1.Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells.
Rongrong CHEN ; Chunxiang JIN ; Kai LIU ; Mengyu ZHAO ; Tingting YANG ; Mingming ZHANG ; Pingnan XIAO ; Jingjing FENG ; Ruimin HONG ; Shan FU ; Jiazhen CUI ; Simao HUANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Chinese Medical Journal 2024;138(19):2481-2490
BACKGROUND:
B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.
METHODS:
Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.
RESULTS:
In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS.
CONCLUSION:
Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.
REGISTERATION
Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).
2.Characteristics of preliminary clinical diagnosis and treatment for gastritis cystica profunda accompanied with neoplastic lesions
Mo LIU ; Rui CHENG ; Simao LIU ; Qiaozhi ZHOU ; Yanhua ZHOU ; Ye ZONG ; Bing YUE ; Peng LI ; Shutian ZHANG
Chinese Journal of Digestive Endoscopy 2023;40(6):431-436
Objective:To investigate the clinical features, characteristics under white-light endoscopy and endoscopic ultrasonography, and treatment strategies of gastritis cystica profunda (GCP) accompanied with or without neoplastic lesions.Methods:Clinical data of 35 patients, who were pathologically diagnosed as having GCP after endoscopic or surgical resection in Beijing Friendship Hospital, Capital Medical University from January 2015 to February 2021, were retrospectively collected, including 27 patients with neoplastic lesions. The demographic information, clinical manifestations, endoscopic features, treatment methods, and pathological results of GCP were summarized.Results:Thirty-five patients with GCP were 68.26±8.08 years old, and mostly male (80.00%, 28/35). The most common symptom was upper abdominal pain, accounting for 31.43% (11/35), and 25.71% (9/35) had no symptoms. Other symptoms included acid reflux, heartburn, abdominal distension, anemia, and choking sensation after eating. The most common site of GCP was cardia (51.43%, 18/35), and the main endoscopic manifestations of GCP were flat mucosal lesions (68.57%, 24/35), mainly 0-Ⅱa and 0-Ⅱa+Ⅱc type lesions, accounting for 66.67% (16/24). The second common endoscopic manifestation was polypoid eminence (20.00%, 7/35). Endoscopic ultrasonography was performed in 15 patients, with main manifestations of uniform hypoechoic with or without cystic echo (73.33%, 11/15). Among the GCP cases, 33 patients received endoscopic resection, and 2 received surgical treatment. The treatment processes were all successfully completed, and en-bloc resection was accomplished for all lesions receiving endoscopy, with the mean endoscopic operation time of 86.13 min. One patient suffered postoperative delayed bleeding after ESD which was stopped by endoscopic hemostasis. Final pathological results showed that the proportion of GCP complicated with neoplastic lesions was 77.14% (27/35), 68.57% (24/35) with early gastric cancer or precursor. Twenty-three cases achieved R0 resection. One case showed positive basal resection margin and vascular invasion, and recurrence happened in situ at the 5th month of follow-up, surgical resection was then performed. The endoscopic complete resection rate was 95.83% (23/24).Conclusion:GCP usually occurs in middle-aged and elderly male, often located in cardia, manifested mainly as flat mucosal lesions and polypoid changes. Endoscopic ultrasonography shows a high diagnostic value for GCP, and endoscopic treatment is safe and effective minimally invasive treatment for GCP.
3.Effects of PNF Training on Functional Recovery of Sports Rotator Cuff Injury
Junji CHEN ; Tianxu GAO ; Xiaolong LIU ; Simao XU
Journal of Medical Biomechanics 2022;37(1):E174-E179
Objective To explore the effect of proprioceptive neuromuscular facilitation (PNF) rehabilitation training on functional recovery of athletic rotator cuff injury. Methods Twenty-two college students with athletic rotator cuff injuries were stratified according to their gender and randomly divided into resistance band + passive joint range of motion (ROM) training group (control group) and PNF training group (experimental group). The visual analog scale (VAS) was used to evaluate subjective pain intensity of the shoulder joint. Pain positive rate for each manipulation test of rotator cuff injury was observed, and active ROM and muscle strength of the shoulder joint were measured. Improved UCLA shoulder joint score was used to evaluate comprehensive function of the shoulder joint. Results After training, VAS scores and pain positive rate in two groups were lower than those before training, and VAS scores and pain positive rate in experimental group were lower than those in control group. Muscle strength, active ROM in all directions and improved UCLA score of the shoulder joint in two groups were also higher than those before training, and the internal rotation muscle strength, the internal rotation and external rotation active ROM, improved UCLA score of the shoulder joint in experimental group were higher than those in control group. Conclusions PNF rehabilitation training can reduce the pain of athletic rotator cuff injury, improve the active ROM, muscle strength and UCLA shoulder joint score. The function recovery effect of PNF training is better than that of resistance band + passive ROM training.
4.Clinical significance of ineffective esophageal motility in non-erosive acid reflux diseases
Simao LIU ; Wenyan LI ; Rui CHENG ; Fandong MENG
Chinese Journal of Digestive Endoscopy 2022;39(8):650-654
Objective:To investigate the role of ineffective esophageal motility (IEM) in non-erosive acid reflux related diseases, and the influence of the fourth edition Chicago classification (CC v4.0) on the diagnosis of IEM.Methods:From January 2018 to January 2020, 63 patients with acid reflux related symptoms who underwent gastroscopy and showed no abnormal changes in esophageal mucosa or structure, and underwent high resolution esophageal manometry (HRM) and 24-hour esophageal pH monitoring in the Department of Gastroenterology of Beijing Friendship Hospital were included in the case-control study. According to the HRM results, the third edition Chicago classification standard (CC v3.0) and CC v4.0 were used to divided patients into IEM group and normal dynamic group. The HRM results, 24-hour esophageal pH monitoring results and final diagnosis of the two groups under the two editions of Chicago classification standard were mainly compared and analyzed.Results:Among the 63 patients, there were 14 cases of non-erosive gastroesophageal reflux disease (NERD), 19 cases of reflux hypersensitivity (RH), and 30 cases of functional heartburn (FH). When using CC v3.0, there were 20 cases in the IEM group, including 9 cases of NERD, 5 cases of RH and 6 cases of FH, and 43 cases in the normal dynamic group, including 5 cases of NERD, 14 cases of RH and 24 cases of FH. When using CC v4.0, there were 16 cases in the IEM group, including 7 cases of NERD, 4 cases of RH and 5 cases of FH, and 47 cases in the normal dynamic group, including 7 cases of NERD, 15 cases of RH and 25 cases of FH. When using CC v3.0, compared with the normal dynamic group, the acid exposure time (AET) of the IEM group was significantly higher [3.45 (1.55, 6.40)% VS 1.20 (0.40, 2.30)%, Z=-2.940, P=0.003], the DeMeester score was also significantly higher [13.8 (5.8, 21.4) VS 5.3 (2.9, 10.0), Z=-2.851, P=0.004], the lower esophageal sphincter pressure (LESP) [10.15 (7.52, 13.65) mmHg (1 mmHg=0.133 kPa) VS 15.40 (11.20, 21.60) mmHg, Z=-3.241, P=0.001], 4-second integrated relaxation pressure (4sIRP) (3.79±0.57 mmHg VS 6.05±0.50 mmHg, t=2.727, P=0.008), and distal contraction integral (DCI) [334.65 (208.25, 438.92) mmHg·s·cm VS 1 258.70 (919.00, 1 750.10) mmHg·s·cm, Z=-6.305, P<0.001] were significantly lower than those of the normal dynamic group. When using CC v4.0, AET and Demeester scores in the IEM group were also significantly higher than those in the normal dynamic group (both P<0.05), and LESP, 4sIRP and DCI were also significantly lower than those in the normal dynamic group (all P<0.05). In addition, upper esophageal sphincter pressure was significantly lower than that in normal dynamic group [34.60 (21.50, 48.05) mmHg VS 49.67 (36.75, 61.10) mmHg, Z=-2.140, P=0.032]. Conclusion:IEM is associated with impaired anti-reflux barrier function and esophageal acid exposure in patients with non-erosive acid reflux related diseases. Compared with CC v3.0, CC v4.0 can reduce the heterogeneity of IEM patients to some extent.
5.Effects of peroral endoscopic myotomy on esophageal motility in patients with achalasia
Simao LIU ; Fandong MENG ; Wenyan LI
Chinese Journal of Digestive Endoscopy 2020;37(2):115-120
Objective:To evaluate the effects of peroral endoscopic myotomy (POEM) on esophageal motility in patients with achalasia(AC) after POEM.Methods:Demographics, clinical and manometric data, and outcomes were collected from the medical records of patients who received POEM as the primary therapy for AC in Beijing Friendship Hospital from January 2012 to June 2016. The rate of treatment success and change in esophageal dynamics before and after treatment were compared in different types of AC.Results:At 6 months′ follow-up of POEM, the symptom remission rate of AC patients with type Ⅰ, type Ⅱ, and type Ⅲ was 100.0% (13/13), 95.5% (42/44) and 90.1% (10/11), respectively. Within 6 months after POEM, lower esophageal sphincter resting pressure [10.5 (6.9, 15.8) mmHg VS 24.6 (18.3, 35.1) mmHg, 1 mmHg=0.133 kPa], 4 s integrated relaxation pressure [6.0 (3.7, 8.8) mmHg VS 21.8 (15.3, 28.0) mmHg], upper esophageal sphincter (UES)resting pressure [43.4 (33.7, 57.3) mmHg VS 45.3 (33.2, 71.1) mmHg] and UES residual pressure [1.5 (0.0, 4.6) mmHg VS 3.9 (1.1, 6.9) mmHg] were significantly improved compared with those of pre-operation (all P<0.05). At 6 months after POEM, esophageal dilatation diameter (3.0±0.7 cm VS 3.9±1.1 cm) and Eckardt scores [1 (0, 2) VS 6 (5, 8)] were also significantly improved compared with those of pre-operation (all P<0.001). After POEM, the esophageal body peristalsis did not recover in type Ⅰ AC patients. Four patients (9.1%, 4/44) of type Ⅱ AC recovered weak peristalsis or premature contraction, and 10 patients (90.9%, 10/11) of type Ⅲ AC recovered with more normal peristaltic wave, and the rate of pre-systolic contraction or weak peristalsis increased. Conclusion:POEM can improve the esophagogastric junction outflow tract obstruction and change the esophageal body motility.After POEM, part patients have recovery of esophageal body motility, which is most obvious in type Ⅲ AC, followed by type Ⅱ, and type Ⅰ AC patients have no significant change.
6.The clinical detection significance of serum miR-137 in central precocious puberty girls
Jiayan TANG ; Juan HUANG ; Lianhong HUANG ; Li ZHANG ; Yuling LIU ; Simao FU
The Journal of Practical Medicine 2016;32(15):2500-2503
Objective To investigate the clinical significance of testing serum kisspeptin in central precocious puberty (CPP) girls. Methods Sixty eight CPP girls and 68 healthy girls was studied from December 2012 to December 2014. HEK293 cells were cultured. Luciferase reporter assay was performed to verify the binding of miR-137 to the 3′UTR of KISS1. Serum miR-137 level was levaluated by qRT-PCR. Level of serum luteinizing hormone , prolactin , follicle stimulating hormone , thyrotropin , free thyroxine and estradiol was evaluated by chemi-luminescence immunoassay. The level of serum kisspeptin was detected by ELISA. Results MiR-137 was confirmed to bind to the 3′UTR of KISS1. The level of serum miR-137 was downregulated and kisspeptin was enhanced in CPP girls. The expression of miR-137 and kisspeptin was negatively correlated. Serum miR-137 level was negatively related to bone age and bone age advancement. According to the results of GnRH stimulating test, serum miR-137 was related to peak LH and peak/basal LH ratio. Conclusions MiR-137 could bind to the 3′UTR of KISS1. MiR-137 may be a potential biomarker for CPP assisted diagnosis.
7.Clinical and prognostic analysis of 27 pediatric patients with bronchiectasis caused by Mycoplasma pneumonia and Chlamydia pneumonia
Li ZHANG ; Tao ZHOU ; Simao FU ; Yuling LIU
Journal of Clinical Pediatrics 2015;(6):567-570
Objective To explore the clinical characteristics, treatment and prognosis of pediatric patients with bronchiec-tasis caused by Mycoplasma pneumonia (MP) and Chlamydia pneumonia (CP). Methods The clinical data from 27 MP and CP pneumonia pediatric patients with bronchiectasis suggested by the high resolution CT were retrospectively analyzed. Results The morbility rate of bronchiectasis caused by MP and CP pneumonia is 0.56%. The mean age of these patients was 75.4 ± 52.7 months. Among them, 27 cases (100%) had cough, 19 cases (70.4%) had fever, 10 cases (37%) had respiratory distress and 20 cases had lung auscultation. Sixteen cases were MP-IgM positive, 5 cases (18.5%) were CP-IgM positive and 6 cases (22.2%) were positive of both. Eight cases were combined with other pathogens infections, in which 6 cases were bacterial infections. The imaging ifndings showed diffuse bronchiectasis in 13 cases (48.1%) and local bronchiectasis in14 cases (51.9%). The bronchoscopy found endothelium in-lfammation, mucosal swelling, partial erosion and follicular hyperplasia in 16 cases (66.7%), the formation of short column sputum bolt in 5 cases (20.8%), in which 1 case had plastic bronchitis. All patients were treated with macrolides antibiotics, 10 cases (37%) combined with methylprednisolone, 3 cases (11.1%) combined with immunoglobulin and 20 cases (74%) combined with other anti-biotics. The average length of hospitalization was 12±4.3 days. The bronchiectasis sign disappeared within 4 months in 23 cases (92%). Two cases (8%) still had bronchiectasis after 9 to 15 months, with the recurrent pneumonia. Conclusions MP and CP pneumonia can lead to acute bronchiectasis. Most of patients are recoverable with effective treatment.
8.Analysis of disease spectrum in Epstein-Barr virus infected children in Zhongshan
Wei REN ; Xiaoling LONG ; Yuling LIU ; Simao FU
Journal of Clinical Pediatrics 2015;(2):164-166
Objective To study the epidemic characteristics and disease spectrum of Epstein-Barr virus (EBV) infected children in Zhongshan region, Guangdong province. Methods Clinical data from the children with positive EBV-DNA detected by real-time lfuorescent quantitative PCR between 2011 and 2013 was retrospectively analyzed. Results A total of 409 cases were detected with EBV-DNA positive from 3402 cases, with a total positive rate 12%, and the positive rate is 8.1%in 2011, 10.4% in 2012, 19.5% in 2013, there were significant differences among positive rate (χ2=6804.00, P<0.05). There was no statistically signiifcant difference in the positive rate of EBV-DNA between different gender (χ2=0.239, P>0.05) and different age groups (χ2=136.96, P<0.05). The positive rate of pre-school group is the highest. EBV infection can cause multiple system diseases. The most common disease caused by EBV infection was infectious mononucleosis (61.6%), followed by respiratory tract infection (26.7%), neck lymphadenitis (3.4%), idiopathic thrombocytopenic purpura (2.4%), etc. Among the 409 cases of EBV infection, the concurrent other pathogen speciifc IgM positive cases as MP-IgM positive (n=79), CP-IgM positive (n=47), Parvovirus B19-IgM positive (n=20), HSV-IgM positive (n=11), CMV-IgM positive (n=10), and RV-IgM positive (n=4) were found. Conclusions Infectious mononucleosis is the leading disease in children infected by EBV in Zhongshan region, the annual positive rate is increasing. Multiple pathogen speciifc IgM may be detected positive in children with EBV infection, which should be interpreted in combination with clinical status.
9.Clinical application of the nutritional risk screening and nutrition assessment in hospitalized children
Bingjie HE ; Yan LIAO ; Yuling LIU ; Xiaoling LONG ; Xiaoli WEN ; Simao FU
Chinese Journal of Applied Clinical Pediatrics 2014;29(19):1467-1470
Objective To investigate hospitalized children's nutritional risk and malnutrition occurrence,and to provide clinical basis for nutrition support.Methods Nutritional risk screening tool STRONGkids was applied to 651 cases of hospitalized children with nutritional risk screening,and through physical measurement to assess children' s nutritional status,at the same time during the patient's diagnosis,the length of time data for analysis was recorded.Results Of 651 cases of hospitalized children,7.07% (46 cases) were of highly nutritional risk,80.95% (527 cases) with moderate nutrition risk,and 11.98% (78 cases) were of low nutrition risk.Malnutrition rate was 22.58%,moderate malnutrition in 111 cases (17.05%),severe malnutrition in 36 cases (5.53%).The first three high risk diseases were congenital heart disease,chronic liver disease and chronic kidney disease(x2 =21.43,P <0.01).According to the result of nutrition evaluation concluded with congenital heart disease,chronic kidney disease occurred with severe malnutrition was far higher than other diseases(x2 =16.53,P < 0.05).Children with highly nutritional risk were more likely to have weight loss than the children with relatively low nutritional risk (P < 0.05),and their length of hospital stay were obviously longer than the children with low or moderate nutritional risk (P < 0.05).Conclusions The hospitalized children have high incidence of malnutrition,and different nutritional risks lead to different clinical outcomes.STRONGkids score method helps to evaluate nutritional risk in hospitalized children and detect malnutrition and potential deterioration,which is conducive to early comprehensive nutritional assessment and proper nutritional treatment,thus to improve their clinical outcomes.
10.Etiology and clinical characteristics of infectious mononucleosis-like syn-drome
Shengping XIAO ; Simao FU ; Yuling LIU ; Guilan WANG ; Xiaohong HUANG
Chinese Journal of Infection Control 2014;(7):408-410
Objective To analyze the etiology and clinical characteristics of infectious mononucleosis-like syndrome (IMLS).Methods Eighty-seven children with IMLS in a hospital from January 2006 to September 2013 were per-formed pathogenic detection,then clinical features were summarized and analyzed.Results The top 5 pathogens in IMLS were Mycoplasma pneumoniae (MP,n=20 ),cytomegalovirus (CMV,n=13),simplex herpes virus(HSV, n=11),Chlamydia (CP,n=11),and parvovirus B19 (Hpv B19,n=9 ),clinical manifestations of all kinds of dis-eases were similar,but the occurrence rates were slightly different.MP infection were mainly fever,hepatospleno-megaly,and lymphadenopathy,and most were associated with respiratory complications(including laryngitis,bron-chitis,and pneumonia),CMV infection were also showed fever and hepatosplenomegaly,but the latter was more ob-vious;rubella patients didn’t appear skin rash,but the other symptoms were obvious.Conclusion Etiologies of in-fectious mononucleosis-like syndrome are varied,MP infection is most common,the next is CMV.Pathogens should be ascertained to provide theoretical basis of treatment.

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