Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To explore the mechanism of anti anxiety (AD) effect of Shenqi Schisandra chinensis using network pharmacology and molecular docking technology.Methods:The main active ingredients of S-Q-W-W-Z (Shenqi Schisandra chinensis) were screened through the TCMSP database. The corresponding targets of the active ingredients were obtained through the TCMSP database and SymMap database. The drug active ingredient target relationship network was visualized using Cytoscape. Utilize TTD, OMIM, NCBI, Drugbank, and GeneCards databases to directly identify potential targets for anxiety. We constructed interaction diagrams of potential targets based on the String database, and used Cytoscape tool to obtain key target proteins. Gene ontology (GO) enrichment analysis and Tokyo Encyclopedia of Genomes (KEGG) signaling pathway analysis were used to identify key targets and signaling pathways for anti anxiety effects of Schisandra chinensis. AutodockTools software was used to perform molecular docking on key active ingredients and key target proteins, and their binding energies were calculated. The molecular docking results were visualized using PyMol software.Results:The 63 effective ingredients in Shen-Qi-Wu-Wei-Zi (Shenqi Schisandra chinensis) can act on anxiety disorder through 69 targets. Among them, quercetin, luteolin, and stigmasterol are the main active ingredients, and serine threonine protein kinase 1 (AKT1) protein and interleukin-6 (IL-6) protein are key target proteins. Molecular docking technology has verified the good binding ability between these key active ingredients and key target proteins. Shenqi Schisandra mainly exerted therapeutic effects on anxiety disorders by regulating Toll like receptor signaling pathways, tumor necrosis factor (TNF) signaling pathways, cancer pathways, and other pathways.Conclusions:The Shenqi Schisandra may exert anti anxiety effects by regulating related targets such as AKT1 and IL-6, regulating inflammatory reactions, cell apoptosis, and other processes.

OBJECTIVEOsseointegration of orthodontic microscrew implant is influenced by tooth extraction. This study aims to evaluate the safety margin of the osseointegration of orthodontic implants by investigating the healing process of the implant-bone interface through histopathological studies and quantitative determination.

METHODSTwelve male beagles were selected and randomly divided into four groups. An orthodontic microscrew was implanted beside the tooth extraction area. Animals were killed in 1, 3, 8, and, 12 weeks to investigate tissue response. Histomorphological observation and bone implant contact ratio (BIC) tests were performed at different healing time after implantation.

RESULTSA new bone was formed on the implant-bone interface of the control group. Bone resorptions were also detected in the experimental group 3 weeks after implantation. The BIC level of the control groups increased during the first 8 weeks; no change was observed anymore after the 8th week. On the other hand, the BIC value in the experimental group decreased in the first 3 weeks. It then increased rapidly and reached its peak of 80.08% in the 8th week. No significant difference wa s found between the experimental and control groups in the first 3 weeks. After the 3rd week, the BIC value of the experimental group (44.35%) was lower than that of the control group (55.46%) (P < 0.01).

CONCLUSIONThe healing process after implantation was influenced by tooth extraction. Bone resorption was detected at an early stage. However, vigorous bone remodeling was observed subsequently.

Animals ; Bone Remodeling ; Bone and Bones ; Dental Implantation, Endosseous ; Dental Implants ; Dogs ; Male ; Mandible ; Osseointegration ; Prostheses and Implants ; Tooth Extraction ; Wound Healing

Objectives To explore the effect of transient continuous subcutaneous insulin infusion (CSII) on β cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetic patients and its potential mechanism. Methods Ten patients with newly diagnosed type 2 diabetes mellitus (T2DM) accepted CSII for two weeks. Intravenous glucose tolerance test (IVGTT) and hyperinsulinemia euglycemia clamp test were performed before and after CSII. Serum soluble E-selectin (sE-selectin) was used to evaluate the injury of vascular endothelial cell, while serum high sensitivity C reactive protein (hsCRP) and soluble CD_(14) (sCD_(14)) were both used to assess inflammatory condition. Results (1) Compared with those before treatment, the blood glucose levels of IVGTT, the area under the curve of the blood glucose, glycosylated hemoglobin, TC and LDL-C in the patients were decreased after CSII (P < 0. 05 or 0. 01). (2) Compared with those before treatment, the insulin levels of IVGTT (except the fasting insulin), the area under the curve of insulin and acute insulin response were all increased after CSII(P < 0.05 or 0.01). (3) Compared with that before treatment, the glucose infusion ratio in the clamp test [(3.46±1.66)mg·kg~(-1)·min~(-1) increased to (7.14±2.37)mg·kg~(-1)·min~(-1)]and HOMA-β elevated, while HOMA-IR declined (P <0. 05 or 0. 01 in all). (4) Compared with those before treatment, the levels of serum sE-selectin, sCD_(14) and hsCRP were decreased (P < 0. 01, except for hsCRP) . Conclusion Transient intensive insulin therapy in patients with newly diagnosed T2DM is useful to restore 13 cell function, attenuate insulin resistance, repair vascular endothelial injury and improve the disorder of blood sugar and lipid. The mechanism may be related with the inhibition of inflammation in patients.

OBJECTIVE: To examine the influence of exogenous fat (lard) on the bone mineral density (BMD) of lumbar spine measured by dual energy X-ray absorptiometer (DXA) Hologic QDR 4500A in different sites in healthy women. METHODS: Lard packets (5 cm or 10 cm thick) were prepared. The lumbar spine (LS) DXA scans were performed on 37 women(Group A), who were repeated with lard packets (5 cm or 10 cm thick) placed over the abdomen, and the hip DXA scans were performed on 18 women(Group B), who were repeated with lard packets (5 cm or 10 cm thick) placed over the left thigh. Whole body DXA scans were performed on 8 women(Group C), who were repeated with 5 cm thick lard packets over the abdomen. The pair t-test was used to compare the value of BMD with and without lard. RESULTS: After lard was placed over abdomen, the bone area (BA), bone mineral content (BMC), and BMD of the LS decreased significantly (P<0.001);at the hip, BA had no significant change, but the BMC and BMD of the neck, trochanter, and inter trochanter increased significantly (P<0.01~0.05). The BMD of the whole body had no significant change (P>0.05). CONCLUSION Lard impacted the BMD by DXA Hologic QDR 4500A, BMD of the LS significantly decreases, but BMD of the whole body has no significant change. BMD of the hip significantly increases with lard.
Absorptiometry, Photon ; Adiposity ; physiology ; Adult ; Aged ; Bone Density ; Female ; Humans ; Lumbosacral Region ; diagnostic imaging ; Middle Aged ; Phantoms, Imaging

OBJECTIVE: To observe the effect of exogenous fat on the bone mineral density (BMD) of lumbar spine (LS) on a phantom measured by dual energy X-ray absorptiometry (DXA) Hologic QDR4500A. METHODS: LS DXA scans were performed on an LS phantom, and were repeated when with lard packets (2 fresh lard packets and 2 refined lard packets, 5 cm or 10 cm thick). RESULTS: After fresh lard packets were placed, only L1 BMD decreased significantly (P<0.05).When the 5 cm-thick refined lard packet was placed, BMD, bone mineral content (BMC),and bone area (BA) decreased obviously, but with the 10 cm-thick refined lard packet, BMD, BMC and BA decreased significantly (P<0.05 or P<0.01). CONCLUSION The exogenous fat may affect LS BMD of lumbar spine phantom by DXA Hologic QDR4500A, with significant decrease of the value,which may cause anomaly measurement of BMD in obese people and even misdiagnosis of osteoporosis.
Absorptiometry, Photon ; Adipose Tissue ; diagnostic imaging ; Body Composition ; Bone Density ; Humans ; Lumbar Vertebrae ; anatomy & histology ; diagnostic imaging ; Models, Biological ; Osteoporosis ; diagnostic imaging

Objective To compare bone mineral density(BMD) at relevant measurement sites between two hips in normal subjects. Methods BMD was measured by dual energy X-ray absorptiometry(DEXA) in the two hips in 70 normal volunteer, 15 to 86 years of age(mean age 53 years). Result Highly significant correlations were found between BMD of the two hips at every measurement sites(r=0.696～0.979, P<0.001),There were small(approximately 2%～3%)but significant differences between BMD of the two hips , The right hip BMD were consistently higher than the left hip BMD at relevant measurement sites (P<0.01)； There were significant positive correlation between BMD and body weight(r=0.289～0.488, P<0.05)except Ward’s triangle. Conclusions BMDs of the two hips are highly correlated at relevant measurement sites; There are strong agreement between BMD of the two hips.

Objective To observe the synergistic action of 17? estradiol(E 2) and L ascorbic acid on the activity of alkaline phosphatase (ALP), cell proliferation and gene expression in osteosarcoma MG 63 cell line, and to study the mechanism of E 2 in treating osteoporosis. Methods MG 63 cells were treated with 10 8 mol/L E 2 with or without 100 ?g/L L ascorbic acid, and then the ALP activity was determined by using ? nitrophenyl phosphate as a substrate. Cell proliferation was measured by ( 3H) thymidine( 3H TdR) incorporation method. mRNA expression of type I collagen, matrix metalloproteinase 1(MMP 1), MMP 2 and osteoprotegerin(OPG) was detected by semiquantitative RT PCR method. Gelatin zymogram was used for the assay of MMP 2 activity. The synergistic action of E 2 and L ascorbic acid on MG 63 cell lines could be evaluated basing on the above indexes since they stand for separately the cell proliferation, gene expression and cell differentiation. Results The action of combined treatment with E 2 and L ascorbic acid on MG 63 cells was obviously stronger than the action using single E 2 or single L ascorbic acid. E 2 and L ascorbic acid increased the ALP activity to 200% ( P

Dual-energy X-ray absorptiometry(DEXA),scanning electron microscopy,and bone biomechanical test were used to assess comprehensively bone quantity and quality of ovariectomized rats. In OVX rats,not only bone mineral density (BMD) of lumbar vertebrae in vivo and vitro,but also BMD of femora (except for R3 region) and proximal metaphysis(R1 region) in vitro decreased obviously (P<0.01)，whose bone loss rates of L5 and L6 were the highest and achieved 13%; the trabeculae of OVX rats were few，fine, and discontinued and there were lacunae on the surface;in OVX rats,both compressive strength of vertebral bodies and the mechanical properties of femora decreased;the falling degree of the former was greater;the maximal compressive power of lumbar vertebrae decreased with 33.32%. We conclude that after 4-month post-ovariectomy, the bone quantity and quality of six-month-old rats decreased, especially in the area of abundant cancellous bone such as vertebral bodies,distal femora; the assessment of the efficiency of new drugs to prevent and treat postmenopausal osteoporosis using rat models should include these drugs' effects to the bone mass, the bone structure, and the bone strength.