[Comparative analysis of the consistency of anesthesia depth between anesthesia index and Narcotrend index in monitoring pediatric tonsillectomy/adenoidectomy surgery].

Objective: To analyze the consistency of the anesthesia index (AI) and Narcotrend index (NI) in monitoring the depth of anesthesia in pediatric tonsil/adenoidectomy. Methods: A total of 129 children who underwent elective tonsil/adenoidectomy at Xijing Hospital Affiliated to Air Force Medical University from July 2022 to October 2023 were prospectively enrolled. Both AI monitoring by ConView monitor and NI monitoring by Narcotrend monitor were conducted for children after they were admitted to the operating room, while Propofol-remifentanil combined with total intravenous anesthesia was used during the operation and the anesthetic dose was adjusted to maintain the NI value at 40-60. In addition, the AI and NI values were recorded at following time points: quiet eyes closing (T1), the beginning of induction (T2), loss of consciousness (T3), tracheal intubation (T4), the beginning of surgery (T5), during tonsil excision (T6), adenoidectomy (T7), the end of surgery (T8), consciousness recovery (T9) and tracheal extubation (T10). Bland-Altman consistency analysis was used to evaluate the consistency of the results of the two types of anesthesia depth monitoring, AI value and NI value. Receiver operator characteristic (ROC) curve and area under curve (AUC) were used to analyze the predictive efficacy of AI and NI values for the state of consciousness of children. The intraoperative awareness was followed up at 24 hours, 1 week and 1 month after surgery. Results: In 129 cases, there were 78 boys and 51 girls, with an average age of (7.2±3.2) years and an operation time of (72.8±14.0) min. No AI data were missing, but 13 NI data were missing, with a missing rate of 10.1% (13/129). At time points T1-T10, the AI values were 67.5±19.2 and the NI values were 67.2±19.2. Bland-Altman consistency analysis showed that the difference in value between AI and NI was 0.3 (95%CI:-0.1-0.6, P=0.120), with an out-of-consistency range of 4.0% (51/1 290). Before anesthesia induction, AI and NI values were maintained at a high level; with the beginning of anesthesia induction and the disappearance of the children's consciousness, both AI and NI values gradually decreased; after discontinuing the infusion of anesthetics, the values of AI and NI gradually increased, and the change trend of AI and NI in each stage of the perioperative period was consistent, and there was no significant difference between the two groups at each time point (all P>0.05). ROC curve analysis showed that the cut-off value for predicting the state of consciousness using AI was 72.5, with an AUC of 0.73 (95%CI: 0.70-0.75), and the cut-off value of NI was 79.5 and the AUC was 0.74 (95%CI: 0.72-0.77). There was no significant difference in AUC between the two indices (P=0.310). None of the children had intraoperative awareness. Conclusion: Both AI and NI can be used to monitor the depth of anesthesia in pediatric tonsil/adenoidectomy with high accuracy.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Antimicrobials discovery against Staphylococcus aureus by high throughput screening of drug library].

To develop antimicrobials against Staphylococcus aureus by high throughput screening of drug library. The type of this study is experimental research. The clinical isolates of S. aureus were collected from the sputum samples of respiratory inpatient department of the Third Xiangya Hospital of Central South University. The anti-planktonic cells growth inhibition activity of FDA-approved drugs library (including 1 573 molecules) was assessed by building a planktonic cells screening platform; The biofilm inhibitory effect of the FDA-approved drugs was detected by building a biofilm screening platform combined with crystal violet staining; Minimal inhibitory concentrations of the selected hits were determined by broth microdilution assay. Finally, the cytotoxicity of the selected hits was detected by CCK-8 assay. The results showed that 218 hits were exhibited effective growth inhibitory effects against S. aureus by setting the concentrations of the molecules in the FDA-approved library to 100 µmol/L. These selected molecules are mainly anti-infective drugs, accounting for 118 hits; Followed by anti-cancer drugs, anti-inflammatory/-immune drugs, neurological drugs, cardiovascular drugs, endocrine drugs, and metabolic disease drugs, which accounts for 40, 19, 12, 9, 8, and 3 hits; Other unclassified drugs accounts for 9 hits. The top 10 hits exhibiting anti-planktonic cells activity against S. aureus were mainly including antitumor drugs, followed by neurological drugs and unclassified drugs like vitamin K3 with the inhibition rate of 99.65%-100%. Similarly, the top 10 hits showing biofilm inhibitory effects against S. aureus were also mainly including antitumor drugs, followed by neurological drugs and anti-inflammatory/-immune drugs with the inhibition rate of 50.22%-92.95%. The minimal inhibitory concentration (MIC) of the 51 hits by second round screening was determined by micro-dilution assay, which mainly include the antitumor drugs, cardiovascular drugs, endocrine drugs, anti-inflammatory/-immune drugs, metabolic disease drugs, neurological drugs and other unclassified drugs accounted for 22, 5, 3, 9, 2, 5 and 5 hits, respectively, with the MICs of 1.56-50 µmol/L, 6.25-25 µmol/L, 6.25-25 µmol/L, 0.2-50 µmol/L, 25-50 µmol/L, 1.56-50 µmol/L and 0.1-12.5 µmol/L, respectively. In conclusion, the minimum inhibitory concentrations of small molecules screened through high-throughput assay are at the level of micromolar with strong drug development potential and high modifiability. The high effective anti-planktonic cells and anti-biofilm activity by these molecules are expected to provide new ideas for the development of new antimicrobials against S. aureus.

[Granulomatous disease with liver injury as the main manifestation].

Hepatic granuloma is a kind of disease caused by both infection or non-infection etiologies, and it is found in approximately 2% to 15% of liver biopsies. Some of which could be identified by the pathological morphology. This article reviews the common etiology, pathological manifestations, diagnosis, and differential diagnosis of hepatic granuloma, which is hopeful to improve clinicians' and pathologists' awareness.

[Preliminary analysis of neuroprotective effects of capillary fascia preservation recurrent laryngeal nerve anatomical method in right level â ¥ dissection].

Objective: To investigate the application and effect of capillary fascia preservation between the recurrent laryngeal nerve (RLN) and common carotid artery (fascia preservation method) in nerve protection when dissecting right level Ⅵ lymph nodes for patients with papillary thyroid carcinoma. Methods: A retrospective cohort study enrolling 195 patients with papillary thyroid carcinoma undergoing right level Ⅵ lymph node dissection in Beijing Tongren Hospital from March 2021 to August 2022 was carried out. The RLN was dissected by fascia preservation method in study group and by routine method in control group. The intraoperative electrical signal amplitude of the RLN, the number of dissected lymph nodes, and the postoperative complications were recorded and analyzed. Results: A total of 195 patients (study group: 94 cases, control group: 101 cases) were collected. There were 71 males and 124 females, with the median age of 32 (39, 51) years. In the study group, the total number of right level Ⅵ lymph nodes was significantly larger than the number of right Ⅵa level lymph nodes [8 (6, 11) vs 6 (4, 8), P<0.001]. There were no significant differences between the two groups in the number of level Ⅵa or level Ⅵb lymph nodes [Ⅵa: 6 (4, 8) vs 5 (3, 7), P=0.373; Ⅵb: 3 (1, 4) vs 2 (1, 4), P=0.337] and metastasis rate [Ⅵa: 51.1% (48/94) vs 52.5% (53/101), P=0.844; Ⅵb: 12.8% (12/94) vs 15.8% (16/101), P=0.541]. The ratio of electromyography (EMG) amplitude R2 in lower level Ⅵ and entry into larynx (grouped as>90%, 50%~90%,<50%) in the study group was significantly higher than that in the control group (P<0.001). No significant differences were detected between the two groups in temporary RLN paralysis [1.1% (1/94) vs 2.0% (2/101), P=1.000]. Conclusions: Fascia preservation method can decrease the stimulus and traction to RLN and preserve the capillary network serving RLN. It can thoroughly dissect lymph nodes and decrease the injury of RLN.

[Analysis of clinicopathological characteristics of non-alcoholic fatty liver disease].

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg2 combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.

[Efficacy and safety of daratumumab in patients with relapsed/refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) µmol/L, which was significantly higher than that of low dosage group [66 (51, 76) µmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.

[Correlation of VISTA and PD-L1 expression with the clinicopathological features and prognosis in triple-negative breast cancer].

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8+T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.

[Research progress on the relationship between intestinal flora and colorectal cancer].

In recent years, the incidence of colorectal cancer has been increasing. Various evidences show that the change of intestinal flora is related with the progress of colorectal cancer. Intestinal opportunistic pathogens can promote the development of colorectal cancer, while probiotics can inhibit colorectal cancer. Changes in intestinal flora affect chemotherapy, surgery and other treatments. At the same time, intestinal flora has potential application in the treatment and diagnosis of colorectal cancer. This article reviews the recent advances in the relationship between intestinal flora and colorectal cancer.

[Clinical characteristics and prognosis of lymphoma-associated hemophagocytic syndrome].

Subjective To investigate clinical characteristics, treatment, and prognosis of lymphoma-associated hemophagocytic syndrome (LAHS) patients. Methods: The clinical data of patients diagnosed with LAHS from January 2010 to October 2021 in West China Hospital were retrospectively analyzed. Clinical characteristics, treatment, overall response rate (ORR), and overall survival (OS) were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of all 94 patients included, 59 were male and 35 were female. The age at hemophagocytic lymphohistiocytosis (HLH) diagnosis was (40.5±17.3) years. Seventy-four cases were T/NK cell lymphoma; 15 were B cell lymphoma; 5 were Hodgkin lymphoma. The age at HLH diagnosis of T/NK cell LAHS patients was (37.9±16.2) years, while that of B cell LAHS patients was (55.9±14.0) years. T/NK cell LAHS patients were significantly younger than B cell LAHS patients (P<0.001). Baseline fibrinogen of T/NK cell LAHS patients was 1.34 (0.86, 2.44) g/L, while that of B cell LAHS patients was 2.20 (1.75, 4.25) g/L. T/NK cell LAHS patients showed significantly lower fibrinogen levels than B cell LAHS patients (P=0.008). Combined treatment of anti-HLH and anti-lymphoma treatment was conducted in 35 patients; anti-HLH treatment was conducted in 31 patients; anti-lymphoma treatment was conducted in 8 patients; glucocorticoid treatment was conducted in 7 patients. ORR was 49.4%, and the median OS was 61 days for overall patients. Patients who received anti-HLH treatment and turned to anti-lymphoma treatment early displayed the best ORR and OS, significantly higher than those of anti-HLH patients (69.0 vs 38.7%, P=0.019, and 192.0 vs 24.5 days, P=0.028, respectively), which were also insignificantly higher than those of anti-lymphoma patients. Extranodal NK/T-cell lymphoma or aggressive natural killer cell leukemia was the risk factor of LAHS prognosis (HR=0.113, 95%CI: 0.018-0.728, P=0.022). Conclusions: Prognosis of LAHS patients is poor. Anti-lymphoma treatment should be initiated as soon as HLH is rapidly controlled.