[Progress in application of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease].

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.

[Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement].

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma].

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

A study on serum pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG) levels in patients with acromegaly.

PURPOSE: Acromegaly caused by growth hormone cell adenoma is commonly associated with abnormal glucolipid metabolism, which may result from changes in adipocytokine secretion. This study aims to investigate serum adipokine levels, including pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG), in acromegalic patients and the correlation between the levels of these three adipokines and GH levels and glucolipid metabolism indices. METHODS: Sixty-eight acromegalic patients and 121 controls were included, and their clinical data were recorded from electronic medical record system. Serum PNT, furin and ZAG levels were measured by ELISA. RESULTS: Serum PNT levels in acromegalic patients were significantly higher than controls (66.60 ± 12.36 vs. 46.68 ± 20.54 pg/ml, P < 0.001), and acromegaly was an independent influencing factor of PNT levels (P < 0.001). Moreover, subjects with the highest tertile of PNT levels had a close correlation with acromegaly (OR = 22.200, 95% CI 7.156 ~ 68.875, P < 0.001), even in Model 1 adjusted for gender and age and Model 2 adjusted for gender, age and BMI. Additionally, serum PNT levels were positively correlated with BMI (r = 0.220, P = 0.002) and triglycerides (TGs, r = 0.295, P < 0.001), and TGs were an independent influencing factor of serum PNT levels in acromegalic subjects (P < 0.001). Furthermore, serum PNT levels in obese acromegalic patients were significantly higher than those with normal BMI (P < 0.05). However, serum furin levels were lower in acromegalic patients than controls (0.184 ± 0.036 vs. 0.204 ± 0.061 ng/ml, P < 0.001). CONCLUSION: This study is the first to demonstrate that acromegalic patients have increased serum PNT levels. Moreover, serum PNT plays a potential role in abnormal lipid metabolism of acromegalic patients.

Bone microarchitecture impairment in prolactinoma patients assessed by HR-pQCT.

PURPOSE: Prolactinoma may reduce bone mineral density (BMD) and increase fracture risk, but its influence on bone microarchitecture remains to be elucidated. The purpose of this study is to evaluate bone microarchitecture parameters by high-resolution peripheral quantitative computed tomography (HR-pQCT) in prolactinoma patients. METHODS: 31 prolactinoma patients and 62 age- and sex-matched healthy controls in our center were included, and HR-pQCT was used to evaluate their bone microarchitecture at the radius and tibia. Z-scores for bone microarchitecture parameters were calculated based on previously published reference. RESULTS: After adjusting for height and weight, prolactinoma patients had lower trabecular (- 0.011 mm, p = 0.005) and cortical thickness (- 0.116 mm, p = 0.008) and cortical area (- 6.0 mm2, p = 0.013) at radius, as well as lower trabecular (- 0.014 mm, p = 0.008) and cortical (- 0.122 mm, p = 0.022) thickness at tibia compared with the controls. Patients with higher prolactin level had more severe bone microarchitecture impairments. After adjusting for prolactin level and age, male patients had lower trabecular volumetric BMD (vBMD), trabecular number, trabecular thickness, and cortical porosity at radius, as well as lower trabecular vBMD, trabecular bone volume fraction, trabecular number, and cortical area, and higher trabecular separation at tibia compared with female patients. Z-score for radius vBMD was correlated with Z-score for areal BMD (aBMD) at lumbar and femoral neck, while Z-score for tibia vBMD was correlated with Z-score for lumbar aBMD, and some patients with vBMD Z-score below - 2.0 had aBMD Z-score within normal range. CONCLUSION: Peripheral bone microarchitecture was impaired in prolactinoma patients, especially in patients with higher prolactin level. We compared the bone microarchitecture of prolactinoma patients and healthy controls by high-resolution peripheral quantitative computed tomography (HR-pQCT), and found that many bone microarchitecture parameters were impaired among prolactinoma patients. Such impairment was more prominent among patients with higher prolactin level.

[Clinical observation and preliminary economic study of rush immunotherapy in patients with allergic rhinitis].

Objective: To observe the clinical efficacy, safety, compliance, and cost-effectiveness of rush immunotherapy (RIT) and conventional immunotherapy (CIT) in patients with allergic rhinitis (AR), so as to evaluate the clinical significance of CIT and preliminarily explore its economic value. Methods: A study was conducted on 72 AR patients who had received specific immunotherapy from Oct 2019 to Jun 2020 in the Department of Otorhinolaryngology, the First Affiliated Hospital of Chongqing Medical University, including 39 males and 33 females, aging 8 to 60 years. RIT or CIT was performed respectively according to the patients' wishes. There were 35 cases in the RIT group and 37 cases in the CIT group, all subjects were followed up for 1 year. Visual analysis scale (VAS) and effectiveness were used to evaluate the clinical efficacy. Systemic adverse reactions were used to assess safety. Failure rate was calculated to evaluate the compliance. The cost and cost-effectiveness ratio (CER) were conducted to evaluate the health economics preliminarily. Results: After half a year and one year's treatment, both RIT and CIT groups had significant clinical efficacy and RIT group had more significant clinical efficacy than CIT group at half a year (76.67% vs 46.67%, χ2=7.37, P=0.007). During the dose accumulation phase, there was no significant difference in the incidence of systemic adverse reactions between the two groups (8.57% vs 8.10%, χ2=0.05, P=0.943), while the drop-out rate in the RIT group was significantly lower than that in the CIT group (0 vs 13.51%, χ2=5.08, P=0.024). After one year, the costs in RIT group were significantly higher ((8 163.08±452.67) yuan vs (7 385.87±369.92) yuan, t=-2.78, P=0.009), while there was no statistical differences in CER between the two groups ((3 298.06±1 374.09) yuan/point vs (3 154.38±1 532.51) yuan/point, t=-0.36, P=0.418). Conclusions: Both RIT and CIT are beneficial for AR, and they have similar clinical efficacy, safety, and CER. RIT is more effective in the early stage, with higher patient compliance. Thus, RIT is worth promoting and exploring in clinic.

[Clinical features and prognosis of 166 cases of MYC/BCL2 double-expression diffuse large B-cell lymphoma].

Objective: To investigate the clinical features and prognosis of MYC/BCL2 double-expression diffuse large B-cell lymphoma (DEL) . Methods: The clinical data, including clinical characteristics, survival, and prognostic factors, of 166 patients with DEL treated at Peking University Third Hospital from January 2016 to December 2020 were retrospectively analyzed. Results: A total of 410 patients with diffuse large B-cell lymphoma were collected, including 166 cases (40.5%) of DEL. There were 82 males and 84 females with a median age of 63.5 (21-95) years at diagnosis. A total of 110 patients (66.3%) were aged over 60 years at initial diagnosis, 106 patients (106/163, 65.0%) had elevated lactate dehydrogenase (LDH) at diagnosis, 74 patients (74/160, 46.2%) had ß(2) microglobulin level over 3 mg/L at diagnosis, and 107 patients (107/163, 65.6%) had≥2 extranodal involvement. Sixty-five patients (65/166, 39.2%) had B symptoms, 131 patients (131/165, 79.4%) had stage Ⅲ and Ⅳ disease at initial diagnosis, 41 patients (41/161, 25.5%) had an International Prognostic Index (IPI) score of 0-2 at initial diagnosis, and 38 patients (38/161, 23.6%) had an IPI score of 3 at initial diagnosis. Eighty-two patients (82/161, 50.9%) had an IPI score of 4-5 at initial diagnosis. Nine (9/56, 16.1%) patients with DEL had MYD88 and CD79B mutations. Univariate analysis showed that age over 60 years (P=0.004) , increased ß(2) microglobulin level (P=0.002) , and high IPI score (P=0.003) were associated with poor overall survival (OS) . Increased ß(2) microglobulin level (P=0.031) , LDH level (P=0.017) , stage Ⅲ-Ⅳ (P=0.001) , high IPI score (P=0.013) , immunohistochemical p53 mutation (P=0.049) , and PIM1 mutation (P=0.039) were associated with poor progression-free survival (PFS) . Multivariate analysis showed that IPI score of 4-5 was an independent risk factor for the prognosis of DEL (HR=2.622, 95% CI 1.398-4.917, P=0.003) . Survival analysis showed that there was a significant difference in the PFS between patients with DEL and those without DEL (65.6% vs 75.1%, P=0.002) . However, there was no significant difference in the OS (81.8% vs 83.6%, P=0.226) . In patients with DEL, the overall response rate of R-EPOCH regimen was higher than that of RCHOP or RCHOP-like regimen (81.5% vs 63.4%, P=0.004) . Conclusion: DEL is a group of aggressive lymphomas with relatively poor PFS. The R-EPOCH regimen may improve the overall prognosis of patients.

Hsa-miR-34a-5p reverses multidrug resistance in gastric cancer cells by targeting the 3'-UTR of SIRT1 and inhibiting its expression.

Multidrug resistance (MDR) is a major obstacle to chemotherapy, which leads to ineffective chemotherapy, an important treatment strategy for gastric cancer (GC). The abnormality of microRNAs (miRNAs) is critical to the occurrence and progression of MDR in various tumors. In this study, hsa-miR-34a-5p was found to be decreased in multidrug resistant GC cells SGC-7901/5-Fluorouracil (SGC-7901/5-Fu) compared to the parental SGC-7901 cells. Overexpression of hsa-miR-34a-5p in SGC-7901/5-Fu cells promoted apoptosis and decreased migration and invasiveness after chemotherapy. In addition, overexpression of hsa-miR-34a-5p suppressed the growth of drug-resistant tumor in vivo. The mechanism of the effects of hsa-miR-34a-5p could include the regulation of the expression of Sirtuin 1 (SIRT1), P-glycoprotein (P-gp) or Multidrug resistance-related protein 1 (MRP1) through direct binding to the 3'-untranslated region (UTR) of SIRT1. Functional gain-and-loss experiments indicated that hsa-miR-34a-5p enhances the chemotherapy sensitivity of MDR GC cells by inhibiting SIRT1, P-gp and MRP1. In conclusion, hsa-miR-34a-5p can reverse the MDR of GC cells by inhibiting the expression of SIRT1, P-gp or MRP1.

[Progress in the traceability of tumor marker detection].

Tumor markers (TM) detection is of great significance in tumor screening, monitoring and treatment intervention, which puts forward higher requirements for its detection quality. TM traceability is very important in the process of reagent production and clinical laboratory testing, which can help improving the reliability and comparability of TM testing. Based on the current principles and classification system of metrology traceability in the world, this paper reviews the quality requirements of reference materials and reference measurement methods related to protein and nucleic acid of TM, as well as the problems existing in the international convention reference measurement procedure and traceability system of TM, so as to provide a new idea for the quality assurance work of TM detection.

[The correlation between the degree of anxiety/depression and the improvement of subjective and objective symptoms after functional endoscopic sinus surgery in chronic sinusitis].

Objective: To explore whether the improvement of subjective symptoms and objective grades after endoscopic sinus surgery in patients with chronic sinusitis (CRS) are related to the degree of preoperative anxiety or depression and to provide reference for improving the effects of clinical treatment. Methods: The clinical data of one hundred and sixty patients with CRS treated by endoscopic sinus surgery in the First Affiliated Hospital of Chongqing Medical University from April 2018 to August 2019 were collected prospectively. The visual analogue scale (VAS) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, Lund-Kennedy scores of nasal endoscopy and the Lund-Mackay scores of CT before and 6 months after surgery were used to analyse the correlation between the scores of anxiety or depression and the subjective and objective scores of patients before and after operation by grouping and layering. One hundred and one males (63.1%) and 59 females (36.9%) with an average age of 47.3 years (18-75 years) were included. Single-sample, independent or paired t-test, one-way ANOVA and rank-sum test were used for comparison and Pearson correlation analysis was used for the correlation between groups. Results: There was no statistical difference of anxiety or depression between different groups in terms of age, gender and course in the 160 effective patients (t values were -0.151, -0.487, -0.846, all P values>0.05; t values were -0.473, -1.302, -1.069, all P values>0.05). And the degree of preoperative anxiety or depression was positively correlated with the subjective scores, including overall discomfort, nasal obstruction, runny nose and olfactory decline (r values were 0.515, 0.606, 0.424, 0.306, all P values<0.01; r values were: 0.518, 0.584, 0.448, 0.308, all P values<0.01), but not significantly correlated with objective scores of Lund-Mackay and Lund-Kennedy (all P value>0.05). Moreover, as far as the symptoms of overall discomfort, nasal obstruction, headache and runny nose, the results of one-way ANOVA showed that the improvement of symptoms in patients with serious anxiety or depression was worse than that of the normal, mild and moderate patients (all P values<0.05). However, there was no significant difference in the scores of Lund-Kennedy 6 months after surgery between them (both P values>0.05). Conclusion: The state of anxiety or depression affects the improvement of symptoms after endoscopic sinus surgery for CRS patients. Compared with the patients with normal and mild to moderate anxiety or depression, the improvement of symptoms in patients with severe anxiety and depression is worse. It is necessary to evaluate the anxiety or depression of the patients with CRS who are going to undergo endoscopic sinus surgery.

[Application of the subjective and objective evaluation in functional rhinoplasty].

Objective: To explore the subjective and objective evaluation methods in functional rhinoplasty. Methods: Sixty-four patients who underwent rhinoplasty in the Department of Otorhinolaryngology, the First Affiliated Hospital of Chongqing Medical University were included in this study from January 2017 to October 2018. There were 32 males and 32 females, with the age ranging from 18 to 45 years old. Before and 6 months after operation, nasal ventilation function was evaluated by Visual Analogue Scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE), nasal acoustic reflex and nasal resistance. Satisfaction with nasal appearance was evaluated by VAS, Rhinoplasty Outcome Evaluation (ROE) and facial proportions evaluation. Psychological state was assessed by Emotional Balance Scale and Rosenberg Self-esteem Scale. Finally, the Pearson correlation analysis of patient satisfaction was performed. SPSS 23.0 software was used for statistical analysis. Results: Compared with pre-operation, nasal obstruction VAS, NOSE scores, total nasal resistance and difference ratio of nasal resistance showed significantly decline after surgery (1.62±0.85 vs 7.56±1.44, 22.62±3.54 vs 69.75±7.85, (0.16±0.08) Pa·s/ml vs (0.31±0.43) Pa·s/ml, 0.33±0.28 vs 0.71±0.32, all P<0.05). VAS of appearance and ROE scores showed an increase after surgery (11.20±3.66 vs 2.70±0.97, 17.80±2.71 vs 7.50±1.12, all P<0.05). The measurement of the external nasal subunits showed that the length of the dorsum of the nose, the angle of the face to the nose, the angle of the frontal and the angle of the alar of the nose were obviously reduced ((29.33±4.26) mm vs (33.61±5.24) mm, (135.11±3.81)° vs (139.91±6.30)°, (130.63±2.88)° vs (136.74±5.72)°, (99.71±4.02)° vs (106.27±5.60)°, all P<0.05). The scores of postoperative Emotional Balance Scale and Rosenberg Self-esteem Scale increased significantly (5.88±1.54 vs 4.31±1.85, 28.31±2.64 vs 22.13±2.77, all P<0.05). The Pearson correlation analysis showed that patients' satisfaction was positively correlated with subjective score of nasal ventilation (VAS, NOSE), subjective score of nasal appearance (VAS, ROE) and emotional balance scale, while negatively correlated with nasal resistance, and not correlated with the measurement of external nasal subunit. There was a significant positive correlation between the subjective score of nasal ventilation and the measurement of nasal resistance, but there was no significant correlation between the subjective score of nasal appearance and the measurement of external nasal subunit. Conclusion: The subjective and objective evaluation of nasal ventilation function, aesthetics of nasal appearance and psychological state can evaluate the effect of functional rhinoplasty effectively.

Relationship between the status of phospholipase A2 receptor and prognosis of idiopathic membranous nephropathy.

AIM: Serum levels of phospholipase A2 receptor antibody (PLA2R; SAb) and glomerular deposits of PLA2R antigen (GAg) have been detected in patients with idiopathic membranous nephropathy (IMN). However, the correlation between these immunologic factors and their associations with the status and prognosis of IMN remain uncertain. METHODS: Fifty-one patients with biopsy-proven IMN diagnosed between March of 2015 and December of 2016 were enrolled in this study. All the patients were followed until March of 2017.We used enzyme-linked immunosorbent assay and immunofluorescence to measure the SAb and GAg, respectively. RESULTS: The positive rate of GAg was significantly higher than SAb in patients with IMN (88.24 vs 66.77%, P = 0.017). Compared with SAb- patients, SAb+ patients had a higher baseline proteinuria (6.21 vs 3.40 g/24 h), lower serum albumin (22.49 ± 6.59 vs 29.09 ± 7.40 g/L) and poorer renal function (88.96 ± 21.17 vs 107.25 ± 20.04 mL/min per 1.73 m2 ), as well as a higher renal IgG4 level (P < 0.05). A comparison of SAb+/GAg+ and SAb-/GAg+ tissues yielded similar results (P < 0.01). Regarding prognosis, SAb- patients had a higher rate of complete remission after immunosuppressive treatment than SAb+ patients (P = 0.042). CONCLUSION: The disease status and prognosis correlated more closely with the SAb than with the GAg in our cohort of patients with IMN. Furthermore, SAb+ patients had more severe clinical symptoms and a worse prognosis, which was probably associated with increased IgG4 deposition.

[Application and influencing factors of endorectal ultrasound in T-stage restaging of rectal cancer following neoadjuvant therapy].

Objective: To evaluate the accuracy and influencing factors of T-stage restaging of rectal cancer following neoadjuvant therapy with endorectal ultrasonography (ERUS). Methods: In a retrospective study, endorectal ultrasound was performed in 86 patients with rectal cancer following neoadjuvant therapy. The imaging results were compared with postoperative pathological T-stage. Results: The accuracy of overall T-stage restaging with ERUS was 67.4% (58/86). Additionally, the accuracy of restaging in middle and high rectal cancer was higher, with an accuracy of 76.1%(35/46)and 100%(4/4) respectively. Univariate analysis showed that the location of tumors was an independent factor affecting the accuracy of ERUS(P=0.033). Conclusion: ERUS is an effective method to restage T-stage of rectal cancer following neoadjuvant therapy.

[Holistic concept of rhinoplasty].

In the past 20 years, nasal cavity plasty was operated by the otolaryngologists, while external rhinoplasty was usually implemented by the plastic surgeon respectively. The holistic concept is about the integrity, unity and connection of things and phenomena.Considering the structure and function of the external nose and the nasal cavity as a whole,we review the holistic concept in rhinoplasty and put forward the operation of holistic rhinoplasty, including the nasal cavity plasty and external rhinoplasty, correcting the structure problems of nasal cavity and the external nose deformity, and restoring its physiological and cosmetic functions at the same time.