ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis， RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase （TRAP） staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay （ELISA） was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression levels of osteocalcin （OCN） and bone sialoprotein （BSP）. Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 （Runx2） and core binding factor β subunit （CBF-β）. Western blot was used to assess the protein expression of Runx2， phosphorylated Runx2 （p-Runx2）， extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， p38 mitogen-activated protein kinase （MAPK）， p-p38 MAPK， and CBF-β. ResultsCompared with the blank group， the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile， the expression levels of p-Runx2， Runx2-CBF-β interaction， BSP and OCN mRNA， p-p38 MAPK， and p-ERK1/2 proteins were significantly decreased （P<0.01）. Compared with the MDA-MB-231 cell supernatant group， Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion （P<0.01）， significantly increased p-Runx2， BSP and OCN mRNA expression， as well as p-p38 MAPK and p-ERK1/2 protein levels， and promoted the interaction between Runx2 and CBF-β （P<0.01）. No significant change in Runx2 expression was observed. Compared to the blank group， the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins （P<0.01）. Compared with the BVD-523 group， both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression （P<0.01）， and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression （P<0.01）， while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation， and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.

Objective To systematically evaluate the risk factors for new-onset atrial fibrillation after off-pump coronary artery bypass grafting (OPCABG). Methods PubMed, EMbase, The Cochrane Library, CNKI, Wanfang, VIP, SinoMed were searched to collect published literature on risk factors for new-onset atrial fibrillation after OPCABG from inception to September 2022. Two authors independently screened, extracted data and evaluated the quality. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies, and Stata 12.0 and RevMan 5.4 softwares were used for meta-analysis. Results A total of 18 researches were included, including 6 354 patients of OPCABG. The NOS scores of the included studies were 6-8 points. Meta-analysis showed that age [MD=2.56, 95%CI (1.61, 3.52), P<0.001], hypertension [OR=1.77, 95%CI (1.18, 2.66), P<0.001], EuroSCORE Ⅱ score [MD=0.70, 95%CI (0.34, 1.06), P<0.001], frequent atrial premature beats or atrial tachycardia [OR=3.77, 95%CI (2.13, 6.68), P<0.001], left atrium diameter (LAD) [MD=1.64, 95%CI (0.26, 3.03), P=0.010], left ventricular ejection fraction (LVEF) [MD=−1.84, 95%CI (−2.85, −0.83), P<0.001], right coronary stenosis [OR=2.49, 95%CI (1.29, 4.81), P=0.006], three-vessel coronary artery lesions [OR=0.73, 95%CI (0.54, 0.97), P=0.030], not using β blockers [OR=0.81, 95%CI (0.69, 0.96), P=0.010], operation time [MD=10.13, 95%CI (8.15, 12.10), P<0.001], duration of mechanical ventilation [OR=2.85, 95%CI (1.79, 3.91), P<0.001] were risk factors for new-onset atrial fibrillation after OPCABG. Conclusion Advanced age, hypertension, high EuroSCOREⅡ score, frequent atrial premature beats or atrial tachycardia, increased LAD, decreased LVEF, right coronary stenosis, three-vessel coronary artery lesions, not using β blockers, prolonged operation time and mechanical ventilation are risk factors for new-onset atrial fibrillation after OPCABG. Due to factors such as the methodology, content and quality of the included literature, the conclusion of this study need to be supported by more high-quality studies.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

ObjectiveT o explore the influence of patch shape for intraventricular tunnel (IVT) construction on biomechanical performance of the double outlet right ventricle after correction. Methods Based on the idealized IVT model, a two-dimensional IVT patch was designed. Six groups of patch models with the rhombic long-to-short axis ratio of 1∶0.625, 1∶0.3, 1∶0.2, 1∶0.15, 1∶0.125, 1∶0.1 were established according to the difference between the long and short axis of the rhombus patch in the turning part, and finite element analysis method was used to numerically simulate the process of stitching, holding and propping up the patch into a three-dimensional (3D) IVT model. Results The maximum stresses on suture line of 6 patch models were mainly concentrated at acute-angle corners of the rhombus. As rhombic long-to-short axis ratio of the patch increased, the maximum stress of the IVT suture line first decreased and then increased, and the volume showed an increasing trend. The pressure difference between two ends of the tunnel first decreased and then increased. The patch with the long-to-short axis ratio of 1∶0.15 had a uniform surface stress distribution, and the maximum stress on the suture line was the smallest. Meanwhile the right ventricular volume was less encroached on, and the pressure difference at both ends of the tunnel was small. Conclusions The IVT shape can influence stresses of suture line, the right ventricle volume and the pressure difference of IVT with non-monotonic variations. The suture effect of the patch with the long-to-short axis ratio of 1∶0.15 is relatively better among the constructed models.

Thyroid cancer is the most common malignant tumor of the endocrine system, and the incidence is increasing year by year, which seriously threatens people's health. Autophagy is a programmed mode of death that can be used as a potential target for anti-tumor therapy and plays an important regulatory role. Leucine-rich repeat kinase 2 (LRRK2) is a protein kinase encoded by PARK8 gene. The recent studies have confirmed that autophagy is closely related to thyroid cancer. This paper analyzes the possible regulatory mechanism of LRRK2 affecting thyroid cancer through autophagy, providing new ideas for basic research and clinical diagnosis and treatment of thyroid cancer.

Objective:To analyze the differences in whole blood selenium (Se), zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), and iron (Fe) levels of rural older adults among areas with different soil selenium levels, and explore the main factors associated with the six nutrient elements status, so as to provide a basis for further evaluating the health risks of people in areas with different soil selenium levels.Methods:Four administrative villages were randomly selected from the Se-deficient (soil Se content < 0.175 mg/kg), Se-sufficient (soil Se content 0.175 - < 0.400 mg/kg), Se-rich (soil Se content 0.400 - < 3.000 mg/kg) and Se-excessive (soil Se content ≥3.000 mg/kg) areas, respectively, in Enshi Tujia and Miao Autonomous Prefecture (Enshi Prefecture) of Hubei Province in 2017 - 2018. And 100 elderly people aged 60 years or older (half male and half female) were randomly selected as the survey subjects in each servey site. The basic information such as general demography and lifestyle was collected through face-to-face questionnaires. Physical examination was performed and fasting venous blood was collected in the morning. The contents of blood Se, Zn, Cu, Mg, Ca, and Fe were determined by inductively coupled plasma mass spectrometry. The main factors associated with the six nutrient elements status were analyzed.Results:A total of 416 subjects were included, including 208 males and 208 females, whose average age was (72.43 ± 5.25) years, and body mass index (BMI) was (22.67 ± 3.49) kg/m 2. There were significant differences of blood Se, Zn, Cu, Mg, Ca and Fe levels between the areas with different Se levels ( Z/F = 288.30, 3.24, 14.81, 29.14, 131.28, 3.37, P < 0.05). Compared with Se-deficient and Se-sufficient areas, blood Se level was higher in Se-rich and Se-excessive areas and blood Zn level was lower in Se-excessive area ( P < 0.05); compared with Se-sufficient area, blood Cu level was lower in Se-deficient, Se-rich and Se-excessive areas, but blood Mg and Ca levels were higher ( P < 0.05), and the blood Fe level was lower in Se-excessive area ( P < 0.05). There were significant differences in the deficiency rates of Se, Zn, Cu, Mg, Ca and Fe among the elderly in different Se level areas (χ 2 = 140.83, 15.39, 31.90, 17.49, 157.60, 30.33, P < 0.01). There were significant differences in blood Zn, Cu, Ca and Fe levels between two gender groups ( P < 0.05); the blood Zn and Fe levels of the smokers were higher than those of the non-smokers, and the blood Cu level was lower than that of the non-smokers ( P < 0.05); the blood Zn and Fe levels of the drinkers were higher than those of the non-drinkers ( P < 0.05). Conclusions:The levels of six nutrient elements in the whole blood of the elderly in areas with different soil Se levels are different. To assess the health risks of the population in areas with different soil Se levels, it is necessary to consider the levels of multiple nutrient elements at the same time.

Objective: To compare the color stability of Biodentine and mineral trioxide aggregate (MTA) within the blood environment in vitro and to further investigate the underlying reasons for such color instability. Methods : We first generated Biodentine and MTA discs with a diameter of 5 mm and a height of 3 mm. 24 discs of each material were randomly divided into two groups: the deionized water group and the defibrinated sheep blood group. Discs of each group were immersed for 1 day or 7 days before assessments. First, all discs were photographed to directly compare the discoloration of Biodentine and MTA. The color degree of the two materials was tested by a spectrophotometer. Then, the high-resolution morphological characteristics were observed by scanning electron microscopy. Finally, the chemical contents of each element in the material were measured by energy-dispersive spectroscopy. Results : Compared to immediately after stripping, a change in the brightness of discs after immersion in defibrinated sheep blood for 1 day was observed only in MTA. On the 7th day after being immersed in blood, the colors of both the Biodentine and MTA discs darkened and turned deep red, but the darkness of the MTA discs increased significantly. The color change of MTA immersed in blood was measured on a spectrophotometer with a greater 7-day ∆E (21.257 ± 0.955) than the Biodentine 7-day ∆E (5.833 ± 0.501) (t=24.781, P < 0.001). MTA exhibits more discoloration as the immersion time goes on. A significant difference was noted between the 1-day ∆E(6.233 ± 0.888) and the 7-day ∆E(t=19.956, P < 0.001) of MTA immersed in blood. However, there was no statistically significant difference between the 1-day ∆E (6.790 ± 0.831) and the 7-day ∆E(t=1.707, P=0.163) of Biodentine immersed in blood. It was observed by scanning electron microscopy that after 7 days of immersion in the defibrinated sheep ablood, the surface porosity of MTA was larger than that of Biodentine, and the crystal edge of MTA became rounded and blunt. The analysis by energy-dispersive X-ray spectroscopy showed that the oxygen content decreased and the bismuth content increased in MTA after immersion in defibrinated sheep blood for 7 days. Zirconium was not detected in Biodentine due to its low radiodensity, but the contents of other elements were stable in Biodentine after immersion in defibrinated sheep blood for 7 days. Conclusion The color stability of Biodentine within the blood environment is better than that of MTA in vitro, which is mainly related to the low surface porosity and stable composition of the anti-radiation agent of Biodentine.

Objective:To investigate the long-term effects of porcine small intestinal submucosa (SIS) biologic mesh in open Lichtenstein tension-free hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 76 patients with unilateral inguinal hernia who underwent open Lichtenstein tension-free hernia repair in 2 medical centers (52 cases in Tianjin People′s Hospital and 24 cases in China-Japan Friendship Hospital) from August 2013 to March 2014 were selected. Based on random number method, patients were allocated into two groups. Patients undergoing Lichtenstein tension-free hernia repair using Biodesign Surgisis mesh were allocated into control group, and patients undergoing Lichtenstein tension-free hernia repair using SIS biologic mesh were allocated into experiment group. Observa-tion indicators: (1) grouping situations of the enrolled patients; (2) postoperative long-term effects. Follow-up was conducted using telephone interview, text message or mail to detect hernia recurrence or death due to other reasons as the end-point event of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented by M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping situations of the enrolled patients: a total of 76 patients were selected for eligibility. There were 38 cases in the control group and the experiment group, respectively. The number of males and females, age, body mass index, cases with intraspinal anesthesia or local anesthesia (anesthesia method), cases with inguinal hernia on the left side or on the right side, cases classified as type Ⅰ, Ⅱ, Ⅲ, Ⅳ or Ⅴ of Gilbert classification, operation time of the control group were 35, 3, (56±15)years, (23.0±2.0)kg/m 2, 22, 16, 16, 22, 9, 16, 0, 11, 2 and (49±15)minutes, respectively. The above indicators of the experiment group were 34, 4, (54±13)years, (22.9±2.2)kg/m 2, 17, 21, 14, 24, 9, 21, 1, 7, 0, and (53±21)minutes, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.157, t=0.532, 0.367, χ2=1.317, 0.220, Z=-0.315, t=-0.765, P>0.05). (2) Post-operative long-term effects: 35 patients of the control group were followed up for (68.8±2.7)months, 4 cases of which died due to other reasons, 1 case had hernia recurrence, 1 case had chronic pain and no foreign body sensation and postoperative infection occurred. Thirty-one patients of the experiment group were followed up for (68.8±2.7)months, with no death or above complications. There was no significant difference in hernia recurrence or chronic pain between the two groups ( P>0.05). Conclusion:The long-term effects of biological mesh in open Lichtenstein tension-free hernia repair is satisfactory and there is no difference in the long-term effects between the domestic SIS biological mesh and Biodesign Surgisis mesh.

Objective To clarify the relationship between intracranial pressure monitoring and prognosis of patients with traumatic brain injury after decompressive craniectomy.Methods From December 2015 to December 2017,48 head-injured patients in Affiliated Suzhou Hospital of Nanjing Medical University were enrolled,who were underwent decompressive craniectomy in this retrospective study.The patients were subdivided into 2 groups based on whether postoperative was monitored (n =19) or not (n =29).The prognosis was evaluated by Glasgow Outcome Scale score,with 1 point of prognosis death,2 to 3 points of poor prognosis,and 4 to 5 points of good prognosis.Count data were expressed as a percentage (％).Count data were expressed as percentage (％).The chi-square test was used to compare the difference in the rate of good prognosis and mortality between the two groups.Results The mortality of monitoring group (10.5％) was significantly lower than that of control group (37.9％) (x2 =4.365 5,P =0.036 7) during hospitalization,The rate of good prognosis in the monitoring group (68.4％) and the control group (44.8％) was not statistically significant (x2 =2.573 8,P =0.108 6).Condusion The study showed that continuous monitoring in patients with severe craniocerebral injury could reduce the mortality of patients during hospitalization,but had no significant effect on the improvement of prognosis.

Objective To explore the sen sation recovery of superficial palmar branc h of the radial artery flap with palmar branch of median nerve and donor si te. Methods From January, 2014 to June, 2016, 12 cases of finger soft tissue defects were repaired with sup erficial palmar branch of the radial artery flap with palmar branch of median nerve. The 2 g tactile sensation, 5 g pain sen sation, 30 g pressure sensation and static two-point discrimination (S2 -PD) of the flap was tested regularly. The S2 -PD of the palmar cutaneous branch of the median nerve were recorded respectively on the affected side and the unaffected side. The results were applied comparative t-test to perform statistical analysis, to observe the sensory recovery of the flap and donor site. Results The flaps survived.Twelve cases was followed-up for 6-18 mont hs. The pressure sensation of about 83.3％ of patients recovered after 2 months and 100％ of patients recovered after 3 months. The tactile sensation of about 91.7％ of patients recovered after 3 months and 100％ of patients recovered after 4 months. The pain sensation of about 91.7％ of patients recovered after 4 months of and 100％ of patients recovered after 5 months. S2-PD of the flap was the average of 8.3 mm in 6 months after operation. There were no significant differences in the S2-PD between the affected group [(12.08±2.15)mm] and unaffected group [(10.58±2.11)mm](P>0.05). And the sensory recovery of the control area of the palmar branch of the median nerve was S4 in 2 cases, S3+ in 9 cases, and S3 in 1 case. The sensory recovery was good. Conclusion Superficial palmar branch of the radial artery flap with palmar branch of median nerve can be used repair the skin defect of the fingers. The flap has a good sensery recovery, and the sensation of the donor area is gradually restored.