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Guided by the theory of "kidney generates marrow", the study elaborates the viewpoint that the route of Yin Heel Channel (阴跷脉) is consistent with the "kidney-marrow-brain" axis from the perspective of the circulation of the meridians and the relationship between the zang-fu organs. Accordingly, it is believed that disease of Yin Heel Channel and dysfunction of the "kidney-marrow-brain" axis are the core pathogenesis of children enuresis, and it is elaborated from the following three major aspects, firstly, insufficient kidney essence, dysfunction of the "kidney-marrow-brain" axis, secondly, disease of Yin Heel Channel and deficiency and cold in lower jiao, and thirdly, disease of Yin Heel Channel and loss of nourishment of Chong Vessel. It is proposed to use the mode of "firstly needle, secondly moxibustion, and lastly consolidation" to treat children enuresis. Needle is to adjust yin and yang, warm yang and tonify kidney, and wake up the brain and open the orifices. The acupoints in Yin Heel Channel such as Zhaohai (KI 6), Jiaoxin (KI 8) and confluence points of the eight extraordinary vessels such as Waiguan (TE 5), Zulinqi (GB 41) are used, together with Baihui (GV 20), Yintang (EX-HN 3), Guanyuan (CV 4), Qixue (KI 13), Dazhong (KI 4). Moxibustion is to reinforce healthy qi and warm yang, bank up the root and consolidate the original qi by moxibustion at Shenque (CV 8), Mingmen (GV 4), and Xuanshu (GV 5). Consolidation is to use acupoints application to consolidate the therapeutic effect, and Guanyuan (CV 4) & Pangguangshu (BL 28), Qihai (CV 6) & Zhishi (BL 52), and Shenque (CV 8) & Ciliao (BL 32) are commonly used as the three groups of acupoints to warm the kidney and stop collapse, regulate and tonify the qi and blood.
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Tripterygium wilfordii polyglycosides are one of the most commonly used Tripterygium wilfordii preparations, which have anti-inflammatory and immune-regulating effects. Their unique therapeutic effect on some autoimmune diseases and kidney diseases is almost irreplaceable by other similar drugs, but the possible reproductive damage is the bottleneck that hinders their clinical application. In clinical use, female patients often suffer from menstrual cycle disorders, decreased menstrual flow, even amenorrhea, infertility, and other symptoms, and the main toxic mechanism lies in damaging the reproductive and endocrine functions of the ovary and inhibiting the growth and development of follicles. Therefore, it is particularly necessary to understand the toxic and side effects of Tripterygium wilfordii polyglycosides on female reproduction and master the detoxification methods during clinical use. However, there is no clear solution to these problems. According to the theory of traditional Chinese medicine, "kidney governs reproduction", and the relationship between kidney Yin, kidney essence, and female ovum is close. Therefore, by considering that the damage to the reproductive system caused by Tripterygium wilfordii polyglycosides belongs to the category of kidney deficiency, Yin damage, and essence deficiency, the "strengthening kidney Yin" method is proposed. It points out that the reproductive toxicity damage of Tripterygium wilfordii polyglycosides on the female can be effectively alleviated by tonifying kidney and Yin essence in clinical use. The relevant research on traditional Chinese medicine, classical prescription, test prescription, and acupuncture is summarized to verify the necessity of the "strengthening kidney Yin" method, so as to provide a theoretical basis for the safe and rational clinical use of Tripterygium wilfordii.
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BACKGROUND@#Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.@*METHODS@#Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.@*RESULTS@#The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients ( rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% ( rs = -0.445, P = 0.003) and NLR ( rs = -0.436, P = 0.003), while positively associated with Lym% ( rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.@*CONCLUSIONS@#ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.
Subject(s)
Humans , Amyotrophic Lateral Sclerosis/microbiology , Feces/microbiology , Microbiota/genetics , Gastrointestinal Microbiome/genetics , Bacteria/genetics , RNA, Ribosomal, 16S/geneticsABSTRACT
Objective:To analyze the correlation between the expressions of human epidermal growth factor receptor 2(HER2)and carbohydrate antigen 153(CA153)and the technical parameter of acoustic palpation tissue imaging quantification(VTIQ)in patients with breast cancer.Methods:A total of 80 female patients with breast cancer admitted to The Third People's Hospital of Hefei from May 2018 to May 2020 were selected,including 14 cases at WHO stage Ⅰ,22 cases at WHO stage Ⅱ,31 cases at WHO stage Ⅲ and 13 cases at WHO stage Ⅳ.Another 53 female patients with benign breast diseases who were treated during the same period were selected as controls.At first,all patients underwent routine ultrasound examination,and then they entered the ultrasound VTIQ imaging mode to obtain the mean value of shear wave velocity(SWV).An immunohistochemistry was used to detect HER2 expressions in breast tissues,and Roche E411 electrochemiluminescence immunoassay analyzer was used to detect serum CA153 levels of them.Pearson method was used to analyze the correlation between serum CA153 levels and SWV mean values in patients with breast cancer.Results:Compared with benign patients,the SWV mean value of VTIQ technical parameter,serum CA153 level and HRR2 positive expression rate in patients with breast cancer were significantly higher,and the difference was statistically significant(F=39.107,78.353,P<0.05),respectively.Compared with patients at stages Ⅰ + Ⅱ of breast cancer,the SWV mean value of VTIQ technical parameter,serum CA153 level and HRR2 positive expression rate of patients at stages Ⅲ and Ⅳ of breast cancer significantly increased(t=2.685,3.556,8.326,10.455,P<0.05),respectively.Compared with patients at stage Ⅲ of breast cancer,the SWV mean value of VTIQ technical parameters,serum CA153 level and HRR2 positive expression rate of patients at Ⅳ stage of breast cancer were significantly higher(t=4.632,8.659,P<0.05),respectively.Compared with the SWV mean value of patients with HER2 negative expression of breast cancer,that of patients with HER2 positive expression of breast cancer was significantly higher(x2=59.751,P<0.05).There was a positive correlation between serum CA153 levels and SWV mean values in patients with breast cancer(r=0.501,P<0.05).Conclusion:The SWV mean value of VTIQ parameters is closely related to the expression levels of biomarkers HER2 and CA153 in patients with breast cancer.
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This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.
Subject(s)
Rats , Male , Animals , Diabetic Nephropathies/genetics , Interleukin-18/metabolism , Glycosides/pharmacology , Tripterygium , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Rats, Sprague-Dawley , Caspase 1/metabolism , Pyroptosis , Uridine Triphosphate/pharmacology , Kidney , Valsartan/pharmacology , RNA, Messenger/metabolism , Diabetes MellitusABSTRACT
Objective: To investigate the clinical characteristics of children with allergic diseases suffering from SARS-CoV-2 Omicron variant strains. Methods: This was a cross-sectional study. A total of 43 pediatric patients with allergic diseases infected by SARS-CoV-2 from April 25, 2022 to June 8, 2022 in Shanghai Jiao Tong University School of Medicine were selected as the allergic disease group, while 114 cases without underlying diseases and 16 cases with other underlying diseases were selected as control groups diagnosed at the same period. Clinical data including clinical features, laboratory tests, duration of hospitalization, and the time to negative turn of novel coronavirus nucleic acid were collected and analysed. Kruskal-Wallis H test, chi-square test or Fisher exact test were used for comparison among three groups. Results: Among the 43 patients with allergic diseases, 28 were males and 15 were females, with an age of 4.4 (2.1, 8.2) years on admission, including 32 mild cases and 11 common cases. The allergic disease group included 20 cases (46.5%) of atopic dermatitis and eczema, followed by 14 cases (32.6%) of rhinitis, 8 cases (18.6%) of food allergies, 7 cases (16.3%) of asthma, 4 cases (9.3%) of allergic conjunctivitis and 2 cases (4.7%) of drug allergy. Among the 114 cases without underlying diseases, 57 were males and 57 were females, with an age of 2.8 (1.2, 5.6) years on admission, including 93 mild cases and 21 common cases. Among the 16 cases with other underlying diseases, 9 were males and 7 were females, with an age of 3.0 (2.6, 10.8) years on admission, including 13 cases mild and 3 cases common cases. Children with allergic diseases had higher frequency of sore throat and vomiting than those without underlying diseases (10 cases (23.3%) vs.9 cases (7.9%), 14 cases (32.6%) vs. 11 cases (9.6%), χ²=6.93, 12.24, both P<0.05). The lymphocyte count of patients with allergic disease was lower than those without underlying disease (1.1 (0.7,1.7)×109 vs. 1.6 (1.1,2.7)×109/L, H=-28.00,P=0.005). There were no significant differences in age, gender, typing of SARS-CoV-2, the duration of hospitalization, cycle threshold values of SARS-CoV-2 and the time to negative turn of novel coronavirus nucleic acid among the three groups (all P>0.05). Conclusions: Children with allergic diseases may suffer from sore throat and vomiting more frequently when infected with SARS-CoV-2 Omicron variant. The combination of allergic diseases hardly influenced the disease course of SARS-CoV-2 in children.
Subject(s)
Male , Female , Humans , Child , SARS-CoV-2 , Cross-Sectional Studies , COVID-19 , China/epidemiology , Food Hypersensitivity , PharyngitisABSTRACT
Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Subject(s)
Humans , Mesothelioma, Malignant , Prognosis , Nomograms , Retrospective Studies , Proportional Hazards ModelsABSTRACT
OBJECTIVE@#To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy.@*METHODS@#We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups.@*RESULTS@#After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05).@*CONCLUSION@#DEX can not reduce the incidence of AKI or CKD after LRN.
Subject(s)
Humans , Dexmedetomidine , Incidence , Propensity Score , Renal Insufficiency, Chronic/epidemiology , Kidney Neoplasms/surgery , Nephrectomy/adverse effects , Laparoscopy/adverse effects , Acute Kidney Injury/prevention & control , Retrospective StudiesABSTRACT
Objective:To investigate the correlation between the expression level of serum exosome miR-29C and postoperative cognitive dysfunction (POCD) in elderly patients undergoing surgery.Methods:A total of 119 elderly patients who underwent elective spinal surgery in the Second Hospital of Shanxi Medical University from January 2021 to January 2022 were selected and scored on the Montreal Cognitive Assessment (MoCA) Scale 1 day before surgery and 1, 7 and 21 days after surgery. The selected patients were divided into POCD group (51 cases) and non-POCD group (68 cases) according to whether the MoCA Scale score decreased ≥2 points 1 day before surgery and 1 day after surgery. S100-β, neuron-specific enolase (NSE) levels and serum exosome miR-29C expression levels were detected and analyzed in all patients 1 day before and 1 day after surgery. Pearson correlation analysis showed the correlation between MoCA Scale score and S100-β, NSE and miR-29C. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of S100-β, NSE and miR-29C for POCD occurrence in elderly patients undergoing surgery.Results:The score of MoCA Scale in POCD group were significantly decreased 1, 7 and 21 days after surgery compared with 1 day before surgery (all P<0.05), while the score of MoCA Scale in non-POCD group were significantly decreased only 1 day after surgery compared with 1 day before surgery ( P<0.05). The levels of S100-β and NSE and the expression level of serum exosome miR-29C in 2 groups were significantly increased 1 day after surgery compared with 1 day before surgery (all P<0.05). Moreover, the levels of S100-β and NSE and the expression level of serum exosome miR-29C in POCD group were significantly higher than those in non-POCD group 1 day after surgery (all P<0.05). There was a negative correlation between the MoCA Scale score and the expression level of serum exosome miR-29C 1 day after surgery in the POCD group ( P<0.05). ROC curve analysis showed that the expression levels of NSE, S100-β and exosome miR-29C 1 day after surgery predicted the risk of POCD in elderly surgical patients with area under the curve (AUC) of 0.891, 0.908 and 0.918, respectively. Conclusions:The occurrence of POCD in elderly patients with surgery is related to the increase of the expression level of serum exosome miR-29C, and the expression level of serum exosome miR-29C is negatively correlated with MoCA Scale score. Early monitoring of the miR-29C expression level can provide a basis for the occurrence and development of postoperative POCD in elderly patients, disease diagnosis and clinical intervention.
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Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.
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Objective:To investigate the predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor (GIST). Methods:From March 2014 to June 2020, the 18F-FDG PET/CT imaging and surgical pathological data of 35 patients with GIST (27 males, 8 females; age 44-84 years) from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and Zhongnan Hospital of Wuhan University were analyzed retrospectively. Patients were divided into ring-shaped uptake group and other uptake patterns group according to 18F-FDG PET/CT image feature. Fisher′s exact test was used to analyze the differences of tumor necrosis and National Institutes of Health (NIH) risk classification (short for NIH classification) between different image feature groups. Mann-Whitney U test was used to analyze the differences of SUV max , metabolic parameters at different thresholds (2.5, 40%, 50%) of SUV max (metabolic tumor volume (MTV; MTV 2.5, MTV 40%, MTV 50%) and total lesion glycolysis (TLG; TLG 2.5, TLG 40%, TLG 50%)) between different clinicopathological features (lesion location, tumor diameter, mitotic count, Ki-67, necrosis, image feature, NIH classification) groups. Spearman rank correlation analysis was used to explore the correlation between clinicopathological features and metabolic parameters. ROC curve analysis was used to distinguish NIH classification of different metabolic parameters. Delong test was used to compared differences between different AUCs. Results:Of 35 GIST patients, 11(31.4%) were ring-shaped uptake and 24(68.6%) were other uptake patterns, and the differences of necrosis (7/11 vs 12.5%(3/24); P=0.004) and NIH classification (11/11 vs 25.0%(6/24); P<0.001) between the two groups were significant. There were significant differences of metabolic parameters between different groups of tumor diameter, mitotic count, necrosis, image feature, NIH classification ( z values: from -4.70 to -2.09, all P<0.05), while there were no significant differences of Ki-67 ( z values: from -0.83 to -0.71, all P>0.05). Metabolic parameters were correlated with mitotic count, tumor diameter, necrosis, image feature and NIH classification ( rs values: 0.36-0.81, all P<0.05), while was not correlated with Ki-67 ( rs values: 0.12-0.14, all P>0.05). The differences of AUCs between SUV max and MTV 2.5, TLG 2.5, TLG 40%, TLG 50%were significant (0.752, 0.856, 0.856, 0.882, 0.886; z values: 1.96-2.12, all P<0.05). Conclusions:The NIH classification of GIST with ring-shaped uptake on 18F-FDG PET/CT is higher and more prone to necrosis. The 18F-FDG PET/CT metabolic parameters based on different thresholds of SUV max have certain significance for the prediction of NIH classification of GIST, and may be superior to SUV max.
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The treatment of persistent/recurrent and metastatic thyroid cancer and medullary thyroid cancer has made significant progress through the use of molecule-targeted therapy. While this approach has shown promise in improving patient outcomes and clinical symptoms, it also carries potential risks. The primary focus and challenge of targeted therapy is to optimize benefits while managing risks within predetermined thresholds. This review examines current targeted treatment practices in thyroid cancer and investigates the correlation between the timing of targeted therapy initiation and the patient benefits, aiming to lay the groundwork for subsequent research.
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Dexmedetomidine is a highly selective α2 adrenergic receptor agonist,exerting anti-sympathetic,sedative,analgesic and anti-anxiety effects,with minimal impact on respiration.In recent years,dexmedetomidine has been widely used in clinical anesthesia,perioperative treatment,and intensive care.Organ-protection is an important focus of anesthesia and perioperative medicine,with clinical significance in reducing complications and improving short-and long-term outcomes.Increasing clinical evidence and basic research have shown that the application of dexmedetomidine could protect the heart,brain,lung,kidney,liver,gastrointestinal tract and other important organs.The mechanism may be related to dexmedetomidine's effects of anti-inflammation,anti-oxidation,anti-apoptosis,and autophagy regulation.From our perspectives,clinical use should follow the principle of individualization,and the dose should be adjusted in time according to patients'responses,so as to avoid adverse reactions such as hypotension and bradycardia while protecting the organs.Moreover,more strictly designed clinical studies and in-depth mechanistic investigations are needed for the optimal dexmedetomidine therapy and better organ protection during the perioperative course.In order to facilitate better understanding of clinicians,this paper reviews the organ-protective effects and underlying mechanisms of dexmedetomidine.
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Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.
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Objective To explore the regulatory effect of miR-26b-5p on PI3K/PIP3 signaling path-way and its effect on L-type calcium channel of atrial cardiomyocytes in rats with ischemic ar-rhythmia.Methods A total of 72 SD rats were randomly divided into sham operation group,mod-el group,LY294002 group,negative control group,overexpression group and combination group,with 12 rats in each group.In 24 h after corresponding intervention,rat model of ischemic arrhyth-mia was established in the other groups except the sham operation group(only thoracotomy but without ligation).During the modeling process,arrhythmia indexes were detected in each group,and Curtis-Walker scoring was used for arrhythmia score.Fluorescence quantitative PCR was em-ployed to detect the expression of miR-26b-5p in atrial myocardiocytes,whole-cell patch-clamp technique was used to record the ICa-L of atrial myocardiocytes,and Western blotting was applied to measure the expression of CACNA1C,calmodulin and PI3K/PIP3 pathway related proteins.Re-sults Compared with the model group,the number of left ventricular preventricular contrac-tions,duration of ventricular tachycardia,duration of ventricular fibrillation,arrhythmia score,ab-solute value of ICa-L peak density of atrial myocardiocytes,and expression levels of CACNA1C and calmodulin were significantly increased,and the levels of miR-26b-5p,p-PI3K,PIP3 and p-Akt were obviously decreased in the LY294002 group(P<0.05).While the overexpression group had decreased number of left ventricular preventricular contractions,shorter duration of ventricular tachycardia,shorter duration of ventricular fibrillation,lower arrhythmia score,reduced absolute value of ICa-L peak density,and lower expression levels of CACNA1C and calmodulin,and in-creased levels of miR-26b-5p,p-PI3K,PIP3 and p-Akt than the model group(P<0.05).The number of left ventricular preventricular contractions,duration of ventricular tachycardia,dura-tion of ventricular fibrillation,arrhythmia score,absolute value of ICa-L peak density and expres-sion levels of CACNA1C and calmodulin were significantly increased,and the expression of p-PI3K,PIP3 and p-Akt were obviously decreased(0.82±0.08 vs 1.09±0.11,0.91±0.09 vs 1.17± 0.11,0.94±0.09 vs 1.20±0.12,P<0.05)in the combination group than the overexpression group.Conclusion Overexpression of miR-26b-5p may block the L-type calcium channel in atrial myocardiocytes in ischemic arrhythmia rats by activating PI3K/PIP3 related signaling pathway,and thus improve the performance of arrhythmia in rats.
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Objective To explore the role of NLRP3/Caspase-3 in myocardial apoptosis induced by ischemia/reperfusion(IR)injury and its effect on myocardiocyte autophagy in rats.Methods A total of 60 SPF-grade male rats were randomly divided into sham operation,model,and nimodip-ine treatment groups,with 20 rats in each group.Rat model of myocardial IR injury was estab-lished in the rats of the two latter groups.Cardiac function was assessed,and the levels of myocar-dial enzymes and cytokines were measured.Additionally,myocardial pathological changes were de-tected using HE staining.Furthermore,flow cytometry was utilized to determine the apoptotic rate of myocardiocytes,and the autophagosomes were counted under transmission electron micro-scope.Moreover,the expression of NLRP3 and Caspase-3 was measured using RT-PCR and West-ern blotting.Results Significant differences were observed in left ventricular end diastolic pres-sure,left ventricular systolic pressure,maximal rate of rise and fall in left ventricular pressure,ap-optotic rate of myocardial cells,and levels of TNF-α,IL-6,CK,AST and LDH in the three groups(P<0.01).Notably,both the model group and nimodipine treatment group exhibited significantly higher autophagosome than the sham operation group(10.55±1.87 and 6.32±1.43 vs 3.45±0.67 units,P<0.01),and the nimodipine group displayed a significantly lower autophagosome count than the model group(P<0.01).The mRNA and protein levels of NLRP3 and Caspase-3 were notably higher in the model group and nimodipine group than the sham operation group(P<0.01),and in the model group than the nimodipine group(P<0.01).Conclusion Myocardial IR injury in rats can increase myocardiocyte apoptosis,reduce cardiac function,induce inflammatory response,and enhance autophagosome formation,which is related to the abnormal high expression of NLRP3/Caspase-3.
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OBJECTIVE To evaluate the cost-effectiveness of pembrolizumab combined with chemotherapy versus placebo combined with chemotherapy in the first-line treatment of advanced or unresectable biliary tract carcinoma (BTC) from the perspective of China’s health system. METHODS A partitioned survival model was constructed based on the KEYNOTE-966 study data. The simulation period was 21 days, and the simulation time was the patient’s whole life. Using quality-adjusted life year (QALY) as the output indicator, the cost-utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the results of the basic analysis, and to explore the cost-effectiveness under the scenario of drug donation scheme. RESULTS The basic analysis showed that both the cost and effectiveness of the pembrolizumab group were higher than those of the placebo group, and the incremental cost-effectiveness ratio (ICER) was 3 909 359.78 yuan/QALY, which was higher than the willingness-to-pay (WTP) threshold of 3 times 2022 gross domestic product (GDP) per capita (257 094 yuan), indicating no cost-effectiveness. The results of univariate sensitivity analysis showed that the utility discount rate, the utility value of progression-free survival (PFS) status, the cost discount rate, and the cost of pembrolizumab had a great influence on ICER. Probabilistic sensitivity analysis verified the robustness of the results of basic analysis, and concluded that when the WTP threshold was greater than 1 500 000 yuan/QALY, the pembrolizumab group became cost-effective. The results of the scenario analysis showed that considering the drug donation scheme of pembrolizumab for low-income people, although its treatment cost was significantly reduced, it was still not cost-effective. CONCLUSIONS At the WTP threshold of 3 times China’s GDP per capita in 2022, pembrolizumab combined with chemotherapy is not cost-effective compared with placebo combined with chemotherapy for advanced or unresectable BTC.
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ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets (TWPT) in the prevention and treatment of kidney injury in diabetic nephropathy (DN) through the nuclear factor of activated T-cells 2(NFAT2)/cyclooxygenase-2(COX-2) pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group (n=8) and an experimental group (n=34) after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin (STZ) following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated, the remaining 24 model rats were randomly divided into model group, valsartan (8.33 mg·kg-1·d-1) group, and TWPT (5 mg·kg-1·d-1) group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks, body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta, and then the rats were sacrificed for sampling. Biochemical indicators, such as serum blood urea nitrogen (BUN), serum creatinine (SCr), alanine aminotransferase (ALT), blood lipid, blood glucose, and 24-hour urine total protein (24 h UTP), were determined. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay (ELISA) was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)were adopted to detect NFAT2, COX-2 protein and mRNA expression in kidney tissues, respectively. ResultCompared with the normal group, the model group showed elevated 24 h UTP, BUN, SCr, CHO, TG, and FBG, increased serum NFAT2 and COX-2 production and expression (P<0.01), and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). In addition, the pathology of the kidney showed enlarged glomeruli, mild proliferation of mesangial cells, and widened mesangial stroma. Compared with the model group, the TWPT group showed decreased 24 h UTP, BUN, SCr, CHO, TG, and FBG (P<0.05,P<0.01), basically normal glomerular morphology, decreased expression of serum NFAT2 and COX-2 (P<0.01), and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues (P<0.01). ConclusionTWPT can alleviate 24 h UTP in DN model rats, protect renal function, and improve renal pathology, and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.
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ObjectiveDirected differentiation of human induced pluripotent stem cells (hiPSCs) into spinal cord γ-aminobutyric acid (GABA)-ergic progenitor cells were implanted into an decellularized optical nerve (DON) bioscaffold to construct a hiPSC-derived inhibitory neural network tissue with synaptic activities. This study aimed to provide a novel stem cell-based tissue engineering product for the study and the repair of central nervous system injury. MethodsThe combination of stepwise directional induction and tissue engineering technology was applied in this study. After hiPSCs were directionally induced into human neural progenitor cells (hNPCs) in vitro, they were seeded into a DON for three-dimensional culture, allowing further differentiation into inhibitory GABAergic neurons under the specific neuronal induction environment. Transmission electron microscopy and whole cell patch clamp technique were used to detect whether the hiPSCs differentiated neurons could form synapse-like structures and whether these neurons had spontaneous inhibitory postsynaptic currents, respectively, in order to validate that the hiPSC-derived neurons would form neural networks with synaptic transmission potentials from a structural and functional perspective. ResultsThe inhibitory neurons of GABAergic phenotype were successfully induced from hiPSCs in vitro, and maintained good viability after 28 days of culture. With the transmission electron microscopy, it was observed that many cell junctions were formed between hiPSC-derived neural cells in the three-dimensional materials, some of which presented a synapse- like structure, manifested as the slight thickness of cell membrane and a small number of vesicles within one side of the cell junctions, the typical structure of a presynatic component, and focal thickness of the membrane of the other side of the cell junctions, a typical structure of a postsynaptic component. According to whole-cell patch-clamp recording, the hiPSC-derived neurons had the capability to generate action potentials and spontaneous inhibitory postsynaptic currents were recorded in this biotissue. ConclusionsThe results of this study indicated that hiPSCs can be induced to differentiate into GABAergic progenitor cells in vitro and can successfully construct iPSC-derived inhibitory neural network tissue with synaptic transmission after implanted into a DON for three-dimensional culture. This study would provide a novel neural network tissue for future research and treatment of central nervous system injury by stem cell tissue engineering technology.
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Objective To establish a risk prediction model,and to observe its value for predicting retained cesarean scar pregnancy(CSP)after ultrasound-guided curettage.Methods Data of 401 CSP patients who received ultrasound-guided curettage were retrospectively analyzed.The patients were randomly divided into training set(n=264)or validation set(n=137)at a ratio of 7:3.According to whether there was retained CSP at the lower segmental scar of uterine after ultrasound-guided curettage,the patients were divided into retained group or non-retained group.The variables with the biggest predictive value for retained CSP after ultrasound-guided curettage were selected with LASSO regression,and the independent risk factors were screened using multivariate logistic regression,and then a nomogram model was established.Results The results of LASSO regression and multivariate logistic regression indicated that embedded depth of gestational sac in cesarean scar more than 1.13 cm,convexity of gestational sac,rich blood supply(Adler degree Ⅱ-Ⅲ),and pre-curettage serum β-human chorionic gonadotropin(HCG)more than 33 063.50 U/L were all independent risk factors for retained CSP after curettage(all P<0.05).The calibration curve of nomogram predictive model established based on the above indexes was basically consistent with the ideal curve,and the model had good clinical benefits.Conclusion The established nomogram predictive model had good predictive ability for retained CSP after curettage.