OBJECTIVE To screen potential adverse drug event （ADE） signals for the treatment of multiple sclerosis （MS） with ofatumumab， and to provide reference for the safe use of drugs in clinical practice. METHODS Using “ofatumumab” and the trade name “Kesimpta” as the search keywords， adverse event （AE） reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened， and their reason contained the “multiple sclerosis”； ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method. RESULTS A total of 21 759 eligible AE reports were selected， involving 62 449 AE cases； 27 system organ classes included general diseases and various reactions at the site of administration （15 021 cases）， neurological diseases （9 668 cases）， infectious and invasive diseases （5 967 cases）， injury， poisoning and surgical complications （4 952 cases）， musculoskeletal and connective tissue disorders （4 647 cases）. A total of 21 759 AE reports correspond to 606 ADE signals， including 234 ADE positive signals. A total of 107 ADE positive signals were not included in drug instruction of ofatumumab， including flu-like diseases， nasopharyngitis， cough， urinary tract infection， sore throat， insomnia， runny nose， anemia， hair loss， atrial fibrillation， and thrombocytopenia， etc. CONCLUSIONS In the process of using ofatumumab for MS， sufficient attention should be paid to ADE included in drug instructions. The ADE with strong signal strength screened in this study should also be paid special attention to， such as flu-like diseases， hemocytopenia， temperature intolerance， optic neuritis， and moyamoya disease. The increased risk of infection， cardiovascular disease， and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

Objective:To explore the clinical features of immunocompetent primary central nervous system lymphoma (PCNSL) and influencing factors for prognosis of immunocompetent patients with PCNSL.Methods:A retrospective analysis was performed; 69 immunocompetent patients with PCNSL confirmed by pathology in First Medical Center of PLA General Hospital from January 2016 to January 2024 were enrolled; initial symptoms, Eastern Cooperative Oncology Group (ECOG) score, and results of laboratory and pathological examinations in these patients were collected. Patients were divided into biopsy confirmed group ( n=43) and lesion resection confirmed group ( n=26) according to different diagnostic methods; patients were also divided into chemotherapy group ( n=48), chemotherapy+radiotherapy group ( n=9) and surgical resection group ( n=12) according to different treatment methods. Clinical outcomes of these patients in different groups at the end of follow-up were compared, and the influencing factors for short-term prognosis (6 months after treatment) were identified. All patients were followed up for 12.80 (6.00, 36.40) months. The short-term prognosis was evaluated by modified Rankin scale (mRS) 6 months after treatment (mRS scores of 0-2: good prognosis; mRS scores of 3-6: poor prognosis). Overall survival (OS) was recorded at the end of follow-up. Results:Among the 69 immunocompetent patients with PCNSL, 37 were males and 32 were females; median onset age was 59 years, ranged 24-83 years. Focal neurologic deficits of different degrees (34/69, limb weakness, sensory disturbances, ataxia, or eye involvement) were the most common initial symptoms, followed by headache (14/69), dizziness (10/69), cognitive dysfunction (9/69), epilepsy (1/69) and psychiatric disorders (1/69). Forty-five patients underwent cerebrospinal fluid examination: 17 had cerebrospinal fluid pressure≥200 mmH 2O (1 mmH 2O=9.8 Pa); 10 had increased white blood cell count (>10×10 6/L), reaching to (16.5[11.0, 20.0])×10 6/L; 32 had increased protein level, reaching to 758.10 (547.83, 948.13) mg/L. Cerebrospinal fluid cytology was performed in 15 patients, and tumor cells were found in only 1 patient. Cranial MRI showed that intracranial solitary lesions were more common (60.87%, 42/69), and most lesions were at the basal ganglia region (40.58%, 28/69). PET/CT showed a obviously higher metabolism of the lesions (97.06, 33/34), with maximum standardized uptake of 22.9 (13.9, 30.55) g/mL. All patients had diffuse large B-cell lymphoma (DLBCL). By the end of follow-up, 28 patients died. Logistic regression analysis showed that ECOG score≥2 ( OR=9.210, 95% CI: 2.558-32.896, P=0.001) and positive MYC ( OR=0.088, 95% CI: 0.008-0.973, P=0.047) were independent risk factors for poor short-term prognosis. Cox proportional hazard regression model analysis showed that ECOG score≥2 ( HR=5.135, 95% CI: 2.230-11.827, P<0.001), positive B-cell lymphoma 6 (BCL-6, HR=0.226, 95% CI: 0.079-0.649, P=0.006) and chemotherapy or chemotherapy+radiotherapy ( HR=0.392, 95% CI: 0.157-0.980, P=0.045) were independent prognostic factors for OS. Conclusions:In immunocompetent patients with PCNSL, focal neurological deficits are more common at the onset, and fever is rare. Patients with ECOG score≥2 are more likely to have poor short-term prognosis and short OS. MYC-positive patients will have a better short-term prognosis; BCL-6 positive patients and patients treated with chemotherapy or chemotherapy+radiotherapy will have longer OS.

Objective:To explore the clinical features of immunocompetent primary central nervous system lymphoma (PCNSL) and influencing factors for prognosis of immunocompetent patients with PCNSL.Methods:A retrospective analysis was performed; 69 immunocompetent patients with PCNSL confirmed by pathology in First Medical Center of PLA General Hospital from January 2016 to January 2024 were enrolled; initial symptoms, Eastern Cooperative Oncology Group (ECOG) score, and results of laboratory and pathological examinations in these patients were collected. Patients were divided into biopsy confirmed group ( n=43) and lesion resection confirmed group ( n=26) according to different diagnostic methods; patients were also divided into chemotherapy group ( n=48), chemotherapy+radiotherapy group ( n=9) and surgical resection group ( n=12) according to different treatment methods. Clinical outcomes of these patients in different groups at the end of follow-up were compared, and the influencing factors for short-term prognosis (6 months after treatment) were identified. All patients were followed up for 12.80 (6.00, 36.40) months. The short-term prognosis was evaluated by modified Rankin scale (mRS) 6 months after treatment (mRS scores of 0-2: good prognosis; mRS scores of 3-6: poor prognosis). Overall survival (OS) was recorded at the end of follow-up. Results:Among the 69 immunocompetent patients with PCNSL, 37 were males and 32 were females; median onset age was 59 years, ranged 24-83 years. Focal neurologic deficits of different degrees (34/69, limb weakness, sensory disturbances, ataxia, or eye involvement) were the most common initial symptoms, followed by headache (14/69), dizziness (10/69), cognitive dysfunction (9/69), epilepsy (1/69) and psychiatric disorders (1/69). Forty-five patients underwent cerebrospinal fluid examination: 17 had cerebrospinal fluid pressure≥200 mmH 2O (1 mmH 2O=9.8 Pa); 10 had increased white blood cell count (>10×10 6/L), reaching to (16.5[11.0, 20.0])×10 6/L; 32 had increased protein level, reaching to 758.10 (547.83, 948.13) mg/L. Cerebrospinal fluid cytology was performed in 15 patients, and tumor cells were found in only 1 patient. Cranial MRI showed that intracranial solitary lesions were more common (60.87%, 42/69), and most lesions were at the basal ganglia region (40.58%, 28/69). PET/CT showed a obviously higher metabolism of the lesions (97.06, 33/34), with maximum standardized uptake of 22.9 (13.9, 30.55) g/mL. All patients had diffuse large B-cell lymphoma (DLBCL). By the end of follow-up, 28 patients died. Logistic regression analysis showed that ECOG score≥2 ( OR=9.210, 95% CI: 2.558-32.896, P=0.001) and positive MYC ( OR=0.088, 95% CI: 0.008-0.973, P=0.047) were independent risk factors for poor short-term prognosis. Cox proportional hazard regression model analysis showed that ECOG score≥2 ( HR=5.135, 95% CI: 2.230-11.827, P<0.001), positive B-cell lymphoma 6 (BCL-6, HR=0.226, 95% CI: 0.079-0.649, P=0.006) and chemotherapy or chemotherapy+radiotherapy ( HR=0.392, 95% CI: 0.157-0.980, P=0.045) were independent prognostic factors for OS. Conclusions:In immunocompetent patients with PCNSL, focal neurological deficits are more common at the onset, and fever is rare. Patients with ECOG score≥2 are more likely to have poor short-term prognosis and short OS. MYC-positive patients will have a better short-term prognosis; BCL-6 positive patients and patients treated with chemotherapy or chemotherapy+radiotherapy will have longer OS.

Objective:To investigate the overlapping prevalence and risk factors of gastroesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) among rural adults in Shaanxi Province.Methods:From February 1 to October 31 in 2019, 12 villages in Shaanxi Province were randomly selected for household questionnaire survey through multistage stratified cluster sampling. A total of 2 423 subjects were enrolled, including 1 037 males and 1 386 females, with age of (45.3±16.9) years old. GERD was diagnosed according to the Montreal criteria, FD and IBS were diagnosed according to the Rome Ⅳ criteria. The overlapping prevalence of the three diseases were calculated. The risk factors for the overlapping of GERD, FD and IBS were analyzed. Multivariate logistic regression was used for statistical analysis.Results:Among the 2 423 subjects, 624 cases had GERD (302 cases), FD (377 cases) or IBS (167 cases), of which 30.77% (192/624) patients had overlap of ≥two diseases. The overlap rates of GERD and FD, GERD and IBS, FD and IBS, GERD, FD and IBS were 2.56% (62/2 423), 1.61% (39/2 423), 2.52% (61/2 423) and 1.24% (30/2 423), respectively. The results of Multivariate analysis showed that female and migraine without aura were positively correlated with the overlap of GERD and FD, FD and IBS, and GERD and IBS (odds ratio ( OR)=3.08, 2.68, 3.66, 7.37, 5.91 and 4.46, 95% confidence interval ( CI) 1.35 to 7.01, 1.35 to 5.30, 1.52 to 8.83, 3.97 to 13.69, 1.78 to 19.60 and 2.01 to 9.92; all P<0.05). Heavy drinking (alcohol intake≥50 g/d (male) or≥30 g/d (female)) was positively correlated with the overlap of FD and IBS, GERD and IBS, and GERD, FD and IBS ( OR=3.69, 4.20 and 4.91, 95% CI 1.19 to 11.48, 1.01 to 17.50 and 1.23 to 19.52; all P<0.05). Heavy smoking (smoking≥20 cigarettes per day) was positively correlated with the overlap of GERD and FD, FD and IBS, GERD and IBS, and GERD, FD and IBS ( OR=3.44, 6.25, 8.27 and 7.04, 95% CI 1.07 to 11.01, 1.60 to 24.44, 1.80 to 38.07 and 1.76 to 28.12; all P<0.05). The educational level of junior or senior high school and age≥60 years old were negatively correlated with the overlap of GERD and FD, FD and IBS, GERD and IBS, and GERD, FD and IBS ( OR=0.47, 0.29, 0.20, 0.05, 0.23, 0.10, 0.37 and 0.16, 95% CI 0.23 to 0.93, 0.09 to 0.95, 0.09 to 0.42, 0.01 to 0.19, 0.09 to 0.60, 0.02 to 0.65, 0.15 to 0.87 and 0.03 to 0.81; all P<0.05). Conclusions:The overlap of GERD, FD and IBS is common and affected by many factors. Female, age≥60 years old, heavy smoking, heavy drinking, low education level and history of migraine without aura are associated with multiple overlaps of GERD, FD and IBS.

Background: Previous studies have found that patients with gastrointestinal diseases have a higher incidence of headache, while migraine patients are often accompanied by gastrointestinal symptoms. Understanding the relationship between diseases can provide new ideas for the study of its mechanism. Aims: To explore the co-occurrence and related risk factors of gastroesophageal reflux disease (GERD), functional dyspepsia (FD), irritable bowel syndrome (IBS) and migraine without aura (MWoA). Methods: A total of 2 696 adult rural residents in Shaanxi Province were investigated by random stratified sampling. MWoA, GERD, FD and IBS were diagnosed based on ICHD-IIIβ, Montreal classification and Rome , respectively. The prevalence of the single disease and overlapping prevalence of MWoA were calculated. The prevalence rates of GERD, FD and IBS between MWoA group and non-MWoA group were compared, and the disease-related risk factors were analyzed. Results: In this study, a total of 2 423 valid questionnaires were collected. The prevalence rates of GERD, FD and IBS were 12.5%, 15.6% and 6.9%, respectively, and the prevalence rate of MWoA was 8.8%. The prevalence rates of GERD (30.5% vs. 10.7%), FD (37.1% vs. 13.5%) and IBS (27.2% vs. 4.9%) in MWoA group were all higher than those in non-MWoA group (P all < 0.001). Multivariate analysis showed that female, hypertension, chronic motor system diseases were positively correlated with GERD, FD, IBS and MWoA. Conclusions: There is a certain association between GERD, FD, IBS and MWoA.

Objective To explore the effect and mechanism of necroptosis related proteins in middle cerebral artery occlusion (MCAO) induced brain ischemia/reperfusion injury in mice.Methods C57BL/6 mice were used to establish the brain ischemia/reperfusion injury model induced by MCAO.MCAO mice were treated with z-VAD.fmk (zVAD,1.1 g/kg),GSK'872 (0.7 g/kg) and combined intervention of zVAD and GSK'872,and neurological defect was evaluated by mNSS while brain infarct volume was measured by TTC staining.Western blot and immunofluorescence assay were used to detect protein expression and location of RIP1,RIP3 and MLKL,respectively.Results Neurological defect and brain infarction were caused by MCAO.Compared with MCAO group,zVAD,GSK'872 and the combined intervention alleviated neurological defect and reduced brain infarct volume significantly (P＜0.05 or P＜0.01).The protein levels of RIP3 and RIP1 MLKL were increased in mice of MCAO group,while GSK'872 and the combined intervention obviously downregulated the aforementioned protein expression [RIP1 (GSK'872:0.64± 0.02 vs MCAO:1.28±0.02,P＜0.01);RIP3 (GSK'872:1.08±0.02 vs MCAO:1.45±0.02,P＜0.01);MLKL (GSK'872:0.54±0.01 vs MCAO:1.00±0.01,P＜0.01)].However,zVAD only slightly reduced protein expression of MLKL (P＜0.05) but didn't change the protein expression of RIP1 and RIP3 (P＞0.05).Conclusion RIP1,RIP3 and MLKL are involved in the execution of necroptosis and contribute to the pathological progress of brain ischemia/reperfusion injury.

Hospital acquired infection (HAI) is one of the common complications of hospitalized patients and poses a serious threat to public health worldwide, which causes an exacerbation, prolonged hospitalization and increased medical costs. Because of higher illness severity and more invasive operations, patients in neurosurgical intensive critical unit (NICU) are more susceptible to HAI such as hospital acquired pneumonia (HAP) and surgical site infection (SSI), leading to theincrease of mortality. Therefore, the prevention and treatment of HAI is an important challenge during the treatment of diseases in NICU. In this paper, we summarized the common types, pathogenic characteristics, prevention measures and antimicrobial treatment of HAI in NICU, aiming to provide ideas and reference on HAI treatment for medical personnel in NICU.