Objective To evaluate the efficacy and safety of obinutuzumab(OBZ)in the treatment of refractory primary membranous nephropathy(pMN).Methods The clinical data of 15 patients with refractory pMN who received OBZ treatment in Department of Nephrology of The First Affiliated Hospital of Naval Medical University between Jan.2022 and Sep.2024 were retrospectively analyzed,and they included basic information,relevant laboratory indexes,clinical and immunological outcomes,and adverse events.Results Among the 15 patients with refractory pMN,14(93.3％)were phospholipase A2 receptor(PLA2R)-associated membranous nephropathy(10 cases with positive PLA2R by renal biopsy and 4 cases with no recorded PLA2R results by renal biopsy but with positive serum PLA2R antibodies).During the follow-up period,all 15 patients achieved clinical remission,with 4(26.7％)patients achieving complete remission and 11(73.3％)patients achieving partial remission.Of the 12 patients with positive serum PLA2R antibodies,11 patients had continuously positive serum PLA2R antibodies before OBZ treatment,and 9(81.8％)patients achieved immunological remission after OBZ treatment.All the 15 patients had previously received immunosuppressive therapy,and all of them were classified as refractory pMN,with 7(46.7％)patients having been treated with cyclophosphamide combined with corticosteroids,2(13.3％)patients having been treated with calcineurin inhibitor combined with corticosteroids,11(73.3％)patients having received rituximab.During the treatment,2(13.3％)cases of adverse events were observed:1 patient experienced transient liver dysfunction,and the transaminase returned to normal after discontinuing atorvastatin;another patient developed a positive T-cell spot test for Tuberculosis infection during the intertreatment interval and successfully completed the subsequent OBZ treatment and achieved clinical remission after treatment with isoniazid and rifampicin.Conclusion OBZ demonstrates favorable clinical efficacy in the treatment of refractory pMN,with a low incidence of adverse events.

Objective:To investigate the classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy (LPD).Methods:The records of 51 consecutive patients with LPD who were treated by linear staple closure technique of pancreatic neck from February to December 2022 from Binzhou Second People′s Hospital, Shijingshan Campus, Beijing Chaoyang Hospital, Capital Medical University, Rizhao Hepatobiliary-Pancreatic-Splenic Surgery Research Institute, Chaoyang Central Hospital, Shandong Juxian People′s Hospital, Weihai Municipal Hospital, Binzhou Central Hospital, and Affiliated Hospital of Chifeng University were retrospectively reviewed. According to the visibility, position and diameter of the main pancreatic duct at the stump of the pancreas, the type of main pancreatic duct was divided into type I, type Ⅱ, type Ⅲa and type Ⅲb. The number of cases in each main pancreatic duct classification and the corresponding treatment strategies were examined.Results:A total of 51 cases of LPD were successfully completed. Of these patients, the males comprised 56.9%(29/51), and females comprised 43.1%(22/51), with age ranging from 31 to 88 years old. The type of the main pancreatic duct at the stump of the pancreas included 7 cases (13.7%) of type Ⅰ, 39 cases (76.5%) of type Ⅱ, 2 cases (3.9%) of type Ⅲa, and 3 cases (5.9%) of type Ⅲb. Corresponding treatment strategies were adopted according to different main pancreatic duct types, the main pancreatic duct was successfully found, and a support drainage tube was inserted.Conclusion:After linear stapler closure of pancreatic neck, corresponding treatment strategies should be adopted according to the classification of the main pancreatic duct, which would help to improve the success rate of finding the main pancreatic duct and placing a support drainage tube.

BACKGROUND:Classical drug for Parkinson’s disease is levodopa, but long-term application of levodopa can induce complications such as dyskinesias.
OBJECTIVE:To observe the effects of levodopa on learning and memory capacities of Parkinson’s disease rats and to study its mechanisms.
METHODS:The rat models of Parkinson’s disease were established using 6-hydroxydopamine. The 228 model rats were randomly divided into control group and experimental group. Rats in the experimental group were intraperitoneal y injected with 10, 20 and 30 mg/(kg?d) levodopa for 28 consecutive days. At 1, 3, 5, 7, 14 and 28 days after intraperitoneal injection, we observed the rats’ learning and memory capacities and tested plasma concentration of homocysteine and folic acid. Acetylcholinesterase activities in the rat hippocampus were measured. Hippocampal neurofibril ary tangles were observed using Bielschowsky staining.
RESULTS AND CONCLUSION:Increased dose of levodopa and prolonged application time obviously decreased learning and memory capacities in rats (P<0.001), increased plasma homocysteine levels, reduced folic acid levels (P<0.001), diminished acetylcholine esterase activities in the rat hippocampus (P<0.001), and increased neurofibril ary tangles in the rat hippocampus (P=0.000). Results suggested that a large dose of levodopa could significantly decrease the learning and memory capacities, and disease acetylcholine esterase activities, and increase neurofibril ary tangles in hippocampus. Its mechanism possibly associated with the increased plasma concentration of homocysteine.

The generation of large quantities of novel human T cell clones ex vivo would make a wide range of gene-and immuno-therapies for tumor and AIDS possibly. Although it is well established that T cells are derived from CD34(+) cells, the involvement of thymic fragments from either human or murine fetus makes the in vitro T cell perliferation very cumbersome. In this report, cord blood mononuclear cells were used as accessory cells to support the differentiation of CD34(+) cells into naive T cells stimulated with SCF and IL-2. CD4(+) and CD8(+) T cells, under the cultural conditions, were continuously produced in vitro at least over a period of 3 weeks and their ratios changed gradually. CD4/CD8 double positive T cells and RAG-2 gene were existed, and RAG-2 gene, reponsible for TCR rearrangement, was expressed during the cell proliferation. Our study presents a simple culture system in vitro to acquire large quantities of naive T cell clones.