B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

Objective To investigate the protective effect of mitochondrial fission inhibitor 1(Mdivi-1),on organ function in rats with explosive blast injury combined with hemorrhagic shock.Methods A total of 192 SD rats(half male and half female,12 weeks old,weighing about 220 g)were randomly divided into 6 groups:Sham group(only surgical incision along the midline of the abdomen),model group(ESH group,thermal radiation and shock wave injury followed by femoral artery hemorrhage),lactated Ringer's solution resuscitation group(ESH+LR group,LR solution infusion in the femoral vein for resuscitation),and low-,middle-and high-dose Mdivi-1 groups(0.1,0.5 and 1.0 mg/kg Mdivi-1 intervention after infusion of LR solution).Fluorescent protein tracing was used to determine the leakage amount of fluorescent protein in the lung and kidney tissues to evaluate the vascular permeability.Evans blue dye staining was employed to observe the intestinal permeability and pulmonary vascular permeability.Laser Doppler flowmetry was applied to monitor the tissue blood perfusion in the liver,kidneys,and intestine.Serum levels of cardiac injury marker troponin I(TNI),liver function markers aspartate aminotransferase(AST)and alanine aminotransferase(ALT),and renal function markers serum creatinine(Scr)and blood urea nitrogen(BUN)were detected to evaluate the functions of corresponding organs.The water contents of the lungs and brain were calculated by measuring wet weight and dry weight of the lung and brain tissues.Blood pressure,heart rate,and respiratory rate were monitored.The survival time and 72-hour survival rate were recorded and calculated.Results Compared with the Sham group,the ESH group exhibited significantly increased vascular permeability in the lungs and kidneys as well as intestinal tissue(P<0.05),along with obviously elevated water contents in the lungs and brain(P<0.05),and decreased blood perfusion in the liver,kidneys,and intestine by 57.1%,39.2%,and 43.2%of the Sham group,respectively(P<0.05),elevated levels of TNI,AST,ALT,Scr and BUN(P<0.05),mean survival time of 3.8±1.1 h,and a 72-hour survival rate of 0(P<0.05).Although LR solution resuscitation reduced vascular permeability and alleviated organ injury in rats with explosive injury combined with hemorrhagic shock,there were no significant differences compared to the ESH group(P>0.05).Mdivi-1 treatment notably decreased vascular permeability in the lungs and kidneys and intestine,and water contents in the lungs and brain when compared with the LR group(P<0.05),with the dose of 0.5 mg/kg demonstrating the most significant effect.Additionally,Mdivi-1 treatment also significantly enhanced organ perfusion,improved organ functions,prolonged survival time,and increased survival rate.The 0.5 mg/kg treatment resulted in a 72-hour average survival time 55.64 h and a survival rate of 62.5%.Conclusion Mitochondrial fission inhibitor Mdivi-1 can reduce the permeabilities in the lungs,kidneys and intestine,improve tissue blood perfusion,protect the organ functions of the heart,liver and kidneys,and finally prolong survival time and increase survival rate in rats with concomitant explosive blast injury and hemorrhagic shock.

Objective: To explore the treatment options for congenitally missing teeth in patients with ectodermal dysplasia and provide a clinical reference. Methods: A patient with ectodermal dysplasia with a concave midface, anterior protrusion of the chin, and underdevelopment of the lower third of the face presented with congenital loss of multiple maxillary teeth, malocclusion of the remaining teeth, congenital loss of mandibular dentition, small dental arches, and upper and lower alveolar bone hypoplasia. The patient was treated by means of a removable partial maxillary prosthesis, implants in the anterior region of the lower mandible designed with the assistance of digital guides, and bar-clamped implant-overlay prostheses. A literature review of the protocol for the treatment of this condition was also conducted. Results: In addition to good retention and stability after denture wear, an excellent occlusal relationship, improvement of the patient's facial appearance, including upper and lower lip fullness, more equal balancing of the lower and middle 1/3 of the face, and improved masticatory function were achieved. The results of the literature review showed that patients with ectodermal dysplasia who are congenitally edentulous usually have a complex intraoral situation that makes restoration difficult, and common restorative modalities for these patients include fixed bridges, removable partial dentures, complete dentures, overdentures, and implant prostheses, which need to be selected according to the actual intraoral situation of each patient. Currently, there is no consensus on the treatment of congenitally missing teeth in patients with ectodermal dysplasia, and some scholars have suggested that fixed restorations be recommended for patients with fewer missing teeth, while the option of removable or implant-covered denture restorations should be given to patients with more missing teeth, with removeable prostheses for underage patients that are replaced with permanent fixed prostheses when the jaws have stabilized. Conclusion In patients with ectodermal dysplasia with congenital tooth loss, all factors should be taken into account, and an individualized restorative plan should be developed.

BACKGROUND:Osteoporosis is often accompanied by sarcopenia and an increased risk of fractures from falls.Recent studies have indicated a close relationship between lipid metabolism and sarcopenia.Abnormal lipid metabolism may directly impact muscle physiological function and metabolism. OBJECTIVE:To investigate the relationship between lipid metabolism and sarcopenia and evaluate their causal relationship using Mendelian randomization. METHODS:Mendelian randomization was used to explore the causal relationship between low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,triglycerides,and muscle mass.Research data from genome-wide association studies were used and a sensitivity analysis was conducted to verify the reliability of the results.Approximate indicators of muscle mass,including trunk lean mass and appendicular lean mass,were used as outcome measures. RESULTS AND CONCLUSION:The study found a negative correlation of low-density lipoprotein cholesterol and triglycerides with muscle mass,while no correlation was observed between high-density lipoprotein cholesterol and muscle mass.The results of the sensitivity analysis indicated a robust causal relationship.Using Mendelian randomization,this study provides evidence of a causal relationship between low-density lipoprotein cholesterol and triglycerides and muscle mass.This finding deepens our understanding of the effects of lipids on sarcopenia and has important clinical implications for the prevention and treatment of sarcopenia and osteoporosis.

Online teaching become the major teaching method for international students,how to adjust and optimize the online teaching mode,and explore a new teaching method suitable for international students has become an urgent problem for international students'education.According to the characteristics of the strong independent learning ability of international students,also paying attention to the impact of the time difference on the teaching quality,we adjusts and transforms the course content and teaching mode in this teaching reform,and the mode of teacher-lecturing+students'self-study+teacher-student discussion and feedback is adopted to study and practice the online teaching of Medical Immunology course.This teaching reform has fully activated the drive of international students'learning,and made international students get the ability of lifelong learning.At the same time,through the reasonable arrangement of teaching content and learning mode,the time difference existing in the teaching process of international students is well resolved,makes up for the poor effect of online lectures,and achieves good teaching effect.

In order to understand the difference and expression of genes in CEK cells before and af-ter baicalin interferes with IBV,further reveal and analyze the mechanism of baicalin interfering IBV replication in CEK cells in vitro.After IBV infected CEK cells for 2 h,9.75 mg/L baicalin liq-uid was added to interfere with CEK cells,which was recorded as the baicalin(H-IBV)group,and three replicate wells were set in the control group and the IBV(IBV)infection group.After 36 h culture,cell samples were collected and subject to transcriptome for sequencing.The results showed that there were 102 differentially expressed genes in H-IBV group compared with IBV in-fection group,among which 48 genes weresignificantly up-regulated and 54 genes were significantly down-regulated.Through functional annotation in GO and KEGG databases,it was found that dif-ferentially expressed genes were mainly annotated in biological processes such as cellular proces-ses,biological regulation,metabolism,and secondary pathways such as viral infectious diseases,signal transduction and interaction.Retinol metabolism pathway,phospholipid transfer to mem-brane,IL-27 mediated signaling pathway,MDA5/RIG-I and Toll-like receptor signaling pathway were significantly enriched in CEK cells,and the production of type Ⅰ interferon and interferon al-pha and the process of antiviral infection were also positively regulated.There were more differen-tial genes enriched in nucleic acid catalysis,immune system,and reaction,and interbiological reac-tion.Through the STRING network interaction map,it was found that most immune-related genes could form a 36-node interaction network centered on IRF7,TLR3 and STAT1.Therefore,com-pared with IBV group,the differentially expressed genes after baicalin treatment were mainly an-notated and enriched in the biological process,and the immune system and response were en-hanced,mainly through the positive regulation of IRF7 in the MDA5/RIG-I receptor signaling pathway and the inhibition of TLR3 signal transduction in the Toll-like receptor signaling path-way.Positive regulation of IL-27 mediated pathway and regulation of JAK-STAT signaling path-way were supplemented by activation of the expression of IRF7,TLR3,STAT1 and other related genes,and interaction with corresponding downstream proteins to promote the expression of IFN-α and regulatory cytokines,coupled with negative regulation of viral(defense)response and viral processes.Thus,baicalin interferes with IBV replication in CEK cells.

Objective To investigate the changes in brain dynamic functional connectivity(dFC)in children and adolescents with idiopathic generalized epilepsy(IGE)who have negative findings for conventional magnetic resonance imaging(MRI)and to explore the correlation between dFC indicators and clinical variables.Methods A total of 40 children and adolescents with IGE who have negative findings for routine brain MRI and 37 healthy controls were enrolled.T2-fluid attenuated inversion recovery(T2-FLAIR)was performed for all subjects.They also uinderwent 3-dimensional T,weighted imaging(3D-T1WI)and resting-state functional MRI(rs-fMRI).Using independent component analysis(ICA),sliding time windows,and k-means clustering,we identified 6 functional connectivity states and derived dFC indicators,including fraction of time,mean dwell time,and the number of transitions.Then,SPSS18.0 and GIFT software Stats module were used to analyze the intergroup differences in dFC and its correlation with clinical variables.The reliability and stability of the dFC results were validated by changing the size of the sliding window.Results There were no significant differences in the general clinical data between the IGE group and the control group(P＞0.05).Compared with the control group,the IGE group showed in state 5 increased dFC within the default mode network(DMN),increased dFC between DMN and the frontoparietal network(FPN),and decreased dFC between DMN and the visual network(VN)(P＜0.001).In state 6,the IGE group showed increased dFC between DMN and VN,increased dFC between the basal ganglia network(BGN)and the sensorimotor network(SMN),decreased dFC between the DMN and the attention network(ATTN),and decreased dFC within the VN(P＜0.001).There were statistically significant differences between the two groups in the fraction of time(Z=-2.192,P=0.028)and the mean dwell time(Z=-2.144,P=0.032)in state 1,in the fraction of time(Z=-2.444,P=0.015)and the mean dwell time(Z=-2.368,P=0.018)in state 4,and in the fraction of time(Z=-2.047,P=0.041)in state 6.There was a negative correlation between the duration of the disease and the fraction of time of state 1 in the IGE group(r=-0.421,P=0.007,Bonferroni correction).In the validation analysis,significant differences in dFC indicators between the IGE group and the control group persisted when the size of the sliding window and the number of clusters were changed.Conclusion Children and adolescents with IGE and negative findings for conventional MRI exhibit abnormal dynamic properties of whole-brain functional connectivity,and the fraction of time of state 1 in IGE patients is correlated with clinical variables,providing new imaging evidence for research in the neural mechanisms of children and adolescents with IGE.

Objective : To evaluate the effect of anatomical healing abutments for mandibular first molars on the morphological changes of gingival soft tissue after implant restoration, as well as on peri-implant gingival molding, food ingrowth and patient satisfaction, to provide a basis for clinical selection. Methods : Twenty-six patients who received implant restoration for a single missing mandibular first molar between September 2020 and September 2021 at the Oral Implant Center of Changsha Stomatological Hospital were randomly divided into a control group (13 cases with 14 implants) and a trial group (13 cases with 14 implants), of which 12 were male and 14 were female; the trial group had anatomical healing abutments applied for 4 weeks and then underwent crown restoration, while the control group finished five time points (before the second stage surgery, 4 weeks after the second stage surgery, immediately after the crown restoration, 4 weeks after the crown restoration, and 12 weeks after the crown restoration). A 3Shape intraoral scanner was used to scan the jaw before and 4 weeks after the second stage surgery to quantify the soft tissue changes and compare the effect of the healing abutment on gingival molding between the two groups. The incidence of food impaction was recorded and compared between the two groups at 4 weeks and 12 weeks after crown restoration. Patient satisfaction was recorded and compared between the two groups immediately after crown restoration, 4 weeks after crown restoration and 12 weeks after crown restoration Results : Four weeks after implant surgery, it was observed that the gingival proximal and distal gingival papillae increased on the coronal side in the test group compared to the control group, 0.50 (0.26, 0.72) mm in the near-medium test group and 0.27 (0.24, 0.38) mm in the control group, with a statistically significant difference (P = 0.029), and 0.48 (0.26, 0.62) mm in the far-medium test group and 0.23 (0.13, 0.39) mm in the control group, with a statistically significant difference (P = 0.004). There was no statistically significant difference (P>0.05) in the buccolingual to gingival margin apex to coronal molding or in the buccolingual to lingual soft tissue at 0, 1, or 2 mm of the root of the middle 1/3 apex of the buccal and lingual gingival margins between the two groups. Compared to the control group, there was no statistically significant difference in the incidence of food impaction observed 4 weeks and 12 weeks after crown restoration in the test group (P>0.05). The satisfaction scores were higher in the trial group than in the control group immediately, 4 weeks, and 12 weeks after crown restoration, and the difference between the groups was statistically significant (P < 0.05). Conclusion The anatomical healing abutment for the implant mandibular first molar was superior to the finished healing abutment in terms of soft tissue contouring with an increase in the coronal aspect of the proximal and distal gingival papillae, resulting in high patient satisfaction.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.