Objective: Inflammatory cascade reactions play a crucial role in secondary neuronal injury in acute ischemic stroke (AIS). The aim of this study was to explore the correlations between specific serological indicators, early neurological deterioration (END), disease prognosis, and syndrome factors in AIS based on this injury mechanism. Methods: The data for this study were collected from 135 patients with AIS admitted to the emergency department of Fangshan Hospital, Beijing University of Chinese Medicine, within 24 h of onset between November 2019 and May 2021. Among these, 29 patients had complete data and experienced END. Additionally, 9 non-END patients were matched from the remaining 90 patients with complete data, resulting in a total of 38 patients for statistical analysis. Statistical methods, including logistic regression and receiver operating curves, were used to analyze the correlation between serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule-1 (ICAM-1) within 24 h of END onset, disease prognosis, and syndrome factors. Grouping criteria included END occurrence, presence of syndrome elements on the first and third day post-onset, and prognosis at 90 days post-onset. Results: All 38 cases had onset time of less than 12 h, and there were no significant differences in age, gender, and onset time between the END and non-END groups. The TNF-α serum level within 24 h of onset was not associated with the occurrence of END but was negatively correlated with all-cause mortality at 90 days [0.110; P<0.05). An elevated IL-10 serum level within 24 h of onset showed a strong negative correlation with non-disabling and good functional outcomes at 90 days post-onset (0.110; P<0.05). When the ICAM-1 serum levels exceeded 233 599.500 μg/L and 125 141.500 μg/L, respectively, the susceptibility to endogenous wind and endogenous fire on the third day of onset was 15.364 times and 6.071 times higher, respectively, than that in patients with serum levels below these thresholds. Conclusion As accessible and objective biomarkers, inflammatory serum indicators are closely associated with both disease progression and traditional Chinese medicine (TCM) syndrome elements. They enhance AIS diagnosis, assessment, and treatment and contribute to a deeper understanding of the role of TCM syndrome differentiation in AIS diagnosis and treatment.

Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

BACKGROUND:With the development of computer-aided design and computer-aided manufacturing technology,zirconia abutments with a titanium base are widely used in clinic due to its good application advantages,but there are still some problems and a lack of consensus design standards. OBJECTIVE:To review the fabrication methods of Ti-base zirconia abutment,and the effect of abutment connection,emergence design,abutment angle,and bonding on mechanical properties of Ti-base zirconia abutment. METHODS:Relevant literature published from 2010 to 2023 was searched in CNKI and PubMed databases with the search terms"zirconia abutment,titanium base"in Chinese and English,respectively.The search time limit was extended for some classical literature.The relevant literature was obtained through inclusion and exclusion criteria,and 57 eligible documents were included for review. RESULTS AND CONCLUSION:It is recommended that clinicians try to select antirotational titanium bases or rotational titanium bases with a Morse taper connection.Implants should be placed in the correct axial angulation of not more than 15° or with an inclination to the palatal side when using angled zirconia abutments.When a≥30° labial inclination is followed for implant placement,the bite force must be decreased effectively to reduce the risk of mechanical and biological complications of implants,abutments,and prostheses.Ti-base zirconia abutments with a higher gingival height should be selected,and its restorative angle should not exceed 40°.Multilink Hybrid Abutment could be the first choice for extraoral bonding of zirconia abutment to titanium bases.

Objective: To investigate the potential of conventional cranial computed tomography (CT) in assessing the early neurological deterioration(END), long-term prognosis, and traditional Chinese medicine (TCM) syndrome elements during the acute phase in patients with acute ischemic stroke (AIS). Methods: This study included 101 patients with AIS onset within 24 h in the Emergency Department of Fangshan Hospital, Beijing University of Chinese Medicine, from November 2019 to May 2021. To investigate the correlation between the relevant characteristics of the first conventional cranial CT in patients with AIS onset within 24 h and END, 90 d prognosis, and initial syndrome elements, the presence or absence of END, the 90 d prognosis (non-disabling outcome or functionally independent outcome), and the establishment of syndrome elements (internal fire, phlegm-dampness, blood stasis, qi deficiency, yin deficiency) were used as dependent variables and grouping criteria. Results: This study included 61 males and 40 females, with an age of (64.43±10.56) years. The time from onset to conventional cranial CT examination was 3.50 (1.50, 9.75) h. Among the patients, there were 70 cases (69.3%) of mild AIS, 30 cases (29.7%) of moderate AIS, and one case (1.0%) of severe AIS. Fifteen patients (14.9%) received intravenous thrombolysis. Among the 101 patients, six syndrome elements were observed within 24 h of onset: internal wind in 101 cases (100.0%), internal fire in 58 cases (57.4%), phlegm-dampness in 60 cases (59.4%), blood stasis in 67 cases (66.3%), qi deficiency in 39 cases (38.6%), and yin deficiency in 23 cases (22.8%). The incidence of END was higher in patients with lesions in the contralateral cerebral hemisphere to the affected limb (32.9%) than in those without such lesions (10.7%), showing a strong positive correlation with END occurrence (OR=4.082, P = 0.026). The incidence of END was higher in patients with lesions in the basal ganglia region (33.3%) and the carotid system blood supply area (32.8%) than in those without lesions in the basal ganglia region (15.8%) and the carotid system territory (14.7%), showing moderate positive correlations with END occurrence (OR=2.667, P =0.047; OR=2.836, P=0.044). The proportion of non-disabling outcomes was lower among patients with white matter degeneration (30.8%) and lesions in the contralateral cerebral hemisphere to the affected limb (52.1%) than in those without white matter degeneration (63.6%) and without such lesions in the contralateral cerebral hemisphere to the affected limb (78.6%), both showing strong negative correlations with the occurrence of non-disabling outcomes (OR=0.254, P=0.034; OR=0.296, P=0.015). Similarly, the proportion of functionally independent outcomes was lower among individuals with white matter degeneration (30.8%) and lesions in the contralateral cerebral hemisphere to the affected limb (64.4%) than in those without white matter degeneration (77.3%) and without such lesions in the contralateral cerebral hemisphere to the affected limb (89.3%), both also showing strong negative correlations with the occurrence of functionally independent outcomes (OR=0.131, P=0.001; OR=0.217, P=0.014). The incidence rates of internal fire, blood stasis, and yin deficiency syndrome elements were 66.7%, 73.0%, and 30.2%, respectively, among patients with lesions in the basal ganglia region, compared to 42.1%, 55.3%, and 10.5% among those without lesions in this region. The presence of lesions in the basal ganglia region showed moderate to strong positive correlations with internal fire and yin deficiency syndrome elements (OR=2.750, P=0.016; OR=3.670, P=0.028). Patients with lesions in the centrum semiovale and corona radiata regions (66.7%) had a higher incidence of qi deficiency than those without lesions in this region (33.7%), showing a strong positive correlation with the occurrence of qi deficiency (OR=3.931, P=0.022). No CT characteristics were found to be correlated with phlegm-dampness syndrome elements. Conclusion The first cranial CT in patients with AIS has potential application value in predicting disease progression, assessing prognosis, and diagnosing syndromes, which can provide physicians with diagnostic and treatment decisions to improve the long-term prognosis of patients with AIS.

OBJECTIVE To establish a method for determining the contents of clopidogrel （CLP）， clopidogrel carboxylate （CLP-C）， clopidogrel acyl-β-D-glucuronide （CLP-G） and contents of clopidogrel active metabolite （CAM） in rat plasma， and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile （both containing 0.1% formic acid） in a gradient elution. The flow rate was 0.4 mL/min， and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 （for CLP）， m/z 308.1→197.9 （for CLP-C）， m/z 322.1→154.8 （for CLP-G）， m/z 504.1→154.9 [for racemic CAM derivative （CAMD）]. Six rats were administered a single intragastric dose of CLP （10 mg/kg）. Blood samples were collected before medication and at 0.08， 0.33， 0.66， 1， 2， 4， 6， 10， 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP， CLP-C and CAMD were 0.08-20.00， 205.00-8 000.00， and 0.04-25.00 ng/mL， respectively （r≥0.990）. The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%， and the relative errors for accuracy ranged from －11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%， meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that， following a single intagastric administration of CLP in rats， the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve （AUC0-35 h） and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP， though it had a shorter half-life （2.53 h）. The inactive metabolite CLP-C exhibited the highest exposure level， but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM， and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites， and revealed their pharmacokinetic characteristics in rats. Specifically， the parent drug CLP was rapidly eliminated， while the inactive metabolites CLP-C and CLP-G exhibited long half-lives， and active metabolite CAM displayed a transient exposure pattern.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

The statement of"qi transformation leading to the removal of pathogenic dampness"was recorded in Wen Bing Tiao Bian(Analysis on Epidemic Febrile Diseases)written by the Qing Dynasty physician WU Ju-Tong.Dampness in the triple energizer is caused by the dysfunction of qi transformation,and the treatment of dampness must be based on the activation of qi movement and focused on the promotion of qi movement and the restoration of the qi transformation in the triple energizer.For the treatment of dampness attack in the upper energizer,therapies of dispersing lung to smooth qi and resolving dampness to relieve the obstruction are recommended.For the treatment of dampness obstruction in the middle energizer,therapy of activating spleen qi by strengthening spleen and moving qi is stressed for helping the removal of dampness and for the eradication of the source of dampness.For the treatment of dampness stagnation in the lower energizer,therapy of draining dampness with sweet-light medicines and activating yang can be used according to the illness status.The three methods of treating dampness,namely dispersing the upper energizer,activating the middle energizer and draining the lower energizer,all embody the mechanism of"qi transformation leading to the removal of pathogenic dampness",and the therapies of dispersing lung with light medicines,inducing perspiration by opening striated layer,eliminating dampness with aromatics and draining dampness with sweet-light medicines should be used in accordance with the syndromes.The elucidation of the academic thoughts of"qi transformation leading to the removal of pathogenic dampness"can provide theoretical reference for the fundamental research of dampness syndrome and clinical application of therapies for resolving dampness in Chinese medicine.

Objective:This study aims to investigate the inner experiences of cancer patients when confronting financial toxicity through a Meta-analytical approach. The goal is to provide evidence-based insights and theoretical references for clinical healthcare professionals to fully understand the feelings and experiences associated with financial toxicity in cancer patients, thereby laying a foundation for targeted interventional measures.Methods:A computerized search was conducted across databases including CINAHL, PubMed, PsycINFO, Embase, Scopus, Web of Science, CNKI, WanFang, VIP, Sinomed and other databases, collecting qualitative studies related to the inner experience of financial toxicity among cancer patients, up until April 12, 2023. Quality appraisal of the included literature was carried out according to JBI′s standards for qualitative research, and results were synthesized using Meta-aggregation methods.Results:Twenty-three studies were included, from which 82 specific outcomes were extracted. These were categorized into 11 new thematic groups and ultimately synthesized into four integrated findings: the impact of objective costs, subjective burden, and unreasonable expectations; diverse cognitive attitudes and management coping strategies; multiple pressures and challenges on patients and their families; and the articulation of needs and perceptions of beneficial growth.Conclusions:Healthcare professionals should pay attention to the financial toxicity issues that patients face at the initial stage of cancer diagnosis. Timely communication about economic issues between patients and healthcare providers is essential to help patients have a preliminary understanding of the impending financial toxicity at the onset of the disease. A comprehensive intervention that emphasizes different aspects of objective and subjective financial toxicity, coupled with multi-dimensional mitigation strategies, can promote active coping in patients, enhance familial emotional and financial support to overcome challenges together, and prioritize patients′ needs and expectations to guide them towards reinforcing positive experiences and minimizing the impact of financial toxicity.

BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.Static exercise can effectively improve skeletal muscle insulin resistance,but the mechanism remains unclear. OBJECTIVE:To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase(PI3K)/protein kinase B(AKT)/glucose transporter(GLUT4)signaling pathway. METHODS:After 1 week of adaptive feeding,7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet,while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection.Twenty-four mice were successfully modeled and they were randomly divided into model group(n=8),metformin group(n=8)and static exercise group(n=8),which continued to be fed high-fat diet.The metformin group was given 200 mg/kg metformin dissolved in normal saline(2 ml/kg)by gavage,once a day,for 6 weeks.The static exercise group was given normal saline daily by gavage and carried out static exercise,30 minutes a day,6 days per week.The model group was given the same dose of normal saline daily by gavage without exercise intervention.After the intervention,the fasting blood glucose of each group was detected,the intraperitoneal glucose tolerance test was performed,and the area under the glycemic curve was calculated.Glycosylated hemoglobin,serum insulin,insulin resistance index were detected by ELISA.Total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein were detected using biochemical methods.The mRNA expression levels of PI3K,AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR.Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining,and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION:Compared with the blank group,fasting blood glucose,glycosylated hemoglobin,area under the glycemic curve,insulin resistance index,total cholesterol,triglyceride and low-density lipoprotein levels were significantly increased in the model group(P<0.01,P<0.05).Whereas,these indicators were significantly lower in the static exercise and metformin group than the model group(P<0.01,P<0.05).Compared with the blank group,serum insulin and high-density lipoprotein levels were significantly declined in the model group(P<0.01)and the mRNA expression of PI3K,AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced(P<0.01).These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group(P<0.01).Compared with the blank group,the muscle fibers in the model group were disordered,and the muscle cells atrophied and the muscle fiber gap widened.The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group(P<0.01).Compared with the model group,atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group,and the cross-sectional area of muscle fiber was significantly increased in both groups(P<0.01).These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K,AKT and GLUT4 mRNA in skeletal muscle tissue,thereby improving the morphology and function of skeletal muscle tissue,alleviating insulin resistance and regulating glucose homeostasis.

BACKGROUND:With the increasing demand for edentulous jaw restoration,"All-on-4"concept is widely used.The load transfer mode of implant is different from that of natural tooth.The three-dimensional finite element analysis can study the stress distribution of implants and surrounding bone tissues under functional loading.On this basis,it provides research methods for finding suitable implant materials,optimizing implant geometry,and designing clinical surgical protocols. OBJECTIVE:To review researches related to three-dimensional finite element analysis in"All-on-4"concept. METHODS:Relevant literature published from 2003 to 2023 was searched in CNKI and PubMed databases with the search terms of"finite element method;All-on-4;edentulous;biomechanics"in Chinese and English.Finally,65 articles were included for review. RESULTS AND CONCLUSION:(1)In the case of insufficient horizontal bone mass,we can choose to apply narrow diameter implants,but we need to pay attention to the effect of the presence of the cantilever on the stress distribution and reduce the risk of failure.(2)The"All-on-4"concept reduces the stress distribution of bone by tilting the distal middle implant,but the ideal angle of the distal implant tilt in different jaw types requires further study.(3)The presence of cantilevers increases the risk of implant failure,and keeping the cantilever length/AP distance ratio at 0.9 helps to minimize mechanical complications.(4)When a framework is made of a material with a lower elastic modulus,the stress on the framework itself will be smaller,but it will increase the stress on the implant,prosthetic screw,abutment and peri-implant bone.On the contrary,when a material with a higher elastic modulus is used,it can reduce the stress on the prosthetic components,implants and peri-implant bone in the restoration,but the stress on the framework itself is higher.(5)The"All-on-4"concept allows for a better mechanistic balance,but requires the development of a long-term,effective treatment program that is tailored to the patient's specific situation.(6)Proper occlusal scheme is the key to the success of implant treatment,and there is no difference between canine-guide occlusion and group function occlusion in terms of the longevity of the restoration.However,there are many factors that influence occlusal design,and further in vitro experiments as well as a number of clinical studies are needed to explore the ideal occlusal design of the"All-on-4".