Objective To compare the effects of different doses of propofol on cardiac pump function in morbidly obese patients. Methods Forty morbidly obese patients undergoing laparoscopic Roux-en-Y gastric by-pass were randomly divided into lean body weight(LBW)group and total body weight(TBW)group,with 20 cases in each group.In LBW group,patients were induced by propofol with a dose according to LBW(kg)×2.0 mg/kg but in TBW group,patients were induced by propofol depending on TBW of the patients.We monitored the changes of left ventricular ejection fraction(LVEF)and stroke volume(SV)in patients before anesthetic induction(T1)and at 1 min(T2)after propofol administration.At the same time,we monitored invasive arterial pressure,noninvasive arterial pressure,BIS,and SpO2.Results Compared with those measured at T1,LVEF and SV were decreased af-ter the induction of anesthesia in the 2 groups(P < 0.05);compared with LBW,TBW had greater influence on LVEF and SV after the induction of anesthesia(P<0.05);compared with those at T1,non invasive arterial blood pressure,invasive arterial blood pressure and mean arterial pressure decreased after theinduction of anesthesia (P<0.05);compared with LBW,TBW had no significant effect on noninvasive arterial blood pressure,invasive arterial blood pressure and mean arterial pressure after the induction of anesthesia(P < 0.05);BIS was less than 50 after the induction of anesthesia in 2 groups. Conclusion Propofol induction with a LBW-dependent dose has less influence on cardiac pump function in morbidly obese patients while ensuring the depth of anesthesia.

As the world’s population ages, age-related cognitive decline and dementia are becoming important challenges for geriatric care. Despite the ongoing search for solutions to address cognitive decline, effective interventions have not yet been established. There is increasing evidence from clinical, epidemiological, and animal studies that masticatory dysfunction due to occlusal disharmony is a risk factor for cognitive decline and an increased incidence of dementia. The mechanisms may involve altered nutritional intake, decreased cerebral blood flow, chronic stress, and hippocampal morphological function. These findings suggest that maintaining and adequately restoring the entire masticatory system has a positive impact for the prevention of cognitive decline.

ObjectiveTo explore the effect of sweroside on the protection of cardiac systolic/diastolic function during ischemia/reperfusion （I/R） injury. MethodTwenty-four healthy male SD rats were randomly divided into control group， model group， 10 μmol·L^-1 sweroside group and 1 μmol·L^-1 digoxin group. The I/R injury was modeled by Langendorff and ligation of the left anterior descending coronary artery. The infarct size in each group was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining and hemodynamic parameters such as left ventricular diastolic pressure （LVDP）， left ventricular end-diastolic pressure （LVEDP）， left ventricular end-systolic pressure （LVESP）， maximum rate of rising of left ventricular pressure （+dp/dt_max） and maximum rate of decreasing of left ventricular pressure （-dp/dt_max） of rat isolated heart were detected by Powerlab. In addition， neonatal rat cardiomyocytes （NRCMs） were isolated and randomly divided into control group， model group， 1 μmol·L^-1 sweroside group and 10 μmol·L^-1 sweroside group. Hypoxia/reoxygenation （H/R） injury model was established. Cardiac systolic function and calcium transients were examined by multi-functional cell imaging analyzer and laser confocal microscope. Furthermore， real-time polymerase chain reaction（Real-time PCR） was used to verify the mRNA expression of excitation-contraction coupling genes such as L-type calcium channel （Cacnb2）， cytochrome c oxidase subunit 6A2 （Cox6a2）， troponin （Tnnc1， Tnni3， Tnnt2）， actin （Actc1）， and myosin （Myh6， Myl2， Myl4） according to the results of previous transcriptome sequencing and literature investigation. Differentially expressed genes were subjected to cluster analysis. ResultCompared with the conditions in the control group， increased cardiac infarction size （P<0.01） and LVEDP （P<0.01） and decreased LVDP （P<0.01） and LVESP （P<0.05） were observed in the model group， with +dp/dt_max of increasing trend while -dp/dt_max decreasing. Moreover， the cell viability， heart rate and contraction amplitude of NRCMs was reduced （P<0.01）， while the contraction duration， time to peak and relaxation time was elevated （P<0.01） in the model group. Interestingly， sweroside could reverse these indicators （P<0.05）. In addition， the expression of Cacnb2， Cox6a2， Tnnc1， Tnni3， Tnnt2， Actc1， and Myh6， Myl2， and Myl4 was down-regulated in the model group （P<0.05， P<0.01）， but sweroside could up-regulate the expression of the above genes （P<0.05）. ConclusionSweroside effectively regulated Ca²⁺ level in NRCMs， enhanced cardiac systolic function， and protected against H/R injury by regulating excitation-contraction coupling.

ObjectiveTo establish and evaluate a mouse model of heart failure with Qi deficiency syndrome. MethodForty-four KM mice were randomly divided into sham operation group， model group， and modified Si Junzitang group （12.89 g·kg^-1）. The model group and the modified Si Junzitang group underwent thoracic aortic constriction （TAC）， while the sham operation group only underwent suture without constriction. Echocardiography and pathological examination were used to assess the heart failure model and evaluate the pharmacological effects. Macroscopic characterization， microscopic biology， and formula identification were conducted to collect general signs， body weight， open-field behavior， grip strength， mitochondrial ultrastructure， and other macroscopic and microscopic characteristics of mice. Mitochondrial fission and fusion protein expression were measured to determine the syndrome type. ResultEight weeks after TAC， compared with the sham operation group， the model group showed a significant decrease in left ventricular ejection fraction （LVEF） （P<0.01）， and modified Si Junzitang improved LVEF in mice （P<0.05）. Hematoxylin-eosin （HE） staining of the heart showed inflammatory cell infiltration and thickening of blood vessel walls in the model group， which was significantly improved by modified Si Junzitang. After 6-8 weeks， compared with the sham operation group and the modified Si Junzitang group， the model group exhibited significant hair loss， hair yellowing， decreased activity， and depression. Moreover， compared with the sham operation group， the model group had a significantly lower increase in body weight （P<0.05）， while the modified Si Junzitang group showed a significant increase in body weight （P<0.05） compared with the model group. After 6-8 weeks， compared with the sham operation group， the model group showed a significant decrease in open-field distance and speed （P<0.05）， while the modified Si Junzitang group exhibited significantly improved open-field distance and speed in the 8^th week （P<0.05）. After 6-8 weeks， compared with the sham operation group， the model group exhibited a significant decrease in maximum grip strength （P<0.05）， while the modified Si Junzitang group showed a significant increase in maximum grip strength 8 weeks after TAC （P<0.05）. Transmission electron microscopy of the gastrocnemius muscle showed uneven muscle tissue matrix， mitochondrial swelling， increased volume， matrix dissolution， ridge loss， and vacuolization in the model group， while modified Si Junzitang improved mitochondrial swelling， ridge fracture， and matrix vacuolization. Western blot analysis showed that the expression of the kinetic associated protein 1 （DRP1） in the gastrocnemius muscle of the model group significantly increased （P<0.01）， and the expression of mitochondrial fusion hormone 1 （MFN1） significantly decreased （P<0.05） as compared with those in the sham operation group. Furthermore， compared with the model group， the modified Si Junzitang group exhibited a significant decrease in the expression of DRP1 （P<0.05） and a significant increase in MFN1 expression （P<0.01）. ConclusionMice exhibited significant manifestations of qi deficiency syndrome 6-8 weeks after TAC， accompanied by abnormal mitochondrial morphology and function in the gastrocnemius muscle， which were significantly improved by modified Si Junzitang.

Occlusal disorder is an abnormal condition in which the static and dynamic relations between the upper and lower teeth are not well aligned . The most common occlusal disorder in clinical practice is the inability to reach the intercuspal position due to early contact of individual points or occlusal interference due to occlusal high points, which can lead to periodontal tissue damage, decreased masticatory function, temporomandibular joint and muscle discomfort; these results can occur through the overactivation of the locus coeruleus-sympathetic-adrenal medullary system and hypothalamic-pituitary-adrenal axis induce elevated serum corticosteroid levels, which leads to chronic stress in the body. This article reviews the effects of chronic stress caused by occlusal disorder on bone tissue, stomatognathic system, emotional health and cognitive function. It has been found that occlusal disorders not only result in the loss of bone in the oral cavity, the reduction of bone mass in the whole body and damage to the local function of the stomatognathic system but also negatively affect the body’s anxiety, sleep, cognitive function and spatial memory ability as a result of the neuroendocrine changes . In recent years, concern about occlusal disorders has been on the rise. Early detection and timely adjustment of uncoordinated occlusion has become an issue that cannot be ignored in the clinic.

Implant dentures have become the main method for the treatment of dentition defects or complete edentulism. However, due to the lack of periodontal ligament and periodontal ligament proprioceptors, implant dentures have very limited cushioning and sensing capabilities and are prone to occlusal overload. As a risk factor for peri-implantitis, occlusal overload seriously threatens the stability and success rate of implant dentures. This paper reviews the occlusal overload of implant dentures, the causal relationship between occlusal overload and plaque biofilms in peri-implantitis, the mechanism by which occlusal overload promotes peri-implantitis, and the effect of reasonable clinical occlusal adjustment on healing. This review shows that occlusal overload is closely related to the occurrence of peri-implantitis. Occlusal overload can promote the process of peri-implantitis by increasing the release of inflammatory factors and mechanical transduction mechanisms. The intervention of the patients’ bad bite habits and occlusal adjustment can promote the healing of peri-implantitis. At present, there is no uniform standard ideal experimental model for occlusal overload. The phenomenon and mechanism of bone resorption around the implant caused by overload force still need further observation and research, which will help determine the intensity, direction and timing of occlusal loading to guide clinical occlusal adjustment.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.