. The navigation path was planned by the navigation function that built in the robotic bronchoscope system. After training, the doctors operated the robotic bronchoscope system to locate and remove the coils from the lung. The navigation success rate, sampling success rate, position of the coil, navigation time, sampling time, and operation time were evaluated. The damage to the airway mucosa during the operation and the vital signs of the beagles during and post-operation were accessed. Chest computerized tomography (CT) was performed post-operation to detect if there were complications such as pneumothorax and bleeding. Results: A total of 12 spring coils were successfully inserted into the two beagles. All the navigation paths of the simulated lesions were successfully planned. The navigation success rate was 12/12. The navigation time was (43.9±19.8) seconds. The distance between the tip of the flexible endoscope arm and the target point measured by the navigation system was (6.93±2.15) mm. The locations of the simulated lesions were distributed in the 6th-8th generation of bronchi. The sampling success rate was 12/12. The sampling time was (42.4±11.3) seconds. There was no pneumothorax or mediastinal emphysema after the placement of the coil. The vital signs of the beagle dogs were stable throughout the operation, and no operation-related or postoperative complications occurred. Conclusions: The robotic bronchoscope system can be used to locate and remove the spring coils from the peripheral lung of beagle dogs, and the procedure is simple and safe. It suggests that the robotic bronchoscopy system has great clinical significance in the sampling and diagnosis of peripheral lung lesions.

[Anti-lung cancer effect of myeloid and plasmacytoid dendritic cell combined vaccines loaded with tumor cell lysates in vitro].

Objective: To investigate the feasibility of myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated Lewis lung cancer cell lysates for treatment of lung cancer in mice. Methods: Bone marrow cells were induced by the recombinant mouse fms-like tyrosine kinase receptor 3 ligand (rmFlt3-L) in vitro, myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were separated by magnetic beads. The mDC, pDC, and mDC∶pDC=1∶1 were stimulated with heat-treated Lewis lung cancer cell lysates, respectively. The effects of each group on stimulating of lymphocyte proliferation and inducing of T cell to kill tumor cells in vitro were compared. The alternations of the immunophenotypes of CD80, CD86, CD40 and major histocompatibility complex Ⅱ (MHC-Ⅱ) were detected by flow cytometry. The secretion of cytokines including interlukin-12 (IL-12), interlukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Results: The lymphocyte proliferation in mice stimulated with mDC+ pDC group loaded with heat-treated Lewis lung cancer cell lysates was 10.80±0.66, significantly higher than 8.63±0.65 of mDC group and 7.10±0.46 pDC group under the same culture conditions, respectively (P<0.05). When the ratio of effector cells: target cells (E∶T) was 10∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 31.68%±2.93%, significantly higher than 17.44%±0.97% of mDC group and 10.29%±1.33% of pDC group, respectively (P<0.05). When the ratio of E∶T was 20∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 54.77%±3.28%, significantly higher than 35.25%±1.51% of mDC group and 15.52%±0.73% of pDC group, respectively (P<0.05). When the ratio of E∶T was 40∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 73.01%±0.91%, significantly higher than 51.36%±0.58% of mDC group and 22.65%±1.28% of pDC group, respectively (P<0.05). With the rate of E∶T increased, the killing rate also increased. The mean fluorescence intensities of surface molecules including CD80, CD86, CD40 and MHC-Ⅱ of mDC: pDC=1 group pulsed with heat-treated Lewis lung cancer cell lysates were higher than those of mDC group and pDC group. The IL-6 cytokine concentrations of mDC+ pDC group, mDC group and pDC group loaded with heat-treated Lewis lung cancer cell lysates were (586.67±52.52) pg/ml, (323.33±67.14) pg/ml and (166.67±16.07) pg/ml, respectively. The concentrations of IL-12 in each group were (2 568.75±119.24) pg/ml, (2 156.25±120.55) pg/ml and (672.92±31.46) pg/ml, respectively. The concentrations of TNF-α in each group were (789.33±48.08) pg/ml, (584.89±116.49) pg/ml and (291.56±40.73) pg/ml, respectively. The concentrations of IL-6, IL-12 and TNF-α secreted by mDC+ pDC group were much higher than those of mDC group and pDC group under the same culture conditions (P<0.05). Conclusions: The mDCs and pDCs combined vaccines pulsed with heat-treated Lewis lung cancer cell lysates have synergistic effects on inducing of T lymphocyte proliferation and killing tumor cells in vitro. This synergistic anti-tumor effect is related with up-regulation of co-stimulatory molecules and increased secretion of cytokines.

[The efficacy and safety of transbronchial lung cryobiopsy in interstitial lung disease: a prospective study].

Objective: To evaluate the efficacy and safety of transbronchial lung cryobiopsy (TBCB) and conventional transbronchial lung biopsy (TBLB) in the diagnosis of interstitial lung diseases(ILD). Methods: A prospective, self-control study was conducted during January 2017 and April 2017 in First Affiliated Hospital of Guangzhou Medical University. A total of 25 patients [male 16, female 9; mean age (51±13) years, range 24 to 70 years] with inconclusive diagnosis of interstitial lung diseases were sequentially enrolled. In the study, TBCB (TBCB group) and TBLB (TBLB group) were performed successively under general anesthesia in all patients. The size of biopsy specimens, the duration of procedures, complications and pathological results were recorded. Gaussian distribution data were compared between 2 groups by using Student's t test, while abnormal distribution data were compared by using Wilcoxon rank sum test. The incidences of bleeding and pathologic diagnostic yield between the 2 groups were compared by using Pearson chi-square test. A P-value< 0.05 was assumed to be statistically significant. Results: The specimen sizes of TBCB group and TBLB group were (12.3+ 4.9) and (3.1+ 1.9) mm(2) respectively (t=-18.268, P=0.000). The duration of procedures was (7.8±3.2) and (5.4±2.1)min respectively (Z=-3.001, P=0.003). In TBCB group, the diagnostic yield was 72% (18/25), with valuable pathological results in 2 cases (8%), but in 5 cases (20%) it failed to provide valuable pathological results. In TBLB group, the diagnostic yield was 12% (3/25). There were no useful pathological results in other 22 cases. The difference in the rate of useful pathological results between TBCB group and TBLB group was significant (χ(2)=20.779, P=0.000). There was no pneumothorax or severe bleeding. The rate of mild to moderate bleeding in TBCB group and TBLB group was 47.2%(50/106) and 18.9%(20/106) (χ(2)=19.195, P=0.000) respectively. Conclusion: TBCB is superior to TBLB for lung biopsy as indicated by larger sample size, higher diagnostic yield and less complication. TBCB is valuable for the diagnosis of ILD.

[A retrospective study of the perioperative complications following whole lung lavage in the treatment of pulmonary alveolar proteinosis].

Objective: To evaluate the safety of the procedures of whole lung lavage(WLL) for pulmonary alveolar proteinosis(PAP) in perioperative period. Methods: In this retrospective study, we collected clinical data from 78 WLL procedures of PAP patients from January 2006 to June 2016 in Guangzhou Institute of Respiratory Disease. The causes of perioperative complications were analyzed. Results: Eighteen (23.07%) of the 78 procedures developed complications, including pleural effusion(n=4), pneumonia(n=4), cardiac failure(n=2), cardiac arrhythmia (n=2), pneumothorax(n=2), atelectasis(n=1), lung edema(n=1), laryngeal edema(n=1), pleural effusion and pneumonia(n=1). All complications were mild and easy to treat. Seventy-four procedures had successful extubation, but 4 procedures developed a prolonged time of extubation. Age, DSS, PaCO(2,)FEV(1,)lavage volume, lavage times and underlying diseases were not predictors for any complications(each P>0.05). High fluid recovering rate had a protective effect against the occurring of complications (Wald=7.672, OR<0.01, P<0.05). Conclusions: Whole lung lavage was a safe procedure in the treatment of PAP. Complications could recovery after proper therapy. The perioperative complications showed a correlation with low fluid recover rate. Operation under guideline was the key to avoid complications.

[Epidemiological trends for human schistosomiasis prevalence in Hubei Province from 2004 to 2018 based on Joinpoint regression analysis].

OBJECTIVE: To analyze the trends of human schistosomiasis prevalence in Hubei Province from 2004 to 2018, so as to provide the evidence for formulating the schistosomiasis elimination strategy in the province. METHODS: All data pertaining to human schistosomiasis prevalence in Hubei Province were collected from 2004 to 2018, and the trends for changes in seroprevalence, egg-positive rate and prevalence of human Schistosoma japonicum infection were analyzed using a Joinpoint regression model. RESULTS: Both of the numbers of residents seropositive and egg-positive for S. japonicum infections appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the prevalence of human S. japonicum infections reduced from 6.85% in 2004 to 0 in 2018. Joinpoint regression analysis showed that the prevalence of human S. japonicum infections appeared an overall tendency towards a reduction in Hubei Province from 2004 to 2018 [average annual percent change (AAPC) = -24.1%, P < 0.01], and the trends for the reduction were both significant during the period from 2004 to 2006 [annual percent change (APC) = -35.1%, P < 0.01] and from 2006 to 2018 (APC = -22.1%, P < 0.01). The prevalence of human S. japonicum infections appeared a tendency towards a decline in islet (AAPC = -25.1%, P < 0.01), inner embankment (AAPC = -26.4%, P < 0.01) and hilly subtypes of schistosomiasis-endemic areas (AAPC = -32.5%, P < 0.01) of Hubei Province from 2004 to 2018, and the prevalence all appeared a tendency towards a decline during the infection control stage (from 2004 to 2008), the transmission control stage (from 2009 to 2013) and the transmission interruption stage (from 2014 to 2018) (AAPC = -28.0%, -24.4% and -63.8%, all P values < 0.01). The seroprevalence of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = -14.5%, P < 0.01), and the trends for the reduction were both significant during the period from 2004 to 2012 (APC = -8.4%, P < 0.01) and from 2012 to 2018 (APC = -22.1%, P < 0.01). In addition, the egg-positive rate of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = -30.6%, P < 0.05), and the trend for the reduction was significant during the period from 2007 to 2014 (APC = -15.5%, P < 0.01). CONCLUSIONS: The prevalence of human schistosomiasis appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the islet and inner embankment subtypes of endemic areas are a high priority for schistosomiasis control during the stage moving towards elimination in Hubei Province.

[Establishment of an indicator system for schistosomiasis transmission risk assessment after transmission interruption in Hubei Province based on the Delphi method].

OBJECTIVE: To establish an indicator system for assessment of schistosomiasis transmission risk after transmission interruption in Hubei Province, so as to provide insights into the precise control of schistosomiasis. METHODS: The indicator system was preliminarily established based on data collection, literature review, expert interviews. Two rounds of expert consultation were performed. The indicator system was screened based on the importance, operability, sensitivity and comprehensive score of the indicators, and the weights of each indicator were calculated. The credibility of the Delphi method was evaluated by calculating the active coefficient of the experts, degree of expert authority and coordination levels of experts' opinions. RESULTS: An indicator system for assessment of schistosomiasis transmission risk was preliminarily established, including 3 primary indicators, 12 secondary indicators and 44 tertiary indicators. A Delphi consultation was performed among 17 experts participating in schistosomiasis control, management and research. Following two rounds of consultation, a risk assessment indicator system was finally constructed, including 3 primary indicators, 10 secondary indicators and 35 tertiary indicators. Among the primary indicators, the variable with the highest normalized weight was the current status of schistosomiasis (0.420 2), followed by social factors (0.397 3) and natural environments (0.182 5). Among the secondary indicators, those with high combined weights included risk monitoring (0.142 3), current snail status (0.140 1), and current prevalence of human and livestock infections (0.137 8). Among the tertiary indicators, those with high combined weights included the positive rate of wild feces (0.049 8), the prevalence of snail infections (0.047 4), and the area of snail habitats submerged by floods (0.046 8). During the two-round consultation, the active coefficients of the experts were 85.00% and 100.00%, the degree of expert authority was both 0.75 and greater, and the coordination levels of experts' opinions were 0.405 to 0.521 and 0.592 to 0.695 (all P values < 0.05). CONCLUSIONS: An indicator system for assessment of schistosomiasis transmission risk is successfully established after transmission interruption in Hubei Province based on the Delphi method, which provides insights into the identification of the schistosomiasis transmission risk and the targets for schistosomiasis control in Hubei Province.

[Survey of snail distribution in Four-lake Basin of Hubei Province].

OBJECTIVE: To investigate the distribution of Oncomelania snails in Four-Lake Basin of Hubei Province, so as to provide scientific evidence for the development of snail control interventions. METHODS: The snail distribution was surveyed by means of the retrospective study and cross-sectional survey in the Four-Lake Basin in Spring of 2016. The data pertaining to the endemic situation of schistosomiasis were collected and analyzed in the Four-Lake Basin from 2008 to 2018, and the associations of snail habitat areas with the prevalence of Schistosoma japonicum in humans and bovines were examined. RESULTS: There were 16 003 snail habitats in the 9 schistosomiasis-endemic counties (districts) in the Four-Lake Basin in 2016, covering an area of 246 million m2. The mean density of living snails was 0.622 5 snails/0.1 m2, which was relatively high in weed-type settings (0.688 0 snails/0.1 m2) and ditches (0.706 4 snails/0.1 m2). Type I (current snail habitats, 53.03%) and Ⅱ- Ⅳ (historical snail habitats, 46.97%) settings were predominant snail habitats. A big change was seen in snail habitats in dry farmland, marshland and paddy farmland, and environmental modification resulted in satisfactory snail control effectiveness. In addition, the area of snail habitats positively correlated with the changes in the prevalence of S. japonicum infections in humans (r = 0.842, P < 0.01) and livestock (r = 0.695, P < 0.01). CONCLUSIONS: The integrate strategy with an emphasis on the control of the source of S. japonicum infections results in remarkable snail control effectiveness in the Four-Lake Basin; however, there is a risk of re-emerging snail habitats.

Studies on the efficacy and persistence of the microbial agent bacillus sphaericus against larvae of culex pipiens pallens.

This paper evaluates the efficacy of the bacterial larvicide bacillus sphaericus strains BS-10 and C3-41, which are isolated in China, as well as BS2362 against larvae of Culex pipiens pallens in laboratory and under field conditions. The results indicate that C3-41 has the highest toxicity with LC50 at 0.0057 ppm and the bacterial formulations are more effective in light polluted water than in heavy polluted one, but the action of B. sphaericus could persist longer in more polluted water.

[Optimum number of mixed peripheral blood samples by membrane filtration technique for mass blood survey of filariasis].

The membrane filtration technique has been used widely in the evaluation of effect of control and survey of filariasis. The present study was made to explore an optimum number of mixed peripheral blood samples and a mathematical model of work load for this method in surveying filariasis. By analysing the correlation between the microfilaremia rate and the optimum number of mixed peripheral blood samples and applying the theory of Binomial Distribution or Poisson Distribution, the authors reckoned a table for estimating the number of filariasis cases in villages with different microfilarial rates and different population as well as the optimum number of mixed peripheral blood samples.

E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia.

A 5-year-old boy who initially presented with ALL and relapsed 4 months later with AML was found to have an add(19) in the leukemia cells. FISH revealed that the add(19) was really a cryptic t(l2;l9)(p13.3;p13.3) interrupting E2A (TCF3). Nucleotide sequences of cloned genomic fragments with the E2A rearrangements revealed that the der(12) contained E2A joined to an intron of the NOLI (p120) gene. Reverse transcriptase (RT)-PCR of patient lymphoblast RNA showed expression of in-frame fusion cDNAs consisting of most of NOL1 fused to the 3' portion of E2A that encoded part of the second transcriptional activation domain and the DNA binding and protein dimerization motifs. The reciprocal der(19) E2A genomic rearrangements included 5' regions of E2A joined to an intron of the ZNF384 (NMP4, CIZ) gene, located approximately 450 kb centromeric to NOL1 on chromosome 12. RT-PCR showed expression of in-frame E2A-ZNF384 fusion cDNAs. To our knowledge, this is the second report of a chromosome translocation in leukemia resulting in two different gene fusions. This is the first report of expression of E2A fusion protein that includes the DNA binding and protein dimerization domains due to a more proximal break in E2A compared to those described previously.