Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.

Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)％,(26.91±2.94)％,(19.28±1.52)％and(6.33±2.30)％;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P＜0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

Objective To explore the mechanism of inhibition of colorectal cancer cells HT29 proliferation,migration and invasion by bufalin through Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Human colorectal cancer HT29 cells were randomly divided into control group and experimental-L,-M,-H groups.The cells in the control group were not treated,and the cells in the experimental-L,-M,-H groups were treated with 2.5,5.0 and 10.0 μmol·L-1 bufalin for 48 h.After HT29 cells were infected with FLAG STAT3 lentivirus,the cells were divided into lentivirus infection group and experiment-H(10.0 pmol·L-1 bufalin)+lentivirus infection group.Cell viability was detected by cell counting kit 8(CCK-8).Cloning experiment to verify cell proliferation rate;Transwell experiment verified the migration ability of cells after bufalin treatment;the transfection efficiency of lentivirus and the expression of cell-related proteins were detected by Western blot.Results After 48 h of drug action,the number of cells in the control group,experimental-L,-M,-H groups were 1 003.25±255.53,698.00±152.25,562.13±31.56 and 449.50±82.40,respectively;the number of invasive cells were 932.00±188.84,742.22±108.64,514.67±124.82 and 343.56±86.42,respectively;the protein expression level of p-JAK2 were 1.37±0.27,0.97±0.06,0.74±0.06 and 0.39±0.12,respectively.The number of cells in the control group,experimental-H group,lentivirus infection group,and experimental-H+lentivirus infection group were 906.88±211.71,389.00±143.08,1 279.38±210.34 and 604.75±12.52,respectively;the number of invasive cells were 671.22±44.74,246.11±28.16,1 080.78±119.13 and 574.78±16.23,respectively.Compared with the control group,there were statistically significant differences in the number of cell proliferation,the number of cell invasion and the relative levels of p-JAK2 in the experimental-M and-H groups(all P＜0.05).Compared with the control group,the number of cell proliferation and the number of cell invasion in the experimental-H group,the lentivirus infection group,and the high-dose experimental+lentivirus infection group were statistically significant(all P＜0.05).Conclusion Bufalin can inhibit the proliferation,migration and invasion of colorectal cancer by activating the JAK2/STAT3 signalling pathway.

Objective: To observe the expansion rule of directional skin and soft tissue expander (hereinafter referred to as expander) in abdominal scar reconstruction. Methods: A prospective self-controlled study was conducted. Twenty patients with abdominal scar who met the inclusion criteria and admitted to Zhengzhou First People's Hospital from January 2018 to December 2020 were selected by random number table method, including 5 males and 15 females, aged 12-51 (31±12) years, with 12 patients of type Ⅰ scar and 8 patients of type Ⅱ scar. In the first stage, two or three expanders with rated capacity of 300-600 mL were placed on both sides of the scar, of which at least one expander had rated capacity of 500 mL (as the follow-up observation object). After the sutures were removed, water injection treatment was started, with the expansion time of 4 to 6 months. After the water injection volume reached 2.0 times of the rated capacity of expander, abdominal scar excision+expander removal+local expanded flap transfer repair was performed in the second stage. The skin surface area at the expansion site was measured respectively when the water injection volume reached 1.0, 1.2, 1.5, 1.8, and 2.0 times of the rated capacity of expander, and the skin expansion rate of the expansion site at corresponding multiples of expansion (1.0, 1.2, 1.5, 1.8, and 2.0 times) and adjacent multiple intervals (1.0-1.2, 1.2-1.5, 1.5-1.8, and 1.8-2.0 times) were calculated. The skin surface area of the repaired site at 0 (immediately), 1, 2, 3, 4, 5, and 6 months after operation, and the skin shrinkage rate of the repaired site at different time points (1, 2, 3, 4, 5, and 6 months after operation) and different time periods (0-1, 1-2, 2-3, 3-4, 4-5, and 5-6 months after operation) were calculated. Data were statistically analyzed with analysis of variance for repeated measurement and least significant difference-t test. Results: Compared with the expansion of 1.0 time ((287.6±2.2) cm² and (47.0±0.7)%), the skin surface area and expansion rate of the expansion site of patients ((315.8±2.1), (356.1±2.8), (384.9±1.6), and (386.2±1.5) cm², (51.7±0.6)%, (57.2±0.6)%, (60.4±0.6)%, and (60.5±0.6)%) were significantly increased when the expansion reached 1.2, 1.5, 1.8, and 2.0 times (with t values of 46.04, 90.38, 150.14, 159.55, 45.11, 87.83, 135.82, and 118.48, respectively, P<0.05). Compared with the expansion of 1.2 times, the skin surface area and expansion rate of the expansion site of patients were significantly increased when the expansion reached 1.5, 1.8, and 2.0 times (with t values of 49.82, 109.64, 122.14, 144.19, 49.51, and 105.85, respectively, P<0.05). Compared with the expansion of 1.5 times, the skin surface area and expansion rate of the expansion site of patients were significantly increased when the expansion reached 1.8 times (with t values of 38.93 and 39.22, respectively, P<0.05) and 2.0 times (with t values of 38.37 and 38.78, respectively, P<0.05). Compared with the expansion of 1.8 times, the skin surface area and expansion rate of the expansion site of patients both had no statistically significant differences when the expansion reached 2.0 times (with t values of 4.71 and 4.72, respectively, P>0.05). Compared with the expansion of 1.0-1.2 times, the skin expansion rate of the expansion site of patient was significantly increased when the expansion reached 1.2-1.5 times (t=6.95, P<0.05), while the skin expansion rate of the expansion site of patient was significantly decreased when the expansion reached 1.5-1.8 and 1.8-2.0 times (with t values of 5.89 and 40.75, respectively, P<0.05). Compared with the expansion of 1.2-1.5 times, the skin expansion rate of the expansion site of patient was significantly decreased when the expansion reached 1.5-1.8 and 1.8-2.0 times (with t values of 10.50 and 41.92, respectively, P<0.05). Compared with the expansion of 1.5-1.8 times, the skin expansion rate of the expansion site of patient was significantly decreased when the expansion reached 1.8-2.0 times (t=32.60, P<0.05). Compared with 0 month after operation, the skin surface area of the repaired site of patient at 1, 2, 3, 4, 5, and 6 months after operation was significantly decreased (with t values of 61.66, 82.70, 96.44, 102.81, 104.51, and 102.21, respectively, P<0.05). Compared with 1 month after operation, the skin surface area of the repaired site of patient was significantly decreased at 2, 3, 4, 5, and 6 months after operation (with t values of 37.37, 64.64, 69.40, 72.46, and 72.62, respectively, P<0.05), while the skin shrinkage rate was significantly increased (with t values of 32.29, 50.00, 52.67, 54.76, and 54.62, respectively, P<0.05). Compared with 2 months after operation, the skin surface area of the repaired site of patient was significantly decreased at 3, 4, 5, and 6 months after operation (with t values of 52.41, 60.41, 70.30, and 65.32, respectively, P<0.05), while the skin shrinkage rate was significantly increased (with t values of 52.97, 59.29, 69.68, and 64.50, respectively, P<0.05). Compared with 3 months after operation, the skin surface area of the repaired site of patient was significantly decreased at 4, 5, and 6 months after operation (with t values of 5.53, 38.00, and 38.52, respectively, P<0.05), while the skin shrinkage rate was significantly increased (with t values of 25.36, 38.59, and 37.47, respectively, P<0.05). Compared with 4 months after operation, the skin surface area (with t values of 41.10 and 50.50, respectively, P>0.05) and skin shrinkage rate (with t values of 48.09 and 50.00, respectively, P>0.05) of the repaired site of patients at 5 and 6 months after operation showed no statistically significant differences. Compared with 5 months after operation, the skin surface area and skin shrinkage rate of the repaired site of patient at 6 months after operation showed no statistically significant differences (with t values of 9.40 and 9.59, respectively, P>0.05). Compared with 0-1 month after operation, the skin shrinkage rate of the repaired site of patient at 1-2, 2-3, 3-4, 4-5, and 5-6 months after operation was significantly decreased (with t values of 13.56, 40.00, 49.21, 53.97, and 57.68, respectively, P<0.05). Compared with 1-2 months after operation, the skin shrinkage rate of the repaired site of patients at 2-3, 3-4, 4-5, and 5-6 months after operation was significantly decreased (with t values of 12.37, 27.72, 30.16, and 31.67, respectively, P<0.05). Compared with 2-3 months after operation, the skin shrinkage rate of the repaired site of patients at 3-4, 4-5, and 5-6 months after operation was significantly decreased (with t values of 33.73, 41.31, and 54.10, respectively, P<0.05). Compared with 3-4 months after operation, the skin shrinkage rate of the repaired site of patient at 4-5 and 5-6 months after operation showed no statistically significant differences (with t values of 10.90 and 23.60, respectively, P>0.05). Compared with 4-5 months after operation, the skin shrinkage rate of the repaired site of patient at 5-6 months after operation showed no statistically significant difference (t=20.90, P>0.05). Conclusions: The expander can effectively expand the abdominal skin, thus repairing the abdominal scar deformity. Maintained expansion for one month after the water injection expansion reaches 1.8 times of the rated capacity of the expander can be set as a phase Ⅱ operation node.
Female ; Male ; Humans ; Cicatrix/surgery* ; Prospective Studies ; Tissue Expansion Devices ; Skin ; Abdominal Wall

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Adult ; Humans ; Acute Disease ; Leukemia

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective: To explore the clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 12 male patients with thumb destructive defects caused by electrical burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 27 to 58 years, including 10 cases with degree Ⅲ thumb defect and 2 cases with degree Ⅳ thumb defect after thorough debridement. The thumb was reconstructed with free hallux-nail flap combined with composite tissue flap of the second phalangeal bone, joint, and tendon with skin island. The donor site of hallux-nail flap was covered with artificial dermis in the first stage and performed with continuous vacuum sealing drainage, and covered with medium-thickness skin graft from the groin site in the second stage. The donor site in the second toe was filled and fixed with iliac bone strips. The survival of reconstructed thumb was observed 1 week after the reconstruction surgery, the survival of skin graft in the donor site of hallux-nail flap was observed 2 weeks after skin grafting, and the callus formation of the reconstructed thumb phalanx and the second toe of the donor foot was observed by X-ray 6 weeks after the reconstruction surgery. During the follow-up, the shape of reconstructed thumb was observed and the sensory function was evaluated; the function of reconstructed thumb was evaluated with trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association; whether the interphalangeal joints of the hallux and the second toe were stiff, the scar hyperplasia of the foot donor site, and whether the walking and standing functions of the donor feet were limited were observed. Results: One week after the reconstruction surgery, all the reconstructed thumbs of the patients survived. Two weeks after skin grafting, the skin grafts in the donor site of hallux-nail flap of 11 patients survived, while the skin graft in the donor site of hallux-nail flap of 1 patient was partially necrotic, which was healed completely after 10 days' dressing change. Six weeks after the reconstruction surgery, callus formation was observed in the reconstructed thumb and the second toe of the donor foot of 10 patients, the Kirschner wires were removed; while callus formation of the reconstructed thumb was poor in 2 patients, and the Kirschner wires were removed after 2 weeks of delay. During the follow-up of 6 to 24 months, the shape of reconstructed thumb was similar to that of the healthy thumb, the discrimination distance between the two points of the reconstructed thumb was 7 to 11 mm, and the functional evaluation results were excellent in 4 cases, good in 6 cases, and fair in 2 cases. The interphalangeal joints of the hallux and the second toe of the donor foot were stiff, mild scar hyperplasia was left in the donor site of foot, and the standing and walking functions of the donor foot were not significantly limited. Conclusions: The application of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns adopts the concept of reconstruction instead of repair to close the wound. It can restore the shape and function of the damaged thumb without causing great damage to the donor foot.
Burns, Electric/surgery* ; Cicatrix/surgery* ; Free Tissue Flaps ; Hallux/surgery* ; Humans ; Hyperplasia ; Male ; Reconstructive Surgical Procedures/methods* ; Skin Transplantation/methods* ; Thumb/surgery* ; Toes/surgery* ; Treatment Outcome

Objective: To establish an intramedullary transplantation model of primary megakaryocytes to evaluate the platelet-producing capacity of megakaryocytes and explore the underlying regulatory mechanisms. Methods: Donor megakaryocytes from GFP-transgenic mice bone marrow were enriched by magnetic beads. The platelet-producing model was established by intramedullary injection to recipient mice that underwent half-lethal dose irradiation 1 week in advance. Donor-derived megakaryocytes and platelets were detected by immunofluorescence staining and flow cytometry. Results: The proportion of megakaryocytes in the enriched sample for transplantation was 40 to 50 times higher than that in conventional bone marrow. After intramedullary transplantation, donor-derived megakaryocytes successfully implanted in the medullary cavity of the recipient and produce platelets, which showed similar expression of surface markers and morphology to recipient-derived platelets. Conclusion: We successfully established an in vivo platelet-producing model of primary megakaryocytes using magnetic-bead enrichment and intramedullary injection, which objectively reflects the platelet-producing capacity of megakaryocytes in the bone marrow.
Animals ; Blood Platelets ; Bone Marrow ; Bone Marrow Cells ; Bone Marrow Transplantation ; Humans ; Megakaryocytes/metabolism* ; Mice