Objective: To investigate the association between frailty and type 2 diabetes mellitus (T2DM) using a bidirectional two-sample Mendelian randomization (MR) analysis, so as to provide the evidence for the prevention and control of frailty and T2DM. Methods: Frailty status was assessed using the Fried Frailty Score (FFS), with aggregated data sourced from 386 565 European samples in the UK Biobank. The T2DM data were obtained from the summary results of genome-wide analysis published by the Diabetes Genetics Replication and Meta-analysis Consortium, excluding the UK Biobank data, including 455 313 European samples. Eligible single nucleotide polymorphism site were selected from the FFS and T2DM summary data as instrumental variables. The bidirectional MR analysis was performed using the inverse-variance weighted method. The heterogeneity was assessed using the modified Cochran Q test. The horizontal pleiotropy of instrumental variables was examined using MR-Egger regression. The robustness of the results was evaluated using the leave-one-out method. The bias was tested using funnel plot. Results: The forward MR analysis revealed a statistically significant association between increased FFS and an increased risk of T2DM (OR=2.280, 95%CI: 1.169-4.447). The reverse MR analysis showed a statistically significant association between T2DM and increased FFS (β=0.026, 95%CI: 0.012-0.041). Both bidirectional MR results were robust, with no horizontal pleiotropy of the instrumental variables was found (all P>0.5); and the funnel plots did not show significant basis. Conclusion The study found a bidirectional causal association between frailty and T2DM.

Objective To evaluate the effect of sevoflurane postconditioning on autophagy during focal cerebral ischemia-reperfusion (I/R) in rats.Methods Forty-five clean-grade healthy male SpragueDawley rats,weighing 280-350 g,were divided into 3 groups (n=15 each) using a random number table method:sham operation group (S group),cerebral I/R group (I/R group) and sevoflurane postconditioning group (SP group).Focal cerebral I/R injury model was established by Zea-Longa method in chloral hydrate-anesthetized rats.The animals in SP group inhaled 2.4％ sevoflurane for 30 min starting from onset of reperfusion.The expression of autophagy-related proteins LC3 and beclin-1 was detected by Western blot at 2 h of reperfusion.The cerebral cortex was removed for examination of the morphology and number of autophagosomes with an electron microscope.Neurological deficit was assessed and scored at 24 h of reperfusion.Rats were sacrificed at 72 h of reperfusion for determination of the cerebral infarct size.Results Compared with S group,the neurological deficit score was significantly increased,the percentage of cerebral infarct size was increased,LC3Ⅱ/LC3Ⅰ ratio in cerebral cortex was increased,the expression of beclin-1 was up-regulated,and the number of autophagosomes was increased in I/R and SP groups (P＜0.05).Compared with I/R group,the neurological deficit score was significantly decreased,the percentage of cerebral infarct size was decreased,LC3Ⅱ/LC3Ⅰ ratio in cerebral cortex was decreased,the expression of beclin-1 was down-regulated,and the number of autophagosomes was reduced in SP group (P＜0.05).Conclusion Sevoflurane postconditioning mitigates focal cerebral I/R injury through inhibiting autophagy in rats.

OBJECTIVE: To investigate the involvement of ephrinB2 in periodontal tissue remodeling in compression areas during orthodontic tooth movement and the effects of compressive force on EphB4 and ephrinB2 expression in osteoblasts and osteoclasts. METHODS: A rat model of experimental tooth movement was established to examine the histological changes and the localization of ephrinB2 in compressed periodontal tissues during experimental tooth movement. RAW264.7 cells and ST2 cells, used as precursor cells of osteoclasts and osteoblasts, respectively, were subjected to compressive force in vitro. The gene expression of EphB4 and ephrinB2, as well as bone-associated factors including Runx2, Sp7, NFATc1, and calcitonin receptor, were examined by quantitative real-time polymerase chain reaction (PCR). RESULTS: Histological examination of the compression areas of alveolar bone from experimental rats showed that osteoclastogenic activities were promoted while osteogenic activities were inhibited. Immunohistochemistry revealed that ephrinB2 was strongly expressed in osteoclasts in these areas. Quantitative real-time PCR showed that mRNA levels of NFATc1, calcitonin receptor, and ephrinB2 were increased significantly in compressed RAW264.7 cells, and the expression of ephrinB2, EphB4, Sp7, and Runx2 was decreased significantly in compressed ST2 cells. CONCLUSIONS: Our results indicate that compressive force can regulate EphB4 and ephrinB2 expression in osteoblasts and osteoclasts, which might contribute to alveolar bone resorption in compression areas during orthodontic tooth movement.
Animals ; Bone Resorption* ; Gene Expression ; Immunohistochemistry ; Models, Animal ; Osteoblasts* ; Osteoclasts* ; Rats ; Real-Time Polymerase Chain Reaction ; Receptors, Calcitonin ; RNA, Messenger ; Tooth Movement*

This study was designed to investigate the effects of wheat grain moxibustion on the immune function of mice immunosuppressed by cyclophosphamide,and to delve into the potential mechanisms by analyzing factors related to NF-κB signaling pathway.Sixty SPF-grade ICR mice were randomly allocated into four groups:blank group,model group,traditional Chinese medicine group and wheat grain moxibustion group,with 15 mice in each group.Immunosuppression was induced in mice of the model,traditional Chinese medicine and wheat grain moxibustion groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg daily for three days,while mice of the blank group received an equivalent volume of saline.The traditional Chinese medicine group was treated with oral administration of Zhēn Qí Fú Zhèng granules,and the wheat grain moxibustion group was treated with wheat grain moxibustion at"Da Zhui,"bilateral"Zu San Li,"and bilateral"San Yin Jiao"once a day for seven consecutive days.After corresponding treatment,spleens were harvested from the mice of different groups for pathological examination,and enzyme-linked immunosorbent assay(ELISA)was utilized to measure the serum levels of IL-2,IL-4,TNF-α and IFN-γ.Additionally,Western blot analysis was conducted to assess the protein expression levels of IκBα and P-IκBα in spleen tissue.Compared with the blank group,mice in the model group exhibited poorer general conditions,significantly reduced white blood cell(WBC)count(P＜0.01),extensive damage in spleen tissue,significant decreases in serum IL-4 and IL-2 concentrations,increases in TNF-α and IFN-γ levels(P＜0.01),lower level of P-IκBα protein in spleen tissue(P＜0.01),and higher level of IκBα protein(P＜0.01).These changes mentioned above were reversed in mice of both the wheat grain moxibustion group and the traditional Chinese medicine group(P＜0.01).Compared to the traditional Chinese medicine group,on the last day of treatment,the wheat grain moxibustion group showed slightly higher WBC counts(P＜0.05),better tissue repair,and lower levels of IFN-γ(P＜0.01).In conclusion,wheat grain moxibustion can affect the activity of NF-κB signaling pathway by regulating the relative expression of IκBα and P-IκBα,and then regulate the immune response of the body,thus play a role in alleviating the immunosuppression caused by cyclophosphamide.

Objective To reduce the risk of radiation-induced cardiac injury in patients with left breast cancer after breast-conserving surgery by multileaf collimator (MLC) shielding technique.Methods A total of 18 patients with left breast cancer after breast conserving surgery were selected to obtain 3DCT and 4DCT images at free breathing state.The target area was identified on the 3DCT image by registration with 4DCT images and to develop a hybrid intensity-modulated treatment plan (H_IMRT) and a heart sparing hybrid intensity-modulated treatment plan (HSH_IMRT) to introduce MLC shielding technology to reduce the cardiac exposure dose,and to perform dosimetry verification of the treatment plan by using the Compass verification system.The prescription dose was 50 Gy in 25 fractions.The dosimetry parameters of the target area and the organs at risk were compared between the two treatment plans and the dose verification result.Results The result of the treatment plan showed that compared with H_IMRT,the dose uniformity of the target area of HSH_IMRT was better,and the difference of conformability was not statistically significant (P＞0.05).The mean dose of the whole heart decreased by 23.67％ (t =13.693,P＜0.05) compared with the former.Dmax and D of other substructures of the heart were lower than the former.The result of dose verification showed that there was no statistically significant difference in uniformity and conformity between the two planned target doses (P＞ 0.05).The mean dose of the whole heart of HSH_IMRT was 24.88％ (t =13.782,P＜0.05) lower than that of H_IMRT,and except for the left ventricle and right ventricle,the Dmax of other heart substructures and D of all heart substructures decreased.Both the planned and the dose verification result showed that the V20 and the D of the affected lung were lower in HSH_IMRT.Conclusions Reasonable introduction of MLC shielding technology in H_IMRT can reduce the exposure dose of cardiac and further reduce the risk of radiation damage in heart.

Objective To assess the protective effect of low melting point lead and field margin on the opposite testicular in testicular seminoma patients during postoperative radiation.Methods A patient with stage Ⅰ seminoma was selected and his phantom measurement was carried out.The PTW 0.6 cm3 type ionization chamber was used to measure the absorbed dose under the conditions of no lead and low melting point lead with thickness of 3,5,7,10 and 15 mm at different distances from the field edge,respectively.Results Under different lead thickness conditions,the measurement result and the distance between the measured points and the boundary of the field were exponentially attenuated.The relative target dose dropped from 8.41％ at 1 cm to 0.61％ at 25 cm without lead blocking,and dropped from 4.55％,3.98％ and 3.47％ at 1 cm to0.27％,0.21％ and0.17％ at 25 cm with 3,5,7 cmlead,respectively.With 10 mm lead,it dropped from 2.55％ at 1.5 cm to0.15％ at25 cm,and 1.86％ at2 cm to0.13％ at 25 cm with 15 mm lead.The lead shield of 3,7 and 15 mm thickness can be used to reduce the scatter dose of testis to below 0.5 Gy during radiotherapy for seminoma.Conclusions An appropriate thickness of low melting point lead might reduce the dose of testis conveniently and effectively,which would be beneficial to protect the fertility of the patients with testicular seminoma.

Objective:To investigate the impact of early blood glucose fluctuations after acute multiple injuries on post-traumatic stress disorder (PTSD).Methods:This study was a case-control study. From March 2022 to March 2023, patients with acute multiple injuries who were admitted to the ICU of the Affiliated Hospital of Xuzhou Medical University were selected. According to whether complicated with traumatic brain injury (TBI), the patients were divided into TBI group and non-TBI group. Early post-traumatic blood glucose fluctuations were observed, including stress-induced hyperglycemia (SIH), initial blood glucose value on admission, blood glucose extreme, short-term glycemic variability (GV) and other related indicators. The 72-hour glucose coefficient of variation (Glu-CV) was used to reflect short-term GV. After 1 month, the PTSD checklist for DSM-5 (PCL-5) was used to assess the patient's symptoms of PTSD. The patients were divided into PTSD group and non-PTSD group according to PCL-5 score ≥38. The differences in short-term glucose fluctuations in each groups were compared; the risk factors of PTSD were analyzed by logistic regression; the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of related indicators on the incidence of PTSD.Results:159 patients with acute multiple injuries were selected and defined as the TBI group ( n=94) and non-TBI group ( n=65). The incidence of PTSD, PCL-5 scale scores, the incidence of SIH and 72 h Glu-CV in the TBI group were significantly higher than the non-TBI group (all P<0.05). The incidence of SIH and 72 h Glu-CV in the PTSD group were significantly higher than the non-PTSD group (both P<0.05). Multivariate logistic regression analysis showed that 72 h Glu-CV ( OR=1.333, 95% CI: 1.028-1.727, P=0.030) was the independent risk factor for PTSD after acute multiple injuries, and the area under the ROC curve was 0.861 (95% CI: 0.789-0.933, P<0.001), the sensitivity was 62.9% and the specificity was 93.5%. Conclusion:Patients with acute multiple injuries with TBI are more likely to have early glucose fluctuations and develop PTSD, and increased short-term glucose variability is the independent risk factor for PTSD after acute multiple injuries.

Fecal microbiota transplantation(FMT)of human fecal samples into germ-free(GF)mice is useful for establishing causal relationships between the gut microbiota and human phenotypes.However,due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms,it may not be possible to replicate human phenotypes in mice through FMT;similarly,treatments that are effective in mouse models may not be effective in humans.In this study,we aimed to identify human gut microbes that undergo significant and consistent changes(i.e.,in relative abundances)after transplantation into GF mice in multiple experimental settings.We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota pro-files from 1713 human-mouse pairs.Strikingly,on average,we found that only 47％of the human gut microbes could be re-established in mice at the species level,among which more than 1/3 under-went significant changes(referred to as"variable taxa").Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimen-tal settings.Consequently,about 1/3 of human samples changed their enterotypes,i.e.,significant changes in their leading species after FMT.Mice fed with a controlled diet showed a lower enter-otype change rate(23.5％)than those fed with a noncontrolled diet(49.0％),suggesting a possible solution for rescue.Most of the variable taxa have been reported to be implicated in human dis-eases,with some recognized as the causative species.Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes,provide useful informa-tion for researchers using mice in gut microbiota studies,and call for additional validations after FMT.An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.

Background: Expression of microRNA⁃320 (miR⁃320) is down regulated in acute pancreatitis, and the mechanism of its effect on acute pancreatitis is still unclear. Aims: To investigate the effect of miR⁃320 on intestinal injury in rats with acute pancreatitis and its mechanism. Methods: Rats were randomly divided into sham operation group, model group, miR⁃ 320 agonist group (agomir miR ⁃ 320 group), miR ⁃ 320 agonist control group (agomir NC group), JAK2 inhibitor group (AG490 group), and NF⁃κB pathway inhibitor group (PDTC group). The rat model of acute pancreatitis was established by retrograde injection of 5% sodium taurocholate to the bile duct. The automatic biochemical analyzer was used to detect serum levels of amylase and lipase; ELISA assay was used to detect serum levels of TNF⁃α and IL⁃1β; HE staining was used to observe the pathological changes of rat pancreas and ileum; TUNEL staining was used to observe cell apoptosis in rat ileum; real⁃time fluorescent quantitative PCR (RT⁃qPCR) was used to detect the expression of miR⁃320 in ileum tissue; Western blotting method was used to detect the expressions of JAK2/STAT3 and NF⁃κB signaling pathway related proteins in ileum. Results: Compared with sham operation group, the pancreas and ileum were severely injured in model group, and the pathological score and ileum cell apoptosis were significantly increased (P<0.05), serum levels of amylase, lipase, TNF⁃ α, and IL⁃1β were significantly increased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly decreased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly increased (P<0.05). Compared with model group, the pathological damages of pancreas and ileum in agomir miR ⁃ 320 group, AG490 group and PDTC group were reduced, and the pathological score and ileum cell apoptosis were significantly decreased (P<0.05), serum levels of amylase, lipase, TNF ⁃ α, and IL ⁃ 1β were significantly decreased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly increased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃ p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly decreased (P<0.05). Conclusions: MiR⁃320 can improve the intestinal injury in rats with acute pancreatitis by inhibiting the activation of JAK2/STAT3 and NF⁃κB signaling pathways.

Objective:To evaluate the dose calculation accuracy of cone-beam CT (CBCT) image by actual measurement method.Methods:CBCT images of 60 patients in the Second Affiliated Hospital of Soochow University from September, 2021 to May, 2022 were retrospectively analyzed. CBCT images of full-fan and half-fan scanning of the head, half-fan scanning of the chest and pelvis were obtained by the Varian OBI system. Hounsfield unit - electron density (HU-ED) curves corresponding to the scanning conditions were established with CIRS electron density phantom. The radiotherapy plans were designed on the CBCT images, and the dose calculation results of the detection point were compared with the ionization chamber measurement results to analyze the dose error. Then, three-dimensional dose verification system was adopted to detect the accuracy of the CBCT image radiotherapy plans implementation process in 60 patients, and the accuracy of dose calculation was verified according to the D 99%, D mean, D 1% of target volume, D mean and D 1% of organs at risk (OAR), and the γ pass rate. Results:In point dose detection in phantom, the dose calculation errors of CBCT images in the above four scanning patterns were -1.06%±0.87%、-1.67%±0.86%, 0.91%±0.73%, -1.54%±0.90%, respectively. In dosimetric verification based on patients' CBCT image treatment plan, the mean difference of D mean, D 99%, and D 1% of planning target volume (PTV) in all scanning modes were not higher than 2%, and the D mean and D 1% differences of other OAR were not higher than 3%, except for the lens of patients in the head. The average γ values of target volume and OAR were less than 0.5 under the criteria of 3%/2 mm. Conclusions:Under the condition of correctly establishing HU-ED curves, intensity-modulated radiation therapy (IMRT) / volumetric-modulated arc therapy (VMAT) planning based on CBCT images can be employed to estimate and monitor the actual dose to target volume and OAR in adaptive radiotherapy. Full-fan scanning patterns can further improve the accuracy of dose calculation for the head of patients.