Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

Objective To acquire the external contour changes and positioning errors during fractionated intensity-modulated radiotherapy for nasopharyngeal carcinoma using kilovoltage cone-beam computed tomography(CBCT),and to analyze their effects on the dose distributions in target areas and organs-at-risk.Methods Twenty-one patients with nasopharyngeal carcinoma were enrolled in the study,and the positioning errors in the left-right,superior-inferior and anterior-posterior directions were obtained by matching 137 CBCT images with the positioning CT images.The transverse width of the external contour was measured at 3 different layers of the neck,and its effects on positioning errors were analyzed using Pearson's coefficient and independent sample t-tests.Additionally,simulation plans based on CBCT images were created to analyze the effects of positioning errors and external contour changes on radiotherapy dose,with Mann-Whitney U tests applied for significance analysis.Results The positioning errors in the left-right,superior-inferior and anterior-posterior directions were(1.04±0.73),(1.13±0.87)and(1.38±0.95)mm,respectively.The rates of external contour changes at the A,B and C layers of the head and neck were 15.36%,14.94%and 14.99%,respectively.Compared with executed plans,simulation plans had lower GTV D98,CTV1 D95 and CTV2 D95(P<0.05),and higher Dmax for the brainstem and spinal cord(P<0.05).Conclusion The simulation plans indicate that the presence of uncertainties such as positioning errors and external contour changes will significantly affect dose distributions in target areas,with the largest decrease observed in GTV D98(11.49%)and the maximum change rates in CTV1 D95 and CTV2 D95 being 12.88%and 21.64%,respectively.Except for the left and right lenses and left parotid gland,significant differences are observed in the doses for the other organs-at-risk and target areas,suggesting that positioning errors and external contour changes in actual radiotherapy will exert significant effects on dose distributions.

Objective:To explore the feasibility of constructing automatic intensity-modulated radiotherapy (IMRT) plans for cervical cancer based on Pinnacle scripts and to assess the advantages of this method in designing treatment plans for cervical cancer.Methods:A retrospective analysis was conducted for 40 cases of cervical cancer treated with IMRT in the department of radiation oncology of the First Affiliated Hospital of Bengbu Medical University. Among them, the data of 25 cases were employed as a reference for the initialization of objective functions. The scripts for automatic plans were designed in the Pinnacle planning system. For the remaining 15 cases, automatic and manual IMRT plans were designed (also referred to as the automatic planning group and the manual planning group, respectively). The design times of both groups were compared. Furthermore, both the dosimetric parameters of target volumes and the irradiation doses to organs at risk (OARs) were also compared between the two groups using dose-volume histograms.Results:Compared to the manual planning group, the automatic planning group exhibited a statistically significant decrease in the average design time of 32.81 min ( t = -12.91, P < 0.05), a statistically significant increase in the conformity index of the target areas of 0.01 ( t = -0.08, P < 0.05), and a decrease in the uniformity index of the target areas of 0.02. Compared to those of the manual planning group, the bladder′s V40 and V45 and the rectum′s V40 and V45 of the automatic planning group decreased by 6.88%, 4.12%, 9.93%, and 12% on average, respectively ( t = -4.49, -4.46, -3.62, -5.80, P < 0.05). Minimal differences were observed in the V30, V50, and Dmax of the small intestine between both groups, without statistically significant differences in V30 and Dmax ( P > 0.05). Compared to the manual planning group, the automatic planning group displayed decreases in the V45 and Dmeanof the bilateral femoral head of 7.9% and 106.83 cGy, respectively and a decrease in the spinal Dmax of 100.14 cGy, with statistically significant differences ( t = -6.00, -2.52, -2.55, P < 0.05). Conclusions:Automatic IMRT plans for cervical cancer, constructed based on Pinnacle scripts, can significantly reduce irradiation doses to OARs and enhance the efficiency of the plan design while ensuring dose uniformity and conformality of target areas.

Aiming at the problems of missing important features, inconspicuous details and unclear textures in the fusion of multimodal medical images, this paper proposes a method of computed tomography (CT) image and magnetic resonance imaging (MRI) image fusion using generative adversarial network (GAN) and convolutional neural network (CNN) under image enhancement. The generator aimed at high-frequency feature images and used double discriminators to target the fusion images after inverse transform; Then high-frequency feature images were fused by trained GAN model, and low-frequency feature images were fused by CNN pre-training model based on transfer learning. Experimental results showed that, compared with the current advanced fusion algorithm, the proposed method had more abundant texture details and clearer contour edge information in subjective representation. In the evaluation of objective indicators, Q ^AB/F, information entropy (IE), spatial frequency (SF), structural similarity (SSIM), mutual information (MI) and visual information fidelity for fusion (VIFF) were 2.0%, 6.3%, 7.0%, 5.5%, 9.0% and 3.3% higher than the best test results, respectively. The fused image can be effectively applied to medical diagnosis to further improve the diagnostic efficiency.
Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging/methods* ; Algorithms

Objective:To construct a predictive nomogram incorporating pretreatment CT-based radiomics for radiation pneumonitis (RP) in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT), and to evaluate the value of CT radiomics in predicting RP.Methods:Clinical data of 267 EC patients sequentially treated with IMRT in Quanzhou First Hospital affiliated to Fujian Medical University from January 2019 to December 2021 were prospectively analyzed. Among them, the first 206 patients were assigned into the training cohort and the last 61 patients were enrolled in the validation cohort. Radiomics features of bilateral lungs were extracted by radiotherapy CT simulation. Univariate analysis was performed to screen the potential predictive variables for symptomatic RP. Machine learning algorithms, such as least absolute shrinkage and selection operator (LASSO), extreme gradient boosting (XGboost), and support vector machine (SVM), were performed for radiomic features selection, respectively. The best classifier was chosen to construct a radiomic signature (RS). Clinical, radiomics and combined nomogram predictive model were developed, respectively. The predictive efficiency and clinical benefits of three models were compared by calculating the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and decision curve analysis (DCA), and then validated in the validation cohort. Multivariate logistic regression analysis was conducted. Different ROC curves were compared by Delong test.Results:Cardiovascular disease, minimum internal diameter of esophagus and adjuvant chemotherapy and RS were the independent related factors of RP. The AUC of clinical, radiomics and combined models were 0.772, 0.745, 0.842 in the training cohort, and 0.851, 0.811, 0.901 in the validation cohort, respectively. DCA showed that combined radiomic model yielded better clinical benefits compared with clinical model.Conclusion:Radiomics features from pretreatment CT have the potential of improving the efficiency of RP prediction models for EC patients treated with IMRT.

BACKGROUND: Hypertensive heart disease (HHD) poses a public health challenge, but data on its burden and trends among older adults are scarce. This study aimed to identify trends in the burden of HHD among older adults between 1990 and 2019 at the global, regional, and national levels. METHODS: Using the Global Burden of Diseases study 2019 data, we assessed HHD prevalence, death, and disability-adjusted life-year (DALY) rates for individuals aged 60-89 years at the global, regional, and national levels and estimated their average annual percentage changes (AAPCs) between 1990 and 2019 using joinpoint regression analysis. RESULTS: In 2019, there were 14.35 million HHD prevalent cases, 0.85 million deaths, and 14.56 million DALYs in older adults. Between 1990 and 2019, the prevalence of HHD increased globally {AAPC, 0.38 (95% confidence interval [CI], 0.36, 0.41)} with decreases observed in mortality (AAPC, -0.83 [95% CI, -0.99, -0.66]) and the DALY rate (AAPC, -1.03 [95% CI, -1.19, -0.87]). This overall global trend pattern was essentially maintained for sex, age group, and sociodemographic index (SDI) quintile except for non-significant changes in the prevalence of HHD in those aged 70-74 years and in the middle SDI quintile. Notably, males had a higher HHD prevalence rate. However, HHD-related mortality and the DALY rate were higher in females. The middle SDI quintile experienced the largest decreases in mortality and the DALY rate, with a non-significant decline in prevalence between 1990 and 2019. There were significant discrepancies in the HHD burden and its trends across regions and countries. CONCLUSIONS In the past three decades, there has been an overall increasing trend in the prevalence of HHD among older adults worldwide despite decreasing trends in mortality and the DALY rate. Better management of hypertension, and prevention and control of HHD are needed in older adults.
Male ; Female ; Humans ; Aged ; Quality-Adjusted Life Years ; Global Burden of Disease ; Prevalence ; Hypertension/epidemiology* ; Heart Diseases ; Incidence

Objective: To investigate the characteristics of intestinal microflora among flying personnel with hyperlipidemia, so as to provide insights into prevention of hyperlipidemia among flying personnel. Methods : Flying personnel diagnosed with hyperlipidemia in a sanatiorium from October 2020 to February 2021 were included in the hyperlipidemia group, while flying personnel with normal blood lipids during the same period served as controls. Subjects' age, family history, physical examinations and blood testing results were collected from both groups. Fecal samples were collected, and intestinal microflora was sequenced followed by bioinformatics analysis. The diversity and abundance of intestinal microflora were compared, and the key bacteria were screened using LEfSe analysis. Results: There were 29 subjects in the hyperlipidemia group with a median age (interquartile range) of 34 (12) years and 25 subjects in the control group with a median age (interquartile range) of 30 (12) years, and all subjects were men. There were no significant differences between the two groups in terms of age, flight duration, smoking, family history of metabolic diseases and waist circumference (P>0.05). The Shannon diversity index of intestinal microflora was lower in the hyperlipidemia group than in the control group (Z=4.370, P=0.026), and there was a significant difference in the overall structure of intestinal flora between the two groups, which were clustered into two groups. LEfSe analysis identified Herbaspirillum, Atopobium and Eggerthella as key microorganisms in the hyperlipidemia group, and Agathobacter, Dialister, norank_Eubacterium_coprostanoligenes_group, Alloprevotella and unclassified Bacteroidales as key microorganisms in the control group. Conclusions The species diversity and relative abundance of intestinal microflora are lower in flying personnel with hyperlipidemia than in those with normal blood lipids. Herbaspirillum, Atopobium and Eggerthella may be the key bacteria contributing to hyperlipidemia among flying personnel.