Tumor-targeted therapy is a vital approach in precision medicine,selection of target molecule is a key element in tumor-targeted therapy.B7-H3(CD276),as an immune checkpoint molecule selectively highly expressed on tumor cells,is a crucial molecule involved in regulation of tumor immunity.Numerous recent studies have found that B7-H3,in addition to its immune check-point function,also participates in regulation of malignant biological behaviors of tumor cells and is considered to have great potential as a pan-cancer universal drug target.Current immunotherapeutic strategies targeting B7-H3 primarily include development of block-ing monoclonal antibodies(Blocking mAb),antibody-drug conjugate(ADC),chimeric antigen receptor(CAR)T/NK cell therapies,monoclonal antibody dependent cellular cytotoxicity(ADCC)drugs,radionuclide drug conjugates(RDC),bispecific/trispecific anti-body(BsAb/TriAb),and antibody cytokine drug combinations,among others.These strategies aim to enhance body's immune re-sponse to cancer through various mechanisms,thereby inhibiting tumor growth and metastasis.Multiple preclinical and clinical studies have shown that immunotherapy targeting B7-H3 has potential therapeutic value.Therefore,this article mainly reviews the latest status of development of tumor immunotherapy drugs targeting B7-H3 molecule.

Tumor-targeted therapy is a vital approach in precision medicine,selection of target molecule is a key element in tumor-targeted therapy.B7-H3(CD276),as an immune checkpoint molecule selectively highly expressed on tumor cells,is a crucial molecule involved in regulation of tumor immunity.Numerous recent studies have found that B7-H3,in addition to its immune check-point function,also participates in regulation of malignant biological behaviors of tumor cells and is considered to have great potential as a pan-cancer universal drug target.Current immunotherapeutic strategies targeting B7-H3 primarily include development of block-ing monoclonal antibodies(Blocking mAb),antibody-drug conjugate(ADC),chimeric antigen receptor(CAR)T/NK cell therapies,monoclonal antibody dependent cellular cytotoxicity(ADCC)drugs,radionuclide drug conjugates(RDC),bispecific/trispecific anti-body(BsAb/TriAb),and antibody cytokine drug combinations,among others.These strategies aim to enhance body's immune re-sponse to cancer through various mechanisms,thereby inhibiting tumor growth and metastasis.Multiple preclinical and clinical studies have shown that immunotherapy targeting B7-H3 has potential therapeutic value.Therefore,this article mainly reviews the latest status of development of tumor immunotherapy drugs targeting B7-H3 molecule.

Objective To evaluate the diffusion distribution of bone cement in the vertebral body by quadrant method,and to analyze and evaluate the correlation between the diffusion distribution type of bone cement and new vertebral fractures after vertebral augmentation.Methods A total of 170 subjects who met the conditions from January 2020 to December 2021 were collected.According to the anteroposterior and lateral view of the spine,the injured vertebra was divided into four quadrants,and divided into homogeneous diffusion group and uneven diffusion group according to the postoperative diffusion distribution of bone cement in the injured vertebra.The incidence and types of refracture were followed up,and the VAS score and Cobb angle were compared between the two groups.Results 170 patients were followed up for at least 12 months,including 90 patients in homogeneous diffusion group and 80 patients in heterogeneous diffusion group.There were 33 cases of refracture(19.41％),12 cases of refracture(13.33％)in the diffuse homogeneous group,and 21 cases of refracture(26.25％)in the diffuse heterogeneous group,and the difference between the groups was statistically significant(P＜0.05).The site of refracture in the diffuse homogeneous group was mainly the clinical vertebral fracture,while the probability of refracture in the diffuse heterogeneous clinical vertebra and the operated vertebra was similar.The incidence of postoperative bone cement leakage in the diffuse homogeneous group was significantly lower than that in diffuse heterogeneous group(P＜0.05).The VAS score and Cobb angle were significantly improved in both groups after surgery and at the last follow-up compared with those before surgery,but there was no significant difference between groups.Conclusion The incidence of new vertebral fractures after vertebroplasty is closely related to the type of cement diffusion,and the risk of refracture defined as uneven cement diffusion by quadrant method is high.

Objective:To investigate the therapeutic effect of anterolateral thigh Flow-through flap transfer surgery combined with Masquelet technique in reconstruction of Gustilo IIIC open fractures of distal tibia.Methods:Between July 2017 and May 2021, 7 patients who had Gustilo IIIC injuries in the lower limb were treated in the Department of Orthopaedics Surgery, Wuxi 9th People's Hospital by emergency surgery with transfer of anterolateral thigh Flow-through flap combined with Masquelet technique. The patients were 5 males and 2 females, aged 36 to 63 (50.0±10.4) years old. Size of soft tissue defects was 11 cm × 4 cm to 23 cm × 7 cm, the length of bone defects was 3.5-7.5 (5.34±1.52) cm and the bridging length for vascular defects was 7-12 (9.21 ± 2.34) cm. The size of the flaps was 12 cm × 5 cm - 24 cm × 8 cm. All patients received postoperative follow-up at the outpatient clinic and complications of wound, fracture healing and the recovery of limb function were observed.Results:All flaps survived uneventfully and successful limb salvage were achieved in all 7 patients, together with all bone grafts healed without infection. The follow-up lasted for 12-38 (26.69±10.73) months. At the last follow-up, the appearance and functional recovery of the lower limbs were satisfactorily. The function of ankle was evaluated according to American Orthopedic Foot and Ankle Society (AOFAS) : 3 patients in excellent, 3 in good and 1 in fair.Conclusion:Emergency anterolateral thigh Flow-through flap transfer surgery with Masquelet technique is a safe, effective and feasible surgical procedure for Gustilo IIIC open fractures of distal tibia. It allows to close the wound and rebuild the blood supply in distal limb in the primary or emergency surgery, and allows to perform bone grafting and internal fixation in stage-II surgery. The patients benefit from high rate of success in limb salvage and good function recovery of the affected limb.

Digestival functional surgery refers to surgical treatment for patients with functional diseases of the digestive tract. With the continuous development of minimally invasive surgery, most of surgical procedures for digestive functional diseases have been conducted by minimal invasive approach. Based on decades of clinical practice, the authors focus on minimally invasive surgeries for a group of digestive functional diseases such as achalasia of cardia, gastroesophageal reflux disease, volvulus of stomach, gastroptosis, dolichocolon, refractory constipation, rectocele and rectal prolapse, and make ageneral summary on current status and prospects of its clinical application combined with literatures.

Objective To explore the condition of cortistatin (CST)expression in human renal tissue and the changes in the level of CST in IgA nephropathy (IgAN)of different degrees.Methods Ten tumor adjacent normal renal tissue samples were collected.The mRNA and protein expressions of CST in human renal tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR)and Western blotting,respectively.Immunohistochemisty (IHC)was performed to locate the expression of CST in renal tissue.According to the grading system of Lee et al,IgAN was divided into three groups:grade Ⅰ -Ⅱ (group A),grade Ⅲ -Ⅳ (group B),and grade Ⅴ (group C),and ten renal biopsy tissue samples were collected for each group.IHC was performed to detect the change in the level of CST in normal and IgAN renal tissue of different degrees.The effect of clinical indices on the level of CST in IgAN renal tissue was assessed by multiple linear regression analysis.Results RT-PCR and Western blotting showed that CST was expressed in renal tissue and IHC showed that CST was expressed on renal tubular epithelial cells.In IgAN,the higher the pathological grade was, the higher the expression of CST in renal tubules was.Multiple linear regression analysis showed that the pathological grade was associated with the expression of CST in renal tissue (r =0.875,P <0.01).Conclusion CST may participate in the inflammatory reaction of IgAN pathological injury and exert anti-inflammation effects.

BACKGROUNDIn China, the prevalence of chronic kidney disease has increased significantly. Many studies shows that the spectrum of kidney disease had changed in recent years. We retrospectively analyzed the pathological types of renal biopsy and its spectrum change at the General Hospital of the Chinese People's Liberation Army from December 1987 to December 2012, in order to offer new supporting evidences for further specifying the distribution of renal pathological types in China.

METHODSAccording to the "Revised Protocol for the Histological Typing of Glomerulopathy" (WHO, 1995), pathological diagnosis of renal biopsy was classified, detection rate of each pathological type was summarized (i.e., percentage of total renal biopsy cases), study period was divided at an interval of 5 years, and age-stratified distribution change of main pathological types was analyzed.

RESULTSThe proportion of pathological types in 11 618 cases of renal biopsy was as follows: primary glomerulonephritis (PGN, 70.7%), secondary glomerulonephritis (SGN, 20.7%), tubular-interstitial nephropathy (4.0%), hereditary/rare nephropathy (0.3%), end-stage renal disease (0.9%), and unclassified renal disease (3.3%). Among PGN, there was IgA nephropathy (IgAN, 37.0%), membranous nephropathy (MN, 11.8%), mesangial proliferative glomerulonephritis (MsPGN, 8.9%), minimal change disease (MCD, 6.6%), and focal segmental glomerulosclerosis (3.9%). Among SGN there was lupus nephritis (LN, 5.5%), Henoch-Schönlein purpura glomerulonephritis (5.3%), hepatitis B virus-associated nephritis (HBVAN, 3.03%), diabetic nephropathy (2.2%), and hypertension/malignant hypertension-associated renal damage (1.9%). Pathological data were analyzed from 1987-1992 to 2008-2012 (after age adjustment). Detection rate of IgAN tended to rise (P < 0.001). Detection rates of MN and MCD rose significantly (P < 0.001), but detection rate of MsPGN dropped significantly (P < 0.001). Among SGN, detection rate of HBVAN tended to drop (P < 0.001).

CONCLUSIONIn China, PGN was the most common glomerulopathy (mostly IgAN), LN was the most common SGN, and detection rate of MN and MCD rose significantly.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; methods ; Child ; Child, Preschool ; China ; Female ; Glomerulonephritis, Membranous ; diagnosis ; Humans ; Kidney ; pathology ; Kidney Diseases ; diagnosis ; Male ; Middle Aged ; Young Adult

Objective To describe the expressions of programmed death-1 (PD-1) and its ligand PD-L1 on the surface of peripheral blood lymphocytes in patients with tuberculosis.Methods A total of 77 cases of pulmonary tuberculosis were recruited,of which 27 were single infection,41 were coincident with bacterial or fungal infection and 9 patients with diabetes mellitus.Twenty-nine healthy donors were also enrolled as control group.The expressions of PD-1/PD-L1 on the peripheral blood lymphocytes and mononuclear cells were detected using immunostaining and flow cytometry.Collected data were analyzed with t-test statistics.Results Among the three groups of tuberculosis including pulmonary tuberculosis,pulmonary tuberculosis coincident with infection and pulmonary tuberculosis with diabetes mellitus,the percentages of CD4+ CD25+ T cells as well as CD4+ CD25high T cell subsets were both significantly higher than those in healthy controls (t=4.892,4.635,4.974,5.407,4.660,5.279,all P＜0.01).The expression of PD-1 was up regulated on the surface of CD8+ T cells in the groups of tuberculosis as compared with the control group (t=6.392,8.249,7.072,all P＜0.01).The proportions of PD-L1 expressed on the monocytes in each group were (42.51 ± 7.54) ％,(49.42± 6.29) ％ and (48.46 ± 14.58)％,respectively.The difference was significant in contrast to the control group,which was (17.91 ±3.03)％ (t=5.168,6.854,5.665,all P＜0.01).PD-L1 expression was also up-regulated on B cells in each group and much higher than that of the control group (51.51±7.32)％,(50.85±7.09)％,(55.66±14.29)％ vs (40.11±4.25)％ (t=2.562,2.046,2.766,all P＜0.05).Conclusion PD-1/ PD-L1 co-inhibitory pathway could be closely related to the development of tuberculosis and its complications,which is involved in the attenuation of anti-tuberculosis and anti infection immune responses.

Background Corneal neovascularization (CNV) is one of the causes of corneal blindness.Studies showed that zonula occludens-1 (ZO-1) can inhibit pathological angiogenesis through physical barrier formed by tight junction structure.However,whether ZO-1 plays a role in CNV is unclear.Objective The aim of this study was to explore the effect of ZO-1,a tight junction protein on experimental CNV.Methods The CNV models were established in the left eyes of 24 clear male BALB/c mice aged 7-8 weeks by putting NaOH filter paper in the center of corneas for 15 seconds (15 s group) or 40 seconds (40 s group).CNV was examined and evaluated under the slit lamp microscope,and the expression of ZO-1 mRNA in the corneas were detected and compared by reverse transcription PCR (RT-PCR) between the two groups 2 weeks after modeling.In addition,54 models created by the same method were assigned to 3 groups according to randomized number table,0.2％ hyaluronic acid (HA),antiZO-1 neutralizing antibody (10 mg/L) +0.2％ HA and mouse hypoxia inducible factor-1α (HIF-1α) recombinant protein (5 mg/L)+0.2％ HA were topically administrated in the mice three times a day for 1 week after modeling respectively.The corneas were extracted 2 weeks after application of the drugs.Expression of CD31 in the CNV was assayed to calculate the number and the area of CNV by immunohistochemistry.The expression of VEGF mRNA in the corneas was detected by RT-PCR.The percentages of macrophage-specific F4/80 positive cells and neutrophilsspecific Ly-6G positive cells were calculated to evaluate the infiltrations of inflammatory cells in the corneas by flow cytometry.Results In 2 weeks after alkali burn of corneas,the number of severe CNV was more in the 40 s group than that in the 15 s group (x2 =6.032,P=0.049),and the expression level of ZO-1 mRNA was lower in the 40 s group than that in the 15 s group (1.15±0.08 versus 1.53±0.04) (t=4.157,P=0.014).CD31 positive cell number was more and the staining area was larger in the ZO-1 antibody group and HIF-1α positive control group than those in the 0.2％ HA group (cells:t=-129.590,-226.820,both at P=0.000;area:t =-5.310,-8.840,both at P=0.000).The relative expressions level of vascular endothelial growth factor (VEGF) mRNA was 1.33±0.10 and 1.46±0.11 in the ZO-1 antibody group and HIF-1 α positive control group respectively,which were significantly higher than 0.93±0.06 of the 0.2％ HA group (t =-5.820,-7.284,both at P =0.000).The percentages of positive cells in the ZO-1 antibody group and HIF-1α positive control group were significantly increased in comparison with the 0.2％ HA group for F4/80 (t =-16.750,-17.480,both at P =0.000) and for Ly-6G (t =-21.450,-27.680,both at P=0.000).Conclusions Alkali burn induced CNV downregulates the expression of ZO-1 mRNA.Administration of ZO-1 antibody causes the rise of VEGF mRNA in CNV and the infiltration inflammation cells,which suggests that the influence of ZO-1 on CNV is associated with the expression of VEGF.

OBJECTIVETo investigate high-concentration uric acid-induced endothelial dysfunction mediated by miR-155.

METHODSHuman umbilical vein endothelial cells (HUVECs) were incubated with 600 µmol/L uric acid for 24 and 48 h, and eNOS expression and NO content in the cell culture were measured. The target genes of miR-155 were predicted using on-line analysis software and validated by dual-luciferase system. Real-time PCR was used to detect the expression of miR-155 in endothelial cells incubated with high-concentration uric acid. The effect of miR-155 on endothelial dysfunction was assessed by transfection of its inhibitor into HUVECs.

RESULTSThe expression of eNOS and NO secretion decreased obviously in HUVECs incubated with 600 µmol/L uric acid. MicroRNA on-line analysis software and dual luciferase reporter experiments suggested that the level of eNOS translation was directly regulated by miR-155. The expression of miR-155 in endothelial cells was upregulated after stimulation with high-concentration uric acid, and was inhibited by transfection of miR-155 inhibitor. Expression of eNOS and secretion of NO were elevated in endothelial cells transfected with miR-155 inhibitor after incubation with high-concentration uric acid.

CONCLUSIONHigh-concentration uric acid can down-regulate eNOS expression via miR-155 to induce endothelial dysfunction.

Cells, Cultured ; Down-Regulation ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Hyperuricemia ; metabolism ; pathology ; MicroRNAs ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Uric Acid ; blood