Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy. However, its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM). Here, we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate (CaCO₃) biomineralized Salmonella (Sal) as an in-situ cancer vaccine producer and systematical ITM regulator. CaCO₃ can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading, and such biomineralization did not affect the bioactivities of the bacteria. Upon intratumoral accumulation, the CaCO₃ shell was decomposed at an acidic microenvironment to attenuate tumor acidity, accompanied by the release of Sal and Ca²⁺/A23187. Specifically, Sal served as a cancer vaccine producer by inducing cancer cells' immunogenic cell death (ICD) and promoting the gap junction formation between tumor cells and dendritic cells (DCs) to promote antigen presentation. Ca²⁺, on the other hand, was internalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system, including DCs maturation, macrophages polarization, and T cells activation. As a result, such bio-vaccine achieved remarkable efficacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility. This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.

Objective:To analyze characteristics and trends of histopathological diagnosis of adult renal biopsy in Beijing from 2008 to 2020.Methods:A total of 4 652 cases of adult renal biopsy were collected from three hospitals in Beijing between 2008 and 2020. The patients were divided into three age groups: 18-40 years, 40-65 years and≥ 65 years; and also divided into three period: 2008-2011, 2012-2015, and 2016-2020. The pathological characteristics and changes of renal biopsy were analyzed in three age groups at different periods.Results:Among 4 652 cases primary glomerular disease accounted for 81.8%, the membranous nephropathy (MN, 32.4%, 1 509/4 652), IgA nephropathy (IgAN, 29.2%, 1 356/4 652) and minor glomerular abnormalities (MGA, 11.3%, 526/4 652) were the top three pathological types. The overall proportion of MN and diabetic nephropathy (DN) increased from 20.3% and 2.3% in 2008-2011 to 37.3% and 10.1% in 2016-2020) (χ2=99.9 and 96.1, both P<0.01), respectively. For age group 18-40 years, the MN and DN increased from 11.2% and 1.6% in 2008-2011 to 24.7% and 5.5% in 2016-2020 (χ2=32.7 and 20.7, both P<0.01), respectively. For age group 40-65 years the MN and DN increased from 26.6% and 3.2% in 2008-2011 to 41.5% and 13.1% in 2016-2020 (χ2=39.1 and 57.3, both P<0.01), respectively. For age group≥65 years the MN was the most common pathological type in the three periods, fluctuating between 41.3% and 55.0% (χ2=5.2, P=0.08); and DN increased from 0(0/63) in 2008-2011 to 7.5%(22/292) in 2016-2020 (χ2=8.1, P=0.02). Conclusion:The renal biopsy data show that membranous nephropathy and diabetic nephropathy are the most common primary and secondary adult glomerular diseases in Beijing recently.

Objective: To investigate the clinical effects of free superficial femoral artery femoral triangle perforator flap in the repair of skin and soft tissue defects in extremities. Methods: From January 2016 to November 2017, 14 patients (9 males and 5 females, aged 19 to 54 years) with skin and soft tissue defects in extremities accompanied with tendon and bone exposure were admitted to our unit. The size of skin and soft tissue defects after debridement ranged from 7 cm×3 cm to 10 cm×7 cm. The defects were repaired with free superficial femoral artery femoral triangle perforator flaps, with size ranging from 13.0 cm×2.0 cm to 20.0 cm×4.5 cm. The medial femoral cutaneous nerve was applied to the flap. The perforator flap was grafted onto the medial femoral cutaneous nerve in 6 patients. The donor sites were sutured directly. The survival of flaps and the follow-up of patients were observed. Results: All flaps of 14 patients survived successfully. The recipient sites and donor sites were healed completely in 13 patients, and 1 patient with partial skin necrosis at the edge of flap was healed after treatment. All patients were followed up for 6 months to 1 year after the operation. The flaps were in good shape, with nearly normal color and soft texture and no cicatrix contracture deformity. The flaps recovered protective sense in 6 patients who had medial femoral cutaneous nerve grafting, and the sensory recovery of the flap was slightly worse in the remaining 8 patients. There was no significant complications on the appearance and walking of the donor thigh in 14 patients, only a linear scar was left on the inner thigh, and no numbness was felt in the donor sites of patients. Conclusions The free superficial femoral artery femoral triangle perforator flap is an ideal therapy for repairing skin and soft tissue defects in extremities.

The target value of intact parathyroid hormone (iPTH) in main international guidelines is not consistent completely.Furthermore,the evidence levels of clinical studies these guidelines based on are generally low and most of them are based on observational studies.Some studies even showed that there was no association between iPTH level and clinical outcomes.This review focuses on the following three points for reassessing iPTH target value: comparison of iPTH target value in main international guidelines,the difference of iPTH target value in large clinical studies and reasons for the difference.

Objective To study the effect of quercetin on ADMA induced endoplasmic reticulum stress responses (ER stress).Methods Human umbilical veins endothelial cells (HUVECs) were cultured,and left untreated or challenged for 24h with 100μmol/L ADMA in the absence and presence of 20μmol/L quercetin,the PERK and IRE1 was determined by Western blot.ATF4 and CHOP mRNA was detected by RT-PCR.Cells apoptosis was detected by flow cytometry.Results ADMA induced HUVECs apoptosis.Quercetin inhibited ADMA-induced PERK and IRE1 protein expression and ATF4 and CHOP mRNA expression.At last,Quercetin inhibited ADMA-induced cells apoptosis.Conclusion ADMA induced ER stress and HUVECs apotosis while quercetin inhibited ADMA-induced ER stress and apoptosis.

Objective To observe the effects of tumor necrosis factor-or (TNF-α) and platelet derived growth factor (PDGF) on vascular neointimal hyperplasia on matrix metalloproteinase 9/2 gene knockout (MMP9/2-/-) mice and explore related mechanisms.Methods Mice of control group,MMP9-/-group,MMP2-/-group and MMP9/2-/-group were studied.Femoral artery was injured by transluminal wire,the mRNA expression levels of TNF-o and PDGF on femoral artery were detected by RT-PCR;the protein expression of MMP9 and MMP2 were assessed by Western blot on day 0,1,3,7,14and 28 post injury.Mice in control group received TNF-α(5 ng/ml,0.10 ml),TNF-α(0.05 ml) + MMP inhibitor SB-3CT (0.50 ng/ml,0.05 ml) injection,or PDGF-bb (10 ng/ml,0.10 ml) and PDGF-bb (0.05 ml) + SB-3CT(0.05 ml) injection around injured artery,intimal hyperplasia at 2 and 4 weeks after injury was observed.Intimal hyperplasia at 2 and 4 weeks after injury was also observed in MMP9/2-/-mice.TNF-α(5 ng/ml,0.10 ml) was injected to MMP2-/-mice,PDGF-bb (0.1 ml) was injected to MMP9-/-mice around injured artery,intimal hyperplasia at 2 and 4 weeks after injury was observed.The degree of neointimal hyperplasia were observed by the Elastica-van Gieson staining and the area of neointima and media of the arteries were measured by SigmaPlot and intima ratio was calculated.Vascular smooth muscle cell (VSMC) mediums of MMP9-/-and MMP2-/-mice were stimulated by TNF-α and PDGF-bb,respectively,and migration assay,and proliferation assay were performed,relative migration and proliferation cells numbers were counted.Results (1) mRNA expression of TNF-o (235.33 ± 23.68) and PDGF-bb (3.30 ±0.56) in femoral arteries peaked at 1 day after injury,while MMP9 or MMP2 protein expression peaked at 7 or 28 days after injury.(2) In control mice,TNF-α intervention significantly enhanced intimal hyperplasia at 2 weeks after injury (2.21 ±0.05 vs.1.55 ±0.03 in blank control group,P ＜ 0.05),while PDGF-bb intervention significantly enhanced intimal hyperplasia at 4 weeks after injury (2.60 ± 0.07 vs.1.89 ± 0.04,P =0.03).(3) Intima hyperplasia was significantly higher in control group than in MMP9/2-/-group at 2 weeks (1.63 ± 0.05 vs.0.46 ± 0.01,P =0.008) and 4 weeks (2.24 ±0.06 vs.0.51 ±0.01) after injury(P =0.005).(4) TNF-o intervention stimulated intimal hyperplasia in MMP2-/-mice (intimal ratio at 2 weeks after injury:1.73 ± 0.05 vs.1.23 ± 0.03,P =0.02) and PDGF-bb intervention stimulated intimal hyperplasia in MMP9-/-mice(intimal ratio at 4 weeks after injury:2.32 ± 0.06 vs.1.35 ± 0.03,P =0.03).(5) Reduced VSMC migration was evidenced in MMP9-/-mice post TNF-α stimulation (1.45 ±0.03 vs.2.16 ±0.04 in control group,P =0.03),while reduced VSMC proliferation post PDGF was seen in MMP2-/-group (1.15 ± 0.02 vs.1.82 ± 0.04 in control group,P =0.03).Conclusions TNF-o induced MMP9 activation plays a major role on promoting VSMC migration at the first 2 weeks after vascular injury,while PDGF induced MMP2 activation plays a crucial role on VSMC proliferation on the following 2 weeks after vascular injury in this mice model.Thus,the axis of TNF-α-MMP9-VSMC migration axis and PDGF-MMP2-VSMC proliferation axis are the two major working mechanisms responsible for intimal hyperplasia post vascular injury.

Objective To evaluate the effects on the mineral bone disorder using different calcium concentration citrate-based dialysate in maintenance hemodialysis (MHD) patients.To compare the concentrations of intact parathyroid hormone(PTH) with biointact PTH(1-84) in these patients.Methods Citrate dialysate with different calcium concentration (DCa 1.75,DCa 1.5,DCa 1.25 mmol/L)were used in turn in 15 stable MHD patients each week.Serum tCa and iCa were measured by automatic biochemistry analyzer.The concentrations of iPTH and bio-iPTH were compared.Results (1) The patients treated with DCa 1.75 citrate dialysate had increased serum iCa and tCa after dialysis,and PTH did not change significantly as compared to those findings before the dialysis.With the DCa 1.5 citrate dialysate,serum iCa and tCa were kept stable and PTH level was increased.With DCa 1.25 citrate dialysate,serum iCa and tCa decreased significantly and PTH decreased.(2)iPTH and bioPTH had excellent correlations.Variation of bio-iPTH was more correlated with the changes of calcium than iPTH.Conclusions Serum levels of iPTH,tCa and iCa can be kept stable in MHD patients treated with DCa 1.75 ～ 1.5 citrate dialysate.Bio-iPTH is a more sensitive marker for mineral bone disease than iPTH.

Objective To compare the effect of applying low molecular weight heparin calcium in different periods of reteplase for acute myocardial infarction(AMI).Methods Ninety-one cases of AMI were divided into group A(30 cases),group B(30 cases)and group C(31 cases)by random digits table.The patients in three groups were given reteplase intravenous thrombolysis,and 5000 U low molecular weight heparin calcium was abdominal wall subcutaneous injections once 12 h at intravenous thrombolysis immediately(group A),after intravenous thrombolysis 6 h(group B)and 12 h(group C).They all were treated for 7-10 d.The rate of coronary artery recanalization,acute phase complication and adverse reaction were compared among three groups.Results The rate of coronary artery recanalization in group A,B and C was 76.7％(23/30),96.7％(29/30),74.2％(23/31)respectively.The rate of coronary artery recanalization in group B was significantly higher than that in group A and C(P ＜ 0.05).The rate of acute phase complication and adverse reaction in group B[33.3％(10/30)]was significantly lower than that in group A and C[70.0％ (21/30)and 61.3％(19/31)](P ＜ 0.05).Conclusions After reteplase intravenous thrombolysis in 6 h,applying low molecular weight heparin calcium can significantly improve the rate of coronary artery recanalization and reduce the rate of acute phase complication and adverse reaction.

Objective To study the effect of long-term salmon calcitonin on bone mineral density (BMD), bone metabolism biochemical indicators and subjective score of bone pain in maintenance hemedialysis (MHD) patients with osteopenia. Methods Thirty-four MHD patients diagnosed as osteopenia by dual-energy X-ray absorptiometry (DXEA) were enrolled in this study. All the patients were treated with hypodermic injection of salmon calcitonin (50 U, thrice a week) for 12 months. The detecting parameters were as follows: BMD with DEXA in lumbar spine (L1-L4), femoral neck, troch, inter, and Ward's triangle before and after the study;serum bone metabolism biochemical indicators before and 6 and 12 months after the study;subjective scores of bone pain before and 1, 6, and 12 months after the study. Results Thirty-two patients were followed-up successfully. As compared to BMD parameters before study, the total T-score (-1.98± 2.20 vs 1.26±1.88, P=0.009) and total Z-score (-0.90±2.15 vs 0.08±2.05, P=0.002) of lumbar spine, the total T-score (-1.72±1.53 vs 1.06±1.58, P=0.016) and totle Z-score (-0.66±0.80 vs 0.08±1.08, P=0.029) of hip, the T-score of L3 (-2.02±2.51 vs 1.24±2.02, P=0.033), the Z-score of L2 (-0.44±1.82 vs 0.06±1.63, P=0.016), the Z-score of femoral troch (-0.65±1.11 vs 0.48±1.12, P=0.034) and the Z-score of inter (-0.58±0.94 vs 0.02±1.12, P=0.006) were increased significantly after study. But there were no significant differences in other examined regions and serum biochemical parameters. The subjective scores of bone pain were decreased rapidly for 41.7% after 1 month (P<0.01) and 76.6% after 6 months (P<0.01). The subjective score of bone pain after 12 months was similar to 6 months. The side effects of salmon calcitonin included nausea and vomitting in 5 cases (14.71%, 5/34), dizziness, blushing and flustered in 1 case respectively (3.13%,1/32). Conclusions Long-term hypodermic injection of salmon calcitonin can improve BMD and bone pain for MHD patients with osteopenia but has no significant effect on serum bone metabolism biochemical indicators. Salmon calcitonin is safe for MHD patients with seldom side effects, such as nausea and vomitting.

Citing the IT development of the General Hospital of Nanjing Military Region at Fuzhou as an example, the authors point out that emphasizing the role of the people and doing a good job of talent planning and cultivation is the key to the IT development of a hospital. They argue that a hospital must have leaders and managers that stress the IT development of the hospital; it must have a team of people with high IT expertise; it must have a large number of staff very familiar with the operation of the computer; and it must be able to integrate its human resources and give play to the overall efficiency.