Objective To observe the effects of different administration doses of dexmedetomidine on the circulatory system and stress response in patients undergoing extracorporeal coronary artery bypass grafting(OPCABG).Methods Ninety-six patients who underwent OPCABG in our hospital from October 2021 to October 2023 were selected and divided into two groups using simple randomization method.Group A was administered dexmedetomi-dine at a dose of 0.5 μg/kg over 10 minutes before anesthesia induction,followed by a maintenance dose of 0.5 μg/(kg·h)infused until the end of the surgery,while group B was administered dexmedetomidine at a dose of 0.8 μg/kg for 10 min before anesthesia induction,followed by a maintenance dose of 0.8 μg/(kg·h)until the end of the operation.The two groups were compared in terms of cardiac index(CI),heart rate,mean arterial pressure(MAP),intrathoracic blood volume index(ITBI),bispectral index(BIS),and systemic peripheral vascular resistance index(SVRI)before anesthesia started(T0),at the immediate moment of intubation(T1),at the immediate moment of the start of the surgery(T2),at the time of sawing of the sternum(T3),and at the immediate moment of extubation(T4).Additionally,the two groups were compared in terms of cortisol(Cor),Angiotensin Ⅱ(Ang Ⅱ)levels,safety and postoperative awakening time.Results The two groups showed no differences in operation time,anaesthesia time,bleeding and urine volume(P＞0.05),but group B demonstrated less intraoperative use of cisatracurium compared to group A(P＜0.05).At T0,the two groups showed no difference in heart rate and MAP(P＞0.05),but higher heart rate and MAP at T1 and T3 than at T0.Group A was observed to have higher heart rate and MAP at T4 than at T0,while group B showed no significant differences in heart rate and MAP at T4 com-pared to them at T0(P＞0.05).At T2 and T4,Group B showed significantly lower heart rate and MAP compared to group A(P＜0.05).At T0,the two group had no differences in terms of CI,CO,ITBI,and SVRI(P＞0.05).Both groups showed significantly lowered levels of CI,CO,ITBI,and SVRI at T1-T4 than at T0(P＜0.05),but demonstrated no differences in the levels of CI,CO,ITBI,SVRI at T0-T4(P＞0.05).At T0,both groups had no difference in BIS values(P＞0.05),but showed significantly decreased BIS values at T1-T4 compared with those at T0(P＜0.05).At T2-T4,group A showed significantly lower BIS values compared with group A(P＜0.05).The two groups had no difference in postoperative awakening time compared with group A(8.12±1.88 min vs.8.05±1.97 min,P＞0.05).Preoperatively,the two groups had no differences in Cor and Ang Ⅱ(P＞0.05).However,at 6 h postoperatively,both groups showed significantly elevated Cor and AngⅡ values compared to preoperatively(P＜0.05),and group B showed signifantly lower values of Cor and AngⅡ compared to group A(P＜0.05).The two groups had no difference in the adverse reactions(6.25%vs.8.33%,P＞0.05).Conclusion Dexmedetomidine administered at the dose of 0.8 μg/(k·h)rather than at the dose of 0.5 μg/(k·h)for managing OPCABG results in more stable hemodynamics during surgery,yielding better sedative effect,milder postoperative stress response,and no increase in adverse reactions.

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum （ER） stress and reducing urinary protein in the rat model of diabetic nephropathy （DN）. MethodSeventy-five SD rats were randomized into normal， model， low-， medium-， and high-dose （4.37， 8.73， 17.46 g·kg^-1， respectively） modified Shengjiangsan， and irbesartan （0.014 g·kg^-1） groups， with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage， once a day， for 8 consecutive weeks. After the last administration， the levels of glucose （GLU） in the blood， 24-hour urinary protein （24 h-UTP）， and superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in the renal tissue were measured. Hematoxylin-eosin staining， periodic acid-Schiff staining， and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin， podocin， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， and activating transcription factor 4 （ATF4） in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 （Sirt1）， phosphorylated （p）-protein kinase RNA-like endoplasmic reticulum kinase （PERK）， and p-eukaryotic translation initiation factor 2 alpha （eIF2α） in rat kidneys. ResultCompared with the normal group， the modeling caused pathological damage to the kidneys， elevated the levels of GLU and 24 h-UTP （P<0.05）， up-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and down-regulated the protein level of Sirt1 （P<0.05） in rat kidneys. Compared with the model group， modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels （P<0.05）， alleviated the pathological damage in the renal tissue， down-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and up-regulated the protein level of Sirt1 （P<0.05）. ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue， thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.

Purpose To evaluate the consistency and repeatability of cerebral blood flow(CBF)values measured by automatic segmentation of region of interest(ROI)and arterial spin labeling(ASL)functional image fusion in hippocampal sclerosis patients with medial temporal lobe epilepsy.Materials and Methods From January 2021 to October 2022,a total of 52 patients with medial temporal lobe epilepsy confirmed by MRI or pathology in General Hospital of Ningxia Medical University were retrospectively collected.All subjects were scanned on 3.0T MRI to obtain axial T1 weighted three-dimensional magnetization reserve gradient echo(3D-T1W1-MPGAGE)sequence and three-dimensional pseudo continuous ASL sequence.The 3D-T1W1-MPGAGE imaging were automatically segmented.Two physicians used the freeview visualization interface of freeSurfer software to fuse the ROI and ASL functional images of the hippocampal subregions and to measure the CBF values.The intra-observer and inter-observer consistency and repeatability were evaluated and analyzed.The consistency analysis and repeatability evaluation were performed via intraclass correlation coefficient(ICC),Bland-Altman diagram and Wilcoxon rank sum test.Results The ICC of CBF values measured by two physicians were all>0.750,with an average of 0.868±0.095.The ICC of left and right hippocampal subregions were as follows:subiculum(SUB):0.818/0.801,cornu ammonis(CA)1:0.920/0.907,CA2-3:0.759/0.978,CA4:0.757/0.758 and dentate gyrus(DG):0.990/0.991;The ICC delineated by the same physician's ROI were all>0.990 with an average of 0.994±0.002.The ICC of left and right hippocampal subregions were as follows:SUB:0.993/0.993,CA1:0.996/0.995,CA2-3:0.989/0.994,CA4:0.992/0.995 and DG:0.993/0.996.The Bland-Altman diagram showed the scatter distribution and consistency,and the coefficient of repeatability was obtained.The same observer had certain repeatability for the fusion measurement of automatic segmentation ROI and ASL functional images.Conclusion The CBF values measured by fusing ROI and ASL functional images of automatically segmented hippocampal subregion have higher consistency and repeatability.

Hepato-pancreato-biliary diseases (HPBD) are often complicated. The diagnosis and treatment of HPBD involve many disciplines. The malignant degree of hepatobiliary pancreatic system is high, and the prognosis of patients is poor. The multidisciplinary team (MDT) brings specialists from different disciplines together to make a comprehensive and individualized treatment for patients. MDT is emerging in HPBD in recent years. MDT helps improve the accuracy of diagnosis and prognosis. However, there are still some controversies and obstacles in the application of MDT for patients with HPBD. We reviewed the development, current status and experience of MDT in the field of HPBD, analyze the current controversy and obstacles, and providing reference for its future application.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective:To investigate the relationship between thyroid function abnormality-immune related adverse event (TFA-irAE) and treatment efficacy and survival in advanced cancer patients treated with programmed death-1 (PD-1) inhibitors.Methods:The clinical data of 90 patients with advanced cancer who received 6 cycles of PD-1 inhibitor treatment from January 2021 to June 2022 in Department of Oncology of Yuncheng Central Hospital Affiliated to Shanxi Medical University were collected. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured by chemiluminescence immunoassay in patients after PD-1 inhibitor treatment, and the incidence of TFA-irAE was observed in the patients after 6 cycles of therapy. According to the occurrence of TFA-irAE, the patients were divided into TFA-irAE occurrence group ( n=40) and TFA-irAE non-occurrence group ( n=50), the therapeutic efficacy and survival of the two groups were calculated and compared. The thyroid function indexes of patients with different efficacy (33 cases in effective group and 57 cases in ineffective group) and patients with different prognosis (30 cases in survival group, 60 cases in death group) were compared, and the influencing factors of efficacy and survival were analyzed by multivariate logistic regression and Cox analysis. Kaplan-Meier survival curve was drawn, and the survival of TFA-irAE occurrence group and TFA-irAE non-occurrence group were compared by log-rank test. Results:One year after treatment, the treatment effective rate of TFA-irAE occurrence group and TFA-irAE non-occurrence group were 42.5% (17/40), 32.0% (16/50), respectively, with no statistically significant difference ( χ2=1.06, P=0.304). After 6 cycles of PD-1 inhibitor treatment, serum levels of TSH [ (2.56±0.41) mU/ml vs. (3.11±0.53) mU/ml], TPOAb [ (56.78±5.72) U/ml vs. (62.67±6.31) U/ml] and TGAb [ (81.57±8.23) U/ml vs. (92.34±9.31) U/ml] in the effective group were significantly lower than those in the ineffective group, with statistically significant differences ( t=4.45, P<0.001; t=3.89, P<0.001; t=5.29, P<0.001). The serum levels of TSH [ (2.69±0.46) mU/ml vs. (3.06±0.65) mU/ml], FT 4 [ (10.45±1.13) pmol/L vs. (11.50±1.36) pmol/L], TPOAb [ (56.27±5.61) U/ml vs. (62.47±6.34) U/ml] and TGAb [ (81.62±8.31) U/ml vs. (91.73±9.35) U/ml] in the survival group were significantly lower than those in the death group, with statistically significant differences ( t=2.27, P=0.025; t=3.02, P=0.003; t=3.79, P<0.001; t=4.19, P<0.001). Multivariate logistic regression analysis showed that TSH ( OR=1.52, 95% CI: 1.13-2.05, P=0.006), TPOAb ( OR=1.42, 95% CI: 1.13-1.78, P=0.002) and TGAb ( OR=1.35, 95% CI: 1.05-1.73, P=0.018) were all independent factors affecting the efficacy of patients with advanced cancer treated with PD-1 inhibitors. Multivariate Cox regression analysis showed that TSH ( HR=1.42, 95% CI: 1.06-1.92, P=0.030), TPOAb ( HR=1.31, 95% CI: 1.05-1.64, P=0.018), TGAb ( HR=1.41, 95% CI: 1.09-1.83, P=0.008) and FT 4 ( HR=1.36, 95% CI: 1.02-1.81, P=0.038) were all independent factors affecting the survival of patients with advanced cancer treated with PD-1 inhibitors. Survival analysis showed that the median overall survival in the TFA-irAE occurrence group and the TFA-irAE non-occurrence group were 10.8 and 8.0 months, respectively, with a statistically significant difference ( χ2=9.53, P=0.002) . Conclusion:Although the occurrence of TFA-irAE may have less effect on the efficacy of advanced tumor patients treated with PD-1 inhibitors, it may affect the survival of patients. TSH, TPOAb and TGAb are all independent influencing factors for the efficacy of patients with advanced tumors treated with PD-1 inhibitors, while TSH, TPOAb, TGAb and FT 4 are independent influencing factors for the survival of patients with advanced tumors treated with PD-1 inhibitors.

Objective:To study the anatomy of the perforator propeller flap of superior lateral genicular artery, and to explore a surgical method and clinical application in repair of the soft tissue defect of anterolateral knee with the flap.Methods:From September 2019 to September 2021, 8 knees of 4 chilled fresh specimen of adults were studied. The perforators of the superior lateral genicular artery were observed. The length, outer diameter of the perforators, and the locations of the skin perforation were recorded. The superior lateral genicular artery perforator propeller flaps were then applied clinically to 5 patients(3 males and 2 females) with soft tissue defects of anterolateral knee. Two of the patients had combined ligament injury and(or) bone joint exposure. The age of patients ranged from 25 to 48 years old, at 33.4 years old in average. The sizes of soft tissue defects ranged from 4.0 cm×4.0 cm to 8.0 cm×5.0 cm. The sizes of perforator propeller flaps of superior lateral genicular artery were 10.0 cm×5.0 cm to 13.0 cm×6.0 cm. The superior perforating vessels of the superior lateral genicular artery were found and marked at the points of skin perforation. Preoperative contrast-enhanced ultrasound were performed to confirm the dominant perforating vessels and had the skin perforating points marked. Intraoperative CDU were further performed to confirm the points of dominant perforating vessels. Perforator propeller flaps were designed depending on the size of the anterolateral soft tissue defect, and flaps were prepared and transferred to the defect sites. Postoperative follow-ups were conducted at outpatient clinic. The survival of the flap and knee function were observed according to the Bai-ly knee scoring.Results:The anatomy showed that an average pedicle length of the superior lateral genicular artery perforator was(8.2±0.9) cm, with an average starting outer diameter at(1.1±0.2) mm. All 5 flaps survived during the follow-up that lasted for 10 to 24 months, with an average of 15.3 months. All flaps healed in 2 weeks after surgery without complications such as soft tissue infection, bone and joint infection were observed. At the last follow-up, no obvious bloated appearance of the flaps were observed. The colour and elasticity of the flaps were similar to the surrounding skin. The knee function was assessed: 4 patients were in excellent and 1 in good. The range of knee flexion and extension was from 100° to 150°. The patients were satisfied with the appearance and function of the knees.Conclusion:The size of the perforator of superior lateral genicular artery and the pedicle length are ideal. The propeller flap can be used to repair the soft tissue defect around the anterolateral knee, with satisfactory functional recovery of a knee. It is a good method to repair the soft tissue defect around anterolateral knee.

The 2023 European Society for Medical Oncology (ESMO) annual meeting reported on the research progress in the field of clinical treatment, biomarkers, and exploration of new drugs/mechanisms for renal carcinoma, which included the first phase III trial of vascular endothelial growth factor receptor-tyrosine kinase inhibitor/immune checkpoint inhibitor (VEGFR-TKI/ICI) combination in Chinese population, trials of hypoxia inducible factor-2α (hif-2α) inhibitor, programmed cell death-Ligand 1/cytotoxic T-lymphocyte-associated antigen 4 (PD-1/CTLA-4) bispecific monoclonal antibody and antibody-drug conjugate, biomarkers of peripheral blood, tissue glycan profiling and tissue protein. This article interprets and reviews important studies to help clinical treatment decisions.