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Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E2-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.
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Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.
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Objective:To discuss the effect of downregulating the proline-rich protein 11(PRR11)expression on drug resistance of the esophageal cancer drug resistant cells,and to clarify the related mechanism.Methods:The drug resistant cells EC9706/cisplatin(DDP)were established by incrementally stimulating the human esophageal cancer EC9706 cells with the increasing concentrations of DDP.The drug sensitivity of the EC9706/DDP cells was detected by MTT assay;the expression levels of PRR11 mRNA and protein in the EC9706/DDP cells and their parent EC9706 cells were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The EC9706/DDP cells were divided into control group,sh-NC group(infected with sh-NC),sh-PRR11 group(infected with sh-PRR11),sh-NC+DDP group(infected with sh-NC and treated with 4 mg·L-1 DDP),and sh-PRR11+DDP group(infected with sh-PRR11 and treated with 4 mg·L-1 DDP).The expression levels of PRR11 mRNA in the cells in various groups were detected by RT-qPCR method;the expression levels of PRR11,phosphoinositide 3-kinase(PI3K)p110α,protein kinase B(AKT),phosphorylated AKT(p-AKT),P-glycoprotein(P-gp),and multidrug resistance-associated protein 1(MRP1)proteins in the cells in various groups were detected by Western blotting method;the apoptotic rates of the cells in various groups were detected by flow cytometry.Results:The DDP-resistant cell line EC9706/DDP was successfully obtained,and the drug resistance index was 7.23±0.86.Compared with the EC9706 cells,the expression levels of PRR11 mRNA and protein in the EC9706/DDP cells were increased(P<0.05).Compared with control and sh-NC groups,the expression levels of PRR11 mRNA and protein in the cells in sh-PRR11 group were decreased(P<0.05),and the 50%inhibitory concentration(IC50)of DDP was decreased(P<0.05).Compared with sh-NC group,the expression levels of PI3K p110α,p-AKT,P-gp,and MRP1 proteins in the cells in sh-NC+DDP and sh-PRR11 groups were decreased(P<0.05),and the apoptotic rate of the cells was increased(P<0.05).Compared with sh-NC+DDP group and sh-PRR11 group,the expression levels of PI3K p110α,p-AKT,P-gp,and MRP1 proteins in the cells in sh-PRR11+ DDP group were increased(P<0.05),and the apoptotic rate of the cells was increased(P<0.05).Conclusion:Downregulating the expression of PRR11 gene in the drug resistant EC9706/DDP cells can inhibit the expressions of drug resistance-related proteins,reverse the resistance to DDP,and induce the apoptosis;its mechanism may be related to the inhibition of activation of the PI3K/AKT signaling pathway.
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Analgesia is an important link in the treatment of severe patients after neurosurgery and plays a vital role in improving the prognosis of the patients.Understanding the status quo and influencing fac-tors of pain in severe patients after neurosurgery helps to predict the occurrence of pain,which is crucial for determining the new pain assessment methods and auxiliary analgesic methods and developing novel analgesic drugs.This paper reviews the pain status,pain evaluation and analgesic methods of severe patients after neuro-surgery in recent years so as to understand the pain management current status of the patients with severe neurological conditions and provide reference for the medical staff to implement the analgesic programs.
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The goal of gastrointestinal endoscopy anesthesia management is to effectively calm and re-lieve pain while minimizing related adverse reactions and ensuring patient safety.Hypoxemia is the most com-mon adverse event during painless gastrointestinalendoscopy,and severe hypoxemia can cause cardiac and brain accidents.Therefore,how to prevent and reduce the occurrence of hypoxemia isa hot topic in clinical re-search.This article reviews the methods of preventing and reducing hypoxemia in general painless gastrointes-tinal endoscopy,and provides a reference for the selection of appropriate sedation and ventilation strategies for general painless gastrointestinal endoscopy anesthesia.
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Objective To investigate the need for and utilization of health services among six Zhiguo ethnic minority groups in Yunnan Province,aiming to provide further evidence for the improvement of healthcare.Methods Using stratified random sampling,1921 individuals from six Zhiguo ethnic minority groups,aged 15 and above,were investigated with a structured questionnaire between August and December 2022.A structured questionnaire was used to collect participants'information on health service needs and utilization.Results Am-ong the surveyed participants,the two-week prevalence rate was found to be 22.54%,while the prevalence rate of chronic diseases was 38.52%.Among the residents,the risk of two-week prevalence was higher for females(OR=1.564),individuals aged≥60 years(OR=1.727),and those who reported poorer health utility value(OR=5.277),while it was lower for residents of Keno(OR=0.470)and Lahu(OR=0.659)ethnicity,as well as those who reported higher EQ-VAS scores(OR=0.446/0.174).Meanwhile,residents aged≥45 years(OR=3.392/7.072)were at higher risk for chronic disease prevalence,while it was lower for Keno ethnicity(OR=0.409),unmarried individuals(OR=0.479),and those with higher education levels(OR=0.629/0.603),higher EQ-VAS scores(OR=0.208)P<0.05.Additionally,among the participants,the treat-ment rate for two-week illness was 14.32%,while the non-treatment rate stood at 36.49%.Furthermore,the one-year hospitalization rate was reported as 19.89%,with a corresponding rate of individuals who needed hospitalization but did not receive it being recorded at 15.86%.Among the residents,the likelihood of treatment for two-week illness was higher for females(OR=1.461)and residents aged≥45 years(OR=1.510/1.560),whereas it was lower for individuals with higher EQ-VAS scores(OR=0.445).The likelihood of hospitalization within one year was also higher for residents aged≥60 years(OR=2.029)and individuals of Nu(OR=1.599),Lisu(OR=1.688),and Keno(OR=1.968)ethnicity,whereas those with high EQ-VAS scores(OR=0.325)had a lower risk(P<0.05).Conclusion In Yunnan Province,the need for healthcare services among six Zhiguo ethnic minority groups in this study is relatively low;however,the high prevalence of chronic diseases raises concerns.The utilization of healthcare services appears to be relatively sufficient,but the utilization of outpatient services still needs to be improved.
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Objective To analyze the clinical characteristics of 310 patients with anti-tuberculosis drug-induced liver injury(ATB-DILI),to explore prognostic influencing factors,and to provide reference for its prevention and treatment.Methods Primary tuberculosis patients hospitalized in the Department of Tuberculosis of the Third People's Hospital of Kunming from November 2020 to November 2022 who met the diagnosis of ATB-DILI were enrolled.Statistics by gender,age,history,type of tuberculosis,co-morbidities,frequency of anti-tuberculosis regimens leading to liver injury,use of hepatoprotective drugs,and management and regression were performed to analyze the clinical characteristics of the patients and the factors influencing their prognosis.Results 310 patients were included,male,148(47.74%)and female,162(52.26%).The mean age was 44.33±17.47 years.Thirty-four patients had a history of allergy.The combination of isoniazid,rifampicin,pyrazinamide,and ethambutol(244 patients,78.71%)was the anti-tuberculosis regimen that resulted in the highest number of cases of hepatic injury.The median time between initiation of the tuberculosis regimen and the development of hepatic injury in patients with ATB-DILI was 30 d,and the mean duration of hospitalization was 16.39±7.01 d.The most used hepatoprotective drug was reduced glutathione(154 patients,49.68%),and most patients used a combination of 2 hepatoprotective drugs(128 patients,41.29%).Liver injury improved in 257 cases(82.90%)and failed in 53 cases(17.10%).The differences in alcohol consumption,severity,clinical staging,TT,ALP,TBIL,DBIL,IBIL,and GGT were statistically significant compared to those who did not recover(P<0.05),and severity and high ALP were independent risk factors for poor prognosis.Conclusions Patients should be carefully asked if they have a history of basic liver disease and alcoholism before using anti-tuberculosis drugs.In the course of anti-tuberculosis treatment,the combined use of anti-tuberculosis drugs is more serious than the use of single drugs to cause liver damage.Drugs that may cause liver damage should be used with caution and improved anti-tuberculosis programs should be explored.At the same time,liver function should be monitored regularly during anti-tuberculosis treatment,especially 30 days after medication,in order to reduce the occurrence of adverse reactions.
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BACKGROUND:Current rehabilitation programs are effective in treating post-stroke sequelae,but the treatment cycle is long and the labor cost is high.Brain-computer interface technology can be used for the treatment of post-stroke patients by extracting signals from the brain's neural activity through special equipment and converting this signal into commands that can be recognized by a computer. OBJECTIVE:To analyze and summarize the application of brain-computer interface technology in the upper limb motor function rehabilitation of stroke patients in recent years and to explore the clinical value of brain-computer interface technology in the upper limb function rehabilitation of stroke patients. METHODS:CNKI and PubMed were retrieved for relevant literature published from 2000 to 2022.The keywords were"stroke,electroencephalogram,brain-computer interface,upper limb,virtual reality technology,functional electrical stimulation,exoskeleton"in Chinese and"stroke,brain-computer interface,computer assistance,upper limb,virtual reality technology,functional electrical stimulation,exoskeleton"in English. RESULTS AND CONCLUSION:The brain-computer interface has shown promise for the restoration of upper limb motor function in stroke patients and has been shown to produce results that are unattainable with conventional treatments,and is well worth further research and promotion,but the mechanisms have not been fully elucidated.Also the ability to accurately decode all degrees of freedom of upper limb movements to provide flexible and natural control remains a challenge from the perspective of brain-computer interface systems that capture electroencephalogram signals from patients.Future research should focus on clarifying the specific neural mechanisms by which brain-computer interface technology facilitates upper limb motor recovery after stroke and identifying rehabilitation options such as brain-computer interfaces combined with external devices to facilitate upper limb motor function recovery in stroke patients.
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BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.
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Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.
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Objective To observe the changes of quadriceps tendon in type 2 diabetes mellitus(T2DM)patients based on ultrasonic elastography.Methods Data of 80 T2DM patients(T2DM group)and 80 healthy subjects(control group)were retrospectively analyzed.The general information and ultrasound elastography parameters,including strain ratio(SR)of the ratio of the proximal,middle and distal segments of quadriceps tendon and ipsilateral anterior femoral fat pad were compared between groups,while the correlations of the above SR with the disease course of T2DM and glycosylated hemoglobin(HbA1c)were explored.Results Fasting blood glucose and HbA1c in T2DM group were both significantly higher than those in control group(both P＜0.05).Compared with control group,SR of the proximal,middle and distal segments of quadriceps tendon in T2DM group were all significantly higher(all P＜0.05),especially the distal and proximal segments(t=6.01,5.92).In T2DM group,SR of the proximal,middle and distal segments of quadriceps tendon were positively correlated with the disease course of T2DM(r=0.45,0.20,0.43,all P＜0.05)and HbA1c(r=0.44,0.40,0.33,all P＜0.05).Conclusion SR of quadriceps tendon in T2DM patients significantly increased and positively correlated with the course of disease and HbA1c.
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Objective:To explore the changes of oxidative stress(OS),DNA damage and the occurrence of cellular premature aging of human immortalized keratinocytes(HaCaT)after that was radiated by X-ray with different doses.Methods:HaCaT cells were radiated by X-ray,and they were divided into 0 Gy group,5 Gy group and 10 Gy group according to the irradiation dose.The levels of intracellular reactive oxygen species(ROS)were detected by 2,7-Dichlorofluorescein diacetate(DCFH-DA)fluorescent probe,and the intracellular content of malondialdehyde(MDA)of lipid peroxidation products and the activity of superoxide dismutase(SOD)were measured by colorimetry.Immunofluorescence staining was used to detect the phosphorylated histone 2A variant(γ-H2AX)in HaCaT cells that were radiated by X-ray with different doses.Cell count kit-8(CCK-8)was used to detect the effect of X-ray with different doses on the proliferation of HaCaT cells after X-ray with different doses radiated them.β-Galactosidase staining was used to detect the proportion of premature aging cells.The changes of p21 and p53 protein expressions after X-ray irradiation were detected by Western blot.Results:After HaCaT cells were radiated by X-ray for 24h,the fluorescence intensity of 2',7'-Dichlorofluorescein(DCF)in 5 Gy and 10 Gy groups were significantly higher than that in the 0 Gy group,and the MDA contents of them were significantly higher than that in the control group,and the SOD activities of them were significantly lower than that in the control group(F=38.35,92.22,5.22,P<0.05),respectively.The change of γ-H2AX focus showed a dose-dependent significant increase at 1 h after irradiation,and the difference between them and control group was statistically significant(F=129.3,P<0.05).At 6h,24h and 48h after X-ray radiated HaCaT cells,the cell proliferation abilities of 5 Gy group and 10 Gy group were significantly decreased than that of 0 Gy group(F=116.41,62.20,34.29,P<0.01),and the β-Galactosidase activity of the two groups were significantly increased than that of 0 Gy group,and the difference was significant(F=1629.22,P<0.01).At 72h after X-ray with different doses radiated HaCaT cells,the expression levels of p21 and p53 proteins of 5 Gy group and 10 Gy group increased,and the differences of them among three groups were significant(F=104.4,66.69,P<0.01),respectively.Conclusion:Ionizing radiation can induce the occurrences of oxidative stress and DNA damage in HaCaT cells,and cause the occurrence of cellular premature aging.
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Objective:To explore the feasibility of chemical exchange saturation transfer (CEST) imaging at 3.0 T MRI in quantifying renal redox metabolism in vitro models and experimental animals.Methods:Redox metabolites in vitro models with physiological concentrations were prepared, including reduced metabolites (glutamate, alanine, glutathione) and oxidized metabolites (2-ketoglutarate, pyruvate, glutathione disulfide, ammonium hydroxide). CEST examinations were performed at 3.0 T MRI. The imaging parameters were as follows: CEST images with different saturation pulse intensity (B 1) (1, 2, 3, 4 μT) and a fixed radio frequency (RF) duration of 2 000 ms; CEST images with different RF durations (1 500 and 2 000 ms) were acquired with a fixed B 1 value of 2 μT to obtain the optimal scanning parameters. CEST examinations with optimized parameters were performed on the left kidneys of seven healthy rabbits, and the differences in magnetic resonance ratio asymmetry (MTR asym) between rabbit renal cortex and outer medulla were measured. A paired t-test was used to compare the differences. Results:The optimal B 1 for CEST examination of redox metabolites was 2 μT, and the optimal RF duration was 2 000 ms. The MTR asym peaks of glutathione disulfide, glutathione, glutamic acid, and alanine were at 3.75, 3.5, 3, and 1.5 ppm, respectively. The MTR asym peaks of pyruvate, 2-ketoglutarate, and ammonium hydroxide were at 1 ppm. The MTR asym peak values of reduced metabolites were higher than those of oxidized metabolites. When the B 1 value was 2 μT and the RF duration was 2 000 ms, the MTR asym signal of the renal cortex was (2.60±1.10) %, (2.86±1.32) %, (3.04±1.06) %, and (2.98±0.91) % at 1, 3, 3.5, and 3.75 ppm, respectively. The MTR asym signal of the outer medulla was (1.00±0.56) %, (2.43±0.94) %, (2.29±0.88) % and (1.98±0.58) %, respectively. The MTR asym signal of the renal cortex was higher than that of the outer medulla, and the differences were statistically significant ( t=3.04, P=0.023; t=2.56, P=0.043; t=3.50, P=0.013; t=3.45, P=0.014). Conclusion:CEST imaging at 3.0 T MRI can be used to quantitatively evaluate redox metabolism of healthy rabbit kidneys in vitro model and normal experimental rabbits.
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Objective:To construct a three-dimensional time-dose-response model for dose estimation and validate its feasibility.Methods:Based on a random number table, mice were divided into 0, 2, 4, 6, and 8 Gy groups for whole-body X-ray irradiation, with each group consisting of three mice. Hair follicle cells of whiskers were sampled at 1, 6, and 24 h after the irradiation. After immunofluorescence staining, the numbers of γ-H2AX foci at different time points from 1 to 24 h post-irradiation were observed using a confocal laser scanning microscope. The average numbers of γ-H2AX foci observed were corrected using the Dolphin’s model, followed by the fitting of dose-response curves. Using the R software, the equations and surfaces of the three-dimensional model for partial-body irradiation were established using the irradiation doses, post-irradiation time, and the corrected average numbers of γ-H2AX foci.Results:The average number of γ-H2AX foci increased with dose at fixed time points 1, 6, and 24 h but decreased with irradiation time at fixed doses 2, 4, 6, and 8 Gy. The dose-response curve equations of partial-body irradiation were fitted as follows: YF = 2.853+ 3.775 D, R2= 0.928, at 1 h after the irradiation; YF = 0.144+ 2.775 D, R2= 0.903, at 6 h after the irradiation; YF = 0.066+ 2.472 D, R2= 0.85, at 24 h after the irradiation. The three-dimensional model equation fitted was YF = 6.837 t-1.728+ 3.113 t-0.071D, R2=0.897. Substituting different post-irradiation time points into the three-dimensional surface model appeared as a two-dimensional linear model. By substituting the number of γ-H2AX foci and irradiation time into the linear and the three-dimensional models, both models yielded relative deviations between the estimated and actual radiation doses of 30% or less. Conclusions:The three-dimensional time-dose-response model, established by using the number of γ-H2AX foci to estimate partial-body irradiation doses, can be preliminarily applied for dose estimation at all time points 1-24 h after irradiation.
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Radiation-induced damage to vascular endothelium is a major complication of radiotherapy and a primary cause of morbidity and mortality in the population exposed to radiation. Ionizing radiation-induced cellular senescence serves as a critical factor in damage to vascular endothelial cells. Therefore, understanding the mechanisms of cellular senescence caused by senescence-associated secretory phenotype (SASP), as well as its role in ionizing radiation-induced damage to vascular endothelial cells, is significant for preventing and treating ionizing radiation-induced damage to vascular endothelial cells. In this study, the relationship between SASP-related premature senescence and this ionizing radiation-induced damage was explored from the following aspects: the mechanisms behind ionizing radiation-induced damage to vascular endothelial cells, ionizing radiation-induced cellular senescence, and the role of SASP-related premature senescence in the ionizing radiation-induced damage to vascular endothelial cells, as well as potential targets.
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Objective:To observe any effect of warm acupuncture on chondrocyte apoptosis and the miR-27a-mediated PI3K/AKT/mTOR signaling pathway using a rat model of early knee osteoarthritis (KOA).Methods:Fifty Sprague-Dawley rats were randomly divided into a control group, a model group, a warm acupuncture group, an inhibitor group, and an inhibitor + warm acupuncture group (the combined group), each of 10. Three days before the modeling, both the inhibitor and combined groups were injected with miR-27a inhibitor. Papain was then injected in all groups except the control group to establish the early KOA model. After successful modeling, the combined and warm acupuncture groups were given 30 minutes of warm acupuncture at the medial and lateral Xiyan points daily for 14 days. The model and inhibitor groups were fixed for 30 minutes during those sessions. After the 2 weeks, hematoxylin-eosin staining was used to observe any pathological changes in the cartilage tissue. Terminal deoxynucleoitidyl transferase-mediated nick end labeling was used to detect chondrocyte apoptosis, and enzyme-linked immunosorbent assays were employed to observe the levels of interleukin 1β (IL-1β) and IL-6. Western blotting was used to evaluate the expression of p-PI3K, p-AKT, p-mTOR, PI3K, AKT, mTOR, LC3-II, and Beclin1 proteins in the cartilage tissue, while quantitative real-time polymerase chain reactions detected the content of miR-27a.Results:After the intervention, the morphology of the chondrocytes in the warm acupuncture group had improved significantly compared to the model group, while that of the inhibitor and combined groups was better than among the warm acupuncture group. The rate of chondrocyte apoptosis in the warm acupuncture group was significantly lower than in the model group, while the rates of the inhibitor and combined groups were lower still. There was no significant difference between the inhibitor and the combination group on average. The average expression of IL-6, IL-1β, LC3-II and Beclin1 protein and of miR-27a were significantly lower in the warm acupuncture, inhibitor and combined groups than among the model group, with those of the inhibitor and combined groups significantly lower than among the warm acupuncture group, on average. The average p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR levels of the warm acupuncture, inhibitor and combined groups were significantly higher than those of the model group, with those of the inhibitor and combined groups significantly higher, on average, than among the warm acupuncture group. However, there was no significant difference between the inhibitor group and the combined group in their protein expression and mRNA levels.Conclusions:Warm acupuncture may down-regulate the expression of miR-27a to promote the activation of the PI3K/AKT/mTOR signaling pathway, inhibiting excessive autophagy and apoptosis. That would relieve inflammation and damage, and delay degeneration in early KOA, at least in rats.
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Syndrome differentiation and treatment is a traditional Chinese medicine （TCM）-featured concept and method in diagnosis and treatment， which needs to be combined with the intelligent diagnosis of TCM in the future. At present， the intelligent diagnosis of TCM has gradually changed from the simple data-driven primary intelligence to the knowledge-driven advanced intelligence that integrates professional knowledge. Although syndrome element differentiation breaks down the elements of TCM diagnostic knowledge to form syndrome elements， which makes the original vague knowledge information more specific， the relationship between syndrome elements is not well classified and sorted out， resulting in the lack of hierarchical relationship and connection between syndrome elements， and thereby causing obstacles to the application of intelligent technology. Based on the understanding of etiology and pathogenesis from TCM， this paper concretized the syndrome element set of etiology， disease location and disease nature in TCM syndrome differentiation and treatment， and formed a knowledge framework system of syndrome elements with clear logical relationship， clear hierarchy and good explanation， thereby providing certain reference for realizing knowledge-driven advanced intelligence syndrome differentiation in the future.
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Developmental dyslexia (DD) is a prevalent learning disorder, and the KIAA0319 gene is a DD-associated gene, potentially affecting reading ability by influencing brain development. This review provides an overview of the impact of KIAA0319 gene on brain development in fish, non-primate mammals, primate mammals, and humans. In studies involving fish, the kiaa0319 gene was found to be expressed in the brain, eyes and ears of zebrafish. In mammalian studies, abnormal Kiaa0319 gene expression affected neuronal migration direction and final position, as well as dendritic morphology during embryonic development in rats, leading to abnormal white and gray matter development. Knocking down the Kiaa0319 gene impaired the primary auditory cortex in rats, resulting in phoneme processing impairment similar to DD. In mice, Kiaa0319 overexpression affected the neuronal migration process, causing delayed radial migration of neurons to the cortical plate. Knockout of the Kiaa0319 gene led to abnormal development of the gray matter in mice, resulting in reduced volume of the medial geniculate nucleus and then impacting auditory processing. In primate studies, research on marmosets found that KIAA0319 gene is expressed in the visual, auditory, and motor pathways, while studies on chimpanzees revealed that KIAA0319 gene abnormalities primarily affected the gray matter volume and microstructure of the posterior superior temporal gyrus, morphology of the superior temporal sulcus and gray matter volume of the inferior frontal gyrus. The impact of KIAA0319 gene on human brain development is mainly concentrated in the left temporal lobe, where abnormal KIAA0319 gene expression caused reduced gray matter in the left inferior temporal gyrus, middle temporal gyrus and fusiform gyrus, as well as reduced white matter volume in the left temporoparietal cortex. Abnormalities in KIAA0319 gene also led to decreased hemispheric asymmetry in the superior temporal sulcus. The above-mentioned brain regions are crucial for language and reading processing. It is analyzed that the abnormalities in the DD-associated KIAA0319 gene affect neuronal migration and morphology during brain development, resulting in abnormal development of subcortical structures (such as the medial geniculate nucleus and lateral geniculate nucleus) and cortical structures (including the left temporal cortex, temporoparietal cortex and fusiform gyrus) which are involved in human visual and auditory processing as well as language processing. Impairment of the medial geniculate nucleus affects the information transmission to the auditory cortex, leading to impaired phoneme processing. Abnormalities in the magnocellular layers within the lateral geniculate nucleus hinder the normal transmission of visual information to the visual cortex, affecting the dorsal visual pathway. The left temporal lobe is closely related to language and reading, and abnormalities in its gray matter and connections with other brain areas can affect the language and word processing. In summary, abnormalities in the KIAA0319 gene can partly explain current research findings on the cognitive and neural mechanisms of DD, providing a genetic basis for theoretical models related to DD (such as general sensorimotor theory and the magnocellular theory). However, the mechanism of developmental dyslexia is complex, and there are mutual influences between different DD-associated genes and between genes and the environment, which require further exploration.
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N6-methyladenosine(m6A), the most common, abundant, and conserved RNA modification in eukaryotic cells, regulates RNA splicing, stability, output, degradation and translation through m6A methyltransferase, m6A demethylase, and m6A methylated binding proteins. Recent studies have found that abnormal m6A methylation may mediate a variety of pathological processes in eyes and participate in the occurrence and development of metabolic, inflammatory, degenerative ocular diseases and ocular tumors, such as diabetic retinopathy, cataract, age-related macular degeneration and uveal melanoma. This review aims to summarize the roles of m6A methylation modification in ocular cells and ocular diseases, elucidate the potential molecular mechanisms of m6A methylation in ocular diseases, so as to encourage innovative approaches in the treatment of these ocular diseases.
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ObjectiveTo explore the effect of brain-computer interface (BCI) based on visual, auditory and motor feedback combined with transcranial direct current stimulation (tDCS) on upper limb function in stroke patients. MethodsFrom March to October, 2023, 45 stroke inpatients in Xuzhou Rehabilitation Hospital and Xuzhou Central Hospital were divided into BCI group (n = 15), tDCS group (n = 15) and combined group (n = 15) randomly. All the groups received routine rehabilitation, while BCI group received BCI training, tDCS group received tDCS, while the combined group received tDCS and followed by BCI training immediately, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT), modified Barthel Index (MBI) and delta-alpha ratio (DAR) and power ratio index (PRI) of electroencephalogram before and after treatment. ResultsThe scores of FMA-UE, ARAT and MBI increased in all the groups after treatment (|t| > 5.350, P < 0.001), and all these indexes were the best in the combined group (F > 3.366, P < 0.05); while DAR and PRI decreased in all the groups (|t| > 2.208 , P < 0.05), they were the best in the combined group (F > 5.224, P < 0.01). ConclusionBCI based on visual, auditory and motor feedback combined with tDCS can further improve the motor function of upper limbs and the activities of daily living of stroke patients.