80% of low density area in tumor), 10 PR(50%-80%) and 3 NC(0.05). Conclusion For tumor treated with hyperthermia plus radiotherapy, the response evaluation should be based on both the change in the mass size and the percentage of low density area in the tumor.

Objective To evaluate the efficacy and side effects of whole body γ/-knife in patients with limited pancreatic carcinoma. Methods 111 patients with limited pancreatic carcinoma treated with the Stereotactie Gamma Ray Whole-Body Therapeutic System (Whole Body T-knife) were retrospectively an-alyzed. Patients were supine, fixed with a stereotactic body frame and vacuum bag, and then simulated by low-speed computed tomography. GTV, CTV and PTV were defined on the contrast-enhanced CT scans. It was required that 50% isedose line covered 100% of PTV and 70% isedose line covered more than 80% of GTV. The prescription dose was defined as 50% isodose. All patients were treated 5 fractions per week. The fractionated dose was 3-4 Gy for pancreatic head carcinoma, and 4-5 Gy for pancreatic body/tail carcino-ma. Irradiation of 40-51 Gy and 60-70 Gy were delivered to PTV and GTV margins, respectively. Re-suits The complete response rate, partial response rate and overall response rate of the primary tumors were 29.7%, 42.3% and 72.1%, respectively. The follow-up rate was 95.5%. The number of patients fol-lowed-up at 1-,2- and 3-year was 105,89 and 60. The 1-, 2- and 3-year overall survival rates were 49.3%,24.5% and 18.1%. For patients with stage Ⅰ/Ⅱ disease,the number of patients followed-up at 1-,2-,3-,4-and 5-year was 55,44,29,16 and 11 ;The 1-, 2-, 3-,4- and 5-year overall survival rates were 68%,34%, 30%, 21% and 17%, respectively. For patients with stage Ⅲ disease,the number of patients fol-lowed-up at 1-,2- and 3-year was 50,45 and 31 ;The 1-, 2- and 3-year overall survival rates were 28%,14% and 4%, respectively (χ~2=16.67, P=0.000). The acute side effects including nausea, vomiting and diarrhea were 71.2% of RTOG grade 1 -2 and 3.6% of RTOG grade 3. No treatment delay occurred.Conclusions With fractionated dose of 3-5 Gy,5 fractions per week and 40-51 Gy as total dose to PTV,whole body γ-knife is safe and effective to treat limited pancreatic carcinoma. The local control and overall survival could be improved.

Objective To establish chronic stress model of depression in adolescent rats and to examine the effects of different antidepressant treatment on depression and anxiety-related behaviors.Methods Male Wistar rats were given 21-day chronic mild stress (CMS) during their adolescence (postnatal day 30～50, PND30～50).During stress period, rats were treated with fluoxetine (10 mg/kg i.p.) or imipramine (10 mg/kg i.p.), respectively.After stress, rats were tested for behavioral observation using body weight gain, saccharine test, open field and elevated plus-maze (EPM).Results Compared with control/vehicle (n=10) group, stress/vehicle (n=11) group displayed lower weight gain, saccharine preference index and the number of rearing in open field (P<0.05).Antidepressant fluoxetine, but not imipramine reversed anhedonia and the decrease of the number of rearing induced by stress.In addition, compared with early adolescent(PND29) rats, late adolescent (PND52) rats in control/vehicle group exhibited less open arm entries and open arm time, more closed arm time in EPM (P<0.05).Rats in stress/vehicle group showed more open arm entries and less closed arm time than controls(P<0.05).Both fluoxetine and imipramine had no effects on such changes.Conclusions Stress can induce the depression-like behavior in adolescent rats.Fluoxetine, but not imipramine,can effectively reverse anhedonia induced by stress.However, Both antidepressants have no significant effects on stress-induced decrease in developmental increment of anxious behavior during adolescence.These data suggest that chronic mild stress have complicated effects on depressive and anxious behavior in adolescent rats.

Objective To investigate the role of BRAFV600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results. Methods This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAFV600E muta-tion. BRAFV600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction. Results In 93 nodules with benign cytology results but positive BRAFV600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAFV600E mutation analysis will improve sensitivity (Se=94.03％)and negative predictive value (NPV=2.69％) of the thyroid nodules diagnosis than using US-FNA alone(Se=71.03％, NPV=20.76％). Conclusion BRAFV600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAFV600E mutation, thyroidectomy should be considered.

Objective: To investigate the role of BRAF^V600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results. Methods: This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAF^V600E mutation. BRAF^V600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction. Results: In 93 nodules with benign cytology results but positive BRAF^V600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAF^V600E mutation analysis will improve sensitivity (Se=94.03%) and negative predictive value (NPV=2.69%) of the thyroid nodules diagnosis than using US-FNA alone (Se=71.03%, NPV=20.76%) . Conclusion BRAF^V600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAF^V600E mutation, thyroidectomy should be considered.

Objective:To compare the advantages and disadvantages of laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty in the treatment of children with hydronephrosis.Methods:From October 2020 to March 2021, 19 children with hydronephrosis were divided into two groups: intra-renal type and extra-renal type. Among them, 15 were males and 4 were females. The average age of the patients was 3.5 years old (0.2 years old to 16.8 years old), and the average weight was 18.4 kg (5.5 kg to 67.0 kg). The average ERPF of affected kidney before surgery was 35.4%(23.0%-49.8%). All of them were treated with laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty. The operation was performed in accordance with the standard surgical procedures of the guidelines. After the insertion of the trocar, the children in the transmesenteric group were exposed to the renal pelvis by incising the colonic mesangium into the retroperitoneal space, while in the retrocolic group, the peritoneum was cut into the retroperitoneal space to expose the renal pelvis. After that, the steps of incision, cutting, tube placement, and suture of the renal pelvis and ureter were the same in the two groups. Among the 10 cases of the extrarenal type, 6 cases were in the transmesenteric group and 4 cases were in the retrocolic group; among the 9 cases of the intrarenal type, 5 cases were in the transmesenteric group and 4 were in the retrocolic group. There was no statistically significant difference in age, weight, and renal function of the affected side before operation in different surgical approach groups ( P>0.05). The operation time, intraoperative anastomosis time, intraoperative blood loss and postoperative hospital stay were recorded and compared. There was no statistical difference in the age, weight, and renal function of the affected side before the operation. Results:19 cases were followed up for 6 months, no complications such as fever or wound infection occurred. The operation was successfully completed in all patients, no patients were transferred to open surgery, and the hydronephrosis was significantly reduced. Symptoms disappeared in both groups. Of the 19 children. In children with extrarenal type, the operation time of the transmesenteric group and the retrocolic group were (108.8±15.5) min and (132.8±7.6) min, and the intraoperative anastomosis time was (40.7±6.1) min and (51.5±5.5)min, the estimated intraoperative blood loss was (9.5±2.1) ml and (9.3±0.8) ml, respectively, and the postoperative hospital stay was (9.0±1.6) d and (9.3±2.9) d. The operation time and the difference of intraoperative anastomosis time was statistically significant ( P<0.05). In children with intrarenal type, the operation time of the transmesenteric group and the retrocolic group were (136.6±7.9) min and (116.5±13.5) min, and the intraoperative anastomosis time was (52.8±6.9) min and (40.8±6.2), min, the estimated blood loss during the operation was (11.4±2.3) ml and (10.5±0.9) ml, and the postoperative hospital stay was (8.8±1.7) d and (8.0±1.6) d. The operation time and The difference of intraoperative anastomosis time was statistically significant ( P<0.05). The 19 cases were followed up for 6 months, and there was no complications such as fever or wound infection. The volume of hydronephrosis was significantly reduced compared with that before operation, and the renal blood perfusion increased compared with that before operation. The difference was statistically significant ( P<0.05). Conclusion:In terms of shortening the operation time and suture time, for laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty in the treatment of children with hydronephrosis, the transtransmesenteric approach is more advantageous in the treatment of extrarenal hydronephrosis, while the retrocolic approach is more advantageous in the treatment of intrarenal hydronephrosis.

OBJECTIVETo evaluate the association between very low density lipoprotein cholesterol (VLDL-C) and cholesterol absorption and synthesis markers in patients with moderate and high risk of coronary heart disease.

METHODSA total 363 statin-naïve patients with moderate and high risk of coronary heart disease were consecutively recruited from two hospitals in Shanxi and Henan provinces between October 2008 and June 2009. A standard questionnaire and physical examination were performed at baseline. Atorvastatin (20 mg/day) was administered to patients for 4 weeks. Venous blood samples after an overnight fast were collected before and after treatment for measuring VLDL-C and cholesterol absorption and synthesis markers. In qualitative analyses, the baseline level of cholesterol absorption and synthesis markers and their reduction after atorvastatin treatment were categorized into 3 tertile groups.

RESULTS(1) Of 363 patients, 283 patients with mean age of (55.43±9.01)years old with complete data were finally analyzed. The median level of baseline VLDL-C was 1.06 (0.65, 1.86) mmol/L. The median level of baseline cholesterol absorption marker (Campesterol) and cholesterol synthesis marker (Lathosterol) was 6.01 (3.78, 9.45) mg/L and 13.46 (8.30, 21.07) mg/L, respectively. (2) Partial correlation analysis and multiple regression showed the baseline level of VLDL-C was positively correlated with Campesterol (r=0.153, P<0.05) but not with Lathosterol(r=0.182, P=0.173). Furthermore, baseline VLDL-C level significantly increased with tertile of the baseline level of Campesterol in the qualitative analyses(P for trend=0.035). (3) Mean reduction in VLDL-C levels was 38.0% after 4 weeks atorvastatin treatment. VLDL-C reduction was positively correlated with Campesterol reduction (r=0.331, P<0.001). VLDL-C reduction significantly increased with the tertile of Campesterol reduction (P for trend=0.032). But this trend was not observed between VLDL-C level and Lathosterol (P for trend=0.798).

CONCLUSIONThe level of VLDL-C was closely related to cholesterol absorption marker, and further studies are needed to validate if inhibitor of cholesterol absorption (for example by Ezetimibe) could bring about more effective VLDL-C lowering effect in this patient cohort.

Atorvastatin Calcium ; Biomarkers ; Cholesterol ; analogs & derivatives ; Cholesterol, LDL ; Cholesterol, VLDL ; Coronary Artery Disease ; Ezetimibe ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Phytosterols ; Risk Factors

Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in the periodontal region. Although dysbiosis of the local microbial community initiates local inflammation, over-activation of the host immune response directly activates osteoclastic activity and alveolar bone loss. Many studies have reported on the cytokine network involved in periodontitis and its crucial and pleiotropic effect on the recruitment of specific immunocytes, control of pathobionts and induction or suppression of osteoclastic activity. Nonetheless, particularities in the stimulation of pathogens in the oral cavity that lead to the specific and complex periodontal cytokine network are far from clarified. Thus, in this review, we begin with an up-to-date aetiological hypothesis of periodontal disease and summarize the roles of cytokines in the host immune response. In addition, we also summarize the latest cytokine-related therapeutic measures for periodontal disease.
Alveolar Bone Loss ; etiology ; Cytokines ; metabolism ; physiology ; Humans ; Inflammation ; Periodontal Diseases ; Periodontitis ; immunology ; microbiology ; Tumor Necrosis Factor-alpha ; physiology

The biophysical properties of the extracellular matrix (ECM) dictate tissue-specific cell behaviour. In the skeleton system, bone shows the potential to adapt its architecture and contexture to environmental rigidity via the bone remodelling process, which involves chondrocytes, osteoblasts, osteoclasts, osteocytes and even peripheral bone marrow-derived stem/stromal cells (BMSCs). In the current study, we generated stiff (~1 014 ± 56) kPa, Young's modulus) and soft (~46 ± 11) kPa silicon-based elastomer polydimethylsiloxane (PDMS) substrates by mixing curing agent into oligomeric base at 1:5 and 1:45 ratios, respectively, and investigated the influence of substrate stiffness on the cell behaviours by characterizing cell spreading area, cell cytoskeleton and cell adhesion capacity. The results showed that the cell spreading areas of chondrocytes, osteoblasts, osteoclasts, osteocytes and BMSCs were all reduced in the soft substrate relative to those in the stiff substrate. F-actin staining confirmed that the cytoskeleton was also changed in the soft group compared to that in the stiff group. Vinculin in focal adhesion plaques was significantly decreased in response to soft substrate compared to stiff substrate. This study establishes the potential correlation between microenvironmental mechanics and the skeletal system, and the results regarding changes in cell spreading area, cytoskeleton and cell adhesion further indicate the important role of biomechanics in the cell-matrix interaction.
Actins ; Cell Adhesion ; Elastic Modulus ; Focal Adhesions ; physiology ; Humans ; Vinculin ; analysis ; metabolism

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.