[L-DEP regimen salvage therapy for refractory primary hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus infection in 4 children].

Objective: To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children. Methods: In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children's hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed. Results: Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT. Conclusion: L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

[Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis].

Objective: To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH). Methods: This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children's hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate. Results: Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive. Conclusions: For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].

Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS).

Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database. INTRODUCTION: We investigated 33,480(0.14%) ABL-related adverse events (AEs) through data mining of Food and Drug Administration Adverse Event Reporting System (FAERS) retrospectively. METHODS: Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to quantify the signals of ABL-related AEs from 2017Quarter2 to 2022.Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test. RESULTS: We collected 8,470,497 reports from the FAERS database, including 11,487 reports defined ABL as the primary suspected (PS) drug. Additionally, 36.16% of the reports were submitted by healthcare professionals (n=4154), compared to 62.26% reported by consumers (n=7140). A total 99 signals simultaneously conforming to four algorithms were detected, among which, 35 signals were identified as unexpected signals. Such as growing pains (n=13), waist circumference increased (n=21), sensory disturbance (n=103), tinnitus (n=65), visual acuity reduced (n=54), blood alkaline phosphatase increased (n=61), and hair growth abnormal (n=13). Patient age (p < 0.001) might be associated with an increased risk of AEs severity. The most common timeframe for AE occurrence was 0-7 days. CONCLUSION: Our study provided a deeper and broader understanding of abaloparatide's safety profiles, which would help healthcare professionals to mitigate the risk of AEs in clinical practice, a low number of unexpected AEs supporting ongoing additional pharmacovigilance.

Research and application of a new multilevel fuzzy comprehensive evaluation method for cold stress in dairy cows.

Effective and comprehensive evaluation of cold stress is critical for healthy dairy cow breeding in the winter. Previous studies on dairy cow cold stress have considered thermal environmental factors but not physiological factors or air quality. Therefore, this study aimed to propose a multilevel fuzzy comprehensive evaluation (FCE) method for cold stress in dairy cows based on the analytic hierarchy process (AHP) and a genetic algorithm (GA). First, the AHP was used to construct an evaluation index system for cold stress in dairy cows from 3 dimensions: thermal environment (temperature, relative humidity, wind speed, and illumination), physiological factors (respiratory rate, body surface temperature), and air quality [NH3, CO2, inhalable particulate matter (PM10)]. Second, the consistency test of the judgment matrix was transformed into a nonlinear constrained optimization problem and solved using the GA. Next, based on fuzzy set theory, the comment set and membership function were established to classify the degree of cold stress into 5 levels: none, mild, moderate, high, and extreme. Then, the degree of cold stress in cows was obtained using multilevel fuzzy comprehensive judgment. To investigate the effect of illumination indicators on cold stress in dairy cows, 24 prelactation cows from the south and north sides were selected for a 117-d comprehensive cold stress evaluation. The results showed that the mean mild cold stress durations were 605.3 h (25.22 d) and 725.5 h (30.23 d) and the moderate cold stress durations were 67.2 h (2.8 d) and 96 h (4.0 d) on the south and north sides, respectively. Simultaneously, generalized linear mixed model showed that there were significant correlations between the daily cold stress duration and milk yield, feeding time, lying time, and active steps in the cows on both sides. This method can reasonably indicate cow cold stress conditions and better guide cold protection practices in actual production.

[Ruxolitinib combined with liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase in treatment of relapsed/refractory pediatric hemophagocytic lymphohistiocytosis].

Objective: To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of relapsed/refractory (R/R) pediatric hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical data of R/R pediatric HLH, who accepted the RU-DEP+/-L regimen at Beijing Children's Hospital from January 2018 to December 2019 was retrospectively analyzed. Results: A total of 16 patients were included in this study, including 13 males and 3 females, aged[M(Q1,Q3)] 1 (1, 2) years at diagnosis. Thirteen patients were diagnosed with Epstein-Barr virus (EBV)-HLH, 2 with EBV-induced primary HLH, and 1 with unclear etiology, among which 3 patients were co-infected with CMV. After the first-line treatment, 11 patients had no response, and 5 patients relapsed after complete response. Nine patients received the RU-L-DEP regimen, and 7 patients received the RU-DEP regimen. The overall response rate and complete response of RU-DEP+/-L treatment were 10/16 and 3/16, respectively. The negative conversion rate of plasma EBV-DNA was 7/15. The median follow-up time was 35.1 (2.4, 40.7) months, and 9/16 patients were survival. The 3-year overall survival rate after RU-DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation (HSCT) was higher than that without response and did not receive HSCT (P=0.048). Among the 16 patients, 9 had varying degrees of myelosuppression, and 13 had an infection. Conclusions: RU-DEP+/-L can be used as a salvage treatment in R/R pediatric HLH, which can provide a bridge to HSCT and play an important role in the control of HLH. The main adverse reactions are myelosuppression and infection, which can be tolerated.

[The value of spleen density in predicting prognosis of patients with gastric cancer after curative gastrectomy].

Objective: To investigate the value of spleen density in predicting the prognosis of patients with gastric cancer after radical gastrectomy. Methods: A total of 415 patients with gastric cancer who underwent radical resection in the Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from January 2012 to December 2015 were retrospectively analyzed. Of the patients, there were 295 males and 120 femles with a median age of 59 years (range 28-83 years). The patients were divided into diffuse decreased spleen density group (DROSD) (spleen density≤43.0 HU, n=118) and non-diffuse decreased spleen density group (N-DROSD) (spleen density>43.0 HU, n=297) according to the density of spleen detected by computed tomography (CT). The receiver operating characteristic (ROC) curve was used to identify the checkpoint of spleen density in predicting the recurrence of the gastric cancer in those patients. The relationship with clinicopathological factors and prognosis in the two groups were further analyzed. Results: The optimal critical value of spleen density for predicting postoperative recurrence of gastric cancer was 43.0 HU, the area under the curve of ROC was 0.608, and the sensitivity and specificity was 84.9% and 40.4%, respectively. Spleen density was related to albumin, hemoglobin, neutrophil lymphocyte ratio (NLR) and tumor diameter in patients with gastric cancer (all P<0.05). The 5-year disease-free survival rate and 5-year disease-specific survival rate of all the patients was 45.5% and 50.1%, respectively. Univariate survival analysis showed that age, NLR, PLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-free survival rate (all P<0.05); Age, NLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-specific survival rate (all P<0.05). Multivariate survival analysis showed that high NLR level (HR=1.501, 95%CI: 1.136-1.984), late TNM stage (HR=2.559, 95%CI: 1.850-3.539), DROSD (HR=2.093, 95%CI: 1.571-2.788) and no adjuvant chemotherapy (HR=1.583, 95%CI: 1.204-2.083) were independent risk factor for the 5-year disease-free survival rate (all P<0.05). Late TNM stage (HR=1.938, 95%CI: 1.395-2.692), DROSD (HR=1.566, 95%CI: 1.180-2.078) and no adjuvant chemotherapy (HR=1.336, 95%CI: 1.016-1.758) were independent risk factors for the 5-year disease-free survival rate (all P<0.05). For stage Ⅰ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 78.6% and 83.7%, respectively; and the 5-year disease-specific survival rates was 85.7% and 89.8%, respectively (both P>0.05). For stage Ⅱ and Ⅲ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 15.4% and 48.8%, respectively, and the 5-year disease-specific survival rates was 17.3% and 54.0%, respectively (all P<0.001). Conclusion: As an imaging evaluation method, spleen density is a new tool, which can be used as a prognostic indicator for gastric cancer patients.

[Clinical analysis of fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of 43 cases of chronic lymphoblastic leukemia].

Objective: To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) . Methods: The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results. Results: A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10(9)/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS (P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS (P<0.001) , and the prognostic value still remained after multivariate analysis[HR=7.65 (95%CI 1.74-33.60) , P=0.007; HR=3.75 (95%CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion: Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.

Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration.

Intrauterine adhesions (IUAs) refer to the repair disorder after endometrial injury and may lead to uterine infertility, recurrent miscarriage, abnormal menstrual bleeding, and other obstetric complications. It is a pressing public health issue among women of childbearing age. Presently, there are limited clinical treatments for IUA, and there is no sufficient evidence that these treatment modalities can effectively promote regeneration after severe endometrial injury or improve pregnancy outcome. The inhibitory pathological micro-environment is the main factor hindering the repair of endometrial damaged tissues. To address this, tissue engineering and regenerative medicine have been achieving promising developments. Particularly, biomaterials have been used to load stem cells or therapeutic factors or construct an in situ delivery system as a treatment strategy for endometrial injury repair. This article comprehensively discusses the characteristics of various bio-scaffold materials and their application as stem cell or therapeutic factor delivery systems constructed for uterine tissue regeneration.

[Central nervous system toxicity caused by bortezomib: five case reports and a review of literature].

Objective: To investigate the clinical features, diagnosis, and treatment of the central nervous system (CNS) toxicity caused by bortezomib. Methods: This study reports five new cases of CNS toxicity caused by bortezomib to elucidate its characteristics along with a review of the literature. Results: CNS toxicity caused by bortezomib presents in three clinical forms: syndrome of inappropriate antidiuresis (SIAD) , posterior reversible encephalopathy syndrome (PRES) , and central fever, which is the most common clinical manifestation. Four of our five patients developed central fever after the administration of bortezomib, manifested as persistent high fever, anhidrosis, and absence of infective foci; the symptom could be improved by discontinuance of bortezomib. Of these patients, three concurrently presented with refractory hyponatremia and one was clearly diagnosed with SIAD. The bortezomib could have caused damages to the hypothalamus and induced both central fever and SIAD. In addition, one patient was diagnosed with PRES due to disturbance of consciousness and epilepsy after taking bortezomib. After discontinuation of bortezomib, the symptoms disappeared and did not recur. We also found that thrombocytopenia may be related to the severity of the CNS toxicity of bortezomib. Conclusion: Cases of CNS toxicity of bortezomib are extremely rare and present as SIAD, PRES and central fever. Early detection and treatment of bortezomib are very important to prevent irreversible neurological complications.

[Expression of LIAS and NRF2 in PBMCs from patients with silicosis and their correlation with silicosis].

Objective: To investigate the expression of lipoic acid synthase gene (LIAS) and nuclear factor-erythroid 2-related factor 2 gene (NRF2) in peripheral blood mononuclear cells (PBMCs) from patients with silicosis and their correlation with silicosis. Methods: A total of 45 healthy controls and 107 patients with silicosis were randomly selected in this study in May 2019. PBMCs were isolated from peripheral blood and NRF2 protein expression was detected by immunofluorescence. The mRNA levels of LIAS and NRF2 in PBMCs were determined by real-time PCR. The dose-response relationship beween LIAS and NRF2 mRNA expression levels and their association with silicosis were analyzed by restricted cubic spline (RCS) and logistic regression. Results: Compared with the control group, the number of monocytes in the case group was significantly increased, and the forced expiratory volume in the first second (FEV(1.0)) decreased, the difference was statistically significant (P<0.05) . The positive expression rate of NRF2 in PBMCs of silicosis patients in stage Ⅰ group was significantly higher than that in the control group, and the positive expression rate of NRF2 in silicosis patients in stageⅡ and Ⅲ groups was lower than that in silicosis patients in control group and stage Ⅰ group (P<0.01) . Results of RCS showed that there was a linear dose-response relationship between LIAS and NRF2 mRNA expression (overall correlation test, χ(2)=213.710, P<0.01; non-linear test, χ(2)=1.340, P=0.511) . There was a positive correlation between mRNA expression of LIAS and that of NRF2 (r=0.651, P<0.01) . The results of multivariate analysis showed that LIAS and NRF2 were increased the risk of incidence in silicosis patients with stageⅠ (OR=11.184, 4.332, P<0.05) and NRF2 was the protective factor in silicosis patients with stage Ⅱ and Ⅲ (OR=0.225, 0.208, P<0.05) after adjusting for potential confounding factors including age, education level, BMI and smoking. Conclusion: There is a linear dose-response relationship between the expression of LIAS and NRF2 mRNA in PBMCs of silicosis patients, LIAS and NRF2 are involved in the pathogenesis of silicosis.

[Application of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy].

Objective: To explore the application value of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy. Methods: The retrospective cohort study was conducted. The clinicopathological data of 82 patients with gastric cancer who were admitted to Henan Tumor Hospital from April 2016 to April 2019 were collected. 38 patients who used carbon nanoparticles labeled node staining were in the observation group, while other 44 patients were in the control group. Data analysis including the operation and results of harvested of lymph nodes. Results: All patients successfully completed the operation.Thirty-eight patients successfully completed the injection of carbon nanoparticles. Surgery: observation group operating time was (150±28) min, intraoperative blood loss was (207±121) ml, group operating time was (140±23) min, intraoperative blood loss was (256±182) ml. There was no statistically significant difference between the two groups. Detection of Lymph node: A total of 1 260 lymph nodes were detected in the observation group and 981 in the control group. In the observation group, the mean lymph node sorting time was (17.2±3.3) min, the average number of harvested lymph node was 33.2±10.4, the number of the first station of lymph node was 19.8±5.3, the second station of lymph node was 13.4±6.4, the number of harvested small node(<5 mm) was 673, the positive lymph nodes was 13(range,1-31). They were all higher than those in the control group, which were (20.6±4.4)min,22.3±6.6, 12.6±4.1, 9.7±3.2,432,6 (range,1-13) , respectively. The difference between the two groups was statistically significant (P<0.05). The metastasis rate was 19.1% (241/1 260) in observation group and 16.5%(162/981) in the control group. The difference was no statistical(P>0.05). The rate of black -dyed harvested lymph node was 54.4%(686/1 260) in carbon nanoparticles group. Conclusions: The application of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy is feasible and safe. It can increase the number of lymph nodes detected, which is beneficial to the evaluation of chemotherapy effect and prognosis of patients.