ObjectiveTo investigate the mechanism of action and main active components of Xiaoyaosan in the treatment of diabetic mellitus-induced erectile dysfunction （DMED）. MethodStreptozotocin （STZ） was used to induce a diabetic rat model. The therapeutic efficacy of Xiaoyaosan was evaluated by measuring intracavernous pressure/mean arterial pressure （ICP/MAP） and using Masson's trichrome staining. The main active components， key targets， and potential signaling pathways of Xiaoyaosan for the treatment of DMED were predicted by network pharmacology and molecular docking. The predicted results were then validated by in vitro and in vivo experiments. ResultThe ICP/MAP measurements and Masson's staining results showed that compared with the results in the control group， the erectile function of rats in the model group was significantly reduced （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly reduced （P<0.01）. After treatment with Xiaoyaosan， compared with the results in the model group， the ICP/MAP value of the diabetic rats was significantly elevated （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly higher （P<0.01）. The results of network pharmacology showed that Xiaoyaosan acted on key targets such as albumin （ALB）， protein kinase B1 （Akt1）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF） through its main active components， including quercetin， kaempferol， β-sitosterol， and stigmasterol. These components were involved in the regulation of the advanced glycation end-products/receptor for advanced glycation end-products （AGE/RAGE） signaling pathway and the phosphoinositide 3-kinases（PI3K）/Akt signaling pathway in diabetic complications. The results of molecular docking showed that the key components of Xiaoyaosan had good binding capabilities with core targets， with β-sitosterol showing the strongest binding affinity with ALB. In vivo experiments demonstrated that Xiaoyaosan could significantly increase the protein and mRNA expression of ALB and Akt1 in serum， and inhibit the expression of IL-6 and TNF-α. It also significantly upregulated the expression of protein and mRNA of phosphorylation（p）-PI3K and p-Akt， and inhibited the RAGE expression. The results of cellular thermal shift assay （CETSA） showed that β-sitosterol could significantly inhibit the degradation of ALB protein. ConclusionXiaoyaosan may restore erectile function in diabetic rats by modulating targets such as ALB， Akt1， IL-6， and TNF， and through the RAGE/PI3K/Akt signaling pathway， and its main active component is likely β-sitosterol.

Objective:To explore the value of conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI) sequence and pathological examination in predicting the efficacy of neoadjuvant chemotherapy (NAC) in advanced breast cancer.Methods:The clinical data of 65 cases of advanced breast cancer with NAC confirmed by pathology in the Affiliated Hospital of Jining Medical University from March 2022 to May 2023 were retrospectively analyzed, including 20 cases in the pathological complete remission (pCR) group and 45 cases in the non pCR group; All patients underwent routine MRI, DWI, DKI examinations and pathological analysis. The clinical pathological data, routine MRI features, apparent diffusion coefficient (ADC) values, mean kurtosis coefficient (MK), and mean diffusion coefficient (MD) between the two groups were analyzed; We compared the differences in various parameters between two groups and plotted receiver operating characteristic (ROC) curves to compare their diagnostic efficacy of NAC in breast cancer.Results:There were significant differences in molecular typing, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and Ki-67 between pCR group and non pCR group (all P<0.05). In pCR group, Her-2 overexpression type and triple negative breast cancer (TNBC) type breast cancer were more common. ER and PR were mostly negative, Her-2 was mostly positive, and Ki 67 was mainly positive. The difference in tumor T2WI signal between the pCR group and the non pCR group was statistically significant ( P<0.05), with the pCR group showing mostly moderate/low T2WI signal. The ADC and MD values of the pCR group were lower than those of the non pCR group, while the MK value of the pCR group was higher than that of the non pCR group, and the differences were statistically significant (all P<0.001). The area under the ROC curve (AUC) for predicting the efficacy of NAC using a clinical pathological model was 0.829, which was higher than the AUC of molecular subtypes, ER, PR, Her-2, and Ki-67 ( Z=3.008, 2.697, 2.815, 2.131, 2.376, all P<0.05); The AUC of the DKI+ DWI predicting the efficacy of NAC was 0.934, which was higher than that of the DWI single sequence model, and the difference in type was statistically significant ( Z=2.396, P=0.017). The diagnostic efficacy of the DKI+ DWI model was higher than that of the single parameter ADC, MD, and MK, and the differences were statistically significant ( Z=2.396, 2.219, 2.161, all P<0.05); The AUC of the combined imaging and pathology model was 0.983, and its diagnostic efficacy was higher than that of the conventional MRI feature model, pathology model, DWI model, and DKI model, with statistically significant differences ( Z=5.877, 2.961, 3.240, 2.264, all P<0.05). Conclusions:The results of pathology, conventional MRI, DWI and DKI parameters of pCR and non pCR breast cancer patients are significantly different, and the combined model is better than the single model in predicting the efficacy of NAC.

ObjectiveTo investigate the effect of multimodal mirror therapy on upper limb and hand function in stroke patients. MethodsFrom April, 2021 to August, 2022, 60 stroke patients from the Department of Rehabilitation Medicine of Zhejiang Provincial People's Hospital were randomly divided into group A (n = 20), group B (n = 20) and group C (n = 20). All the patients accepted routine rehabilitation, while group B accepted mirror therapy, and group C accepted multimodal mirror therapy, in addition, for six weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Upper Extremity Function Test (UEFT) and modified Barthel Index (MBI), while the maximum grip strength and pinch strength of the affected hand were measured. ResultsThe FMA-UE score, UEFT score, maximum hand grip strength and pinch strength, and MBI scores improved in all groups after treatment (|t| > 7.878, P < 0.001), and it was the most in group C (F > 12.563, P < 0.001). ConclusionMultimodal mirror therapy may further improve the upper limb motor function and hand function of stroke patients, as well as the strength of the affected hand and the activities of daily living.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Objective:To study the common pharmacodynamic substance basis and potential mechanism of Dihuang Decoction in treating Alzheimer disease (AD) and diabetes mellitus (DM) with same method based on network pharmacology; To provide bioinformatics basis.Methods:The effective components of Dihuang Decoction were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and CNKI. The drug targets were obtained by combining and UniProt database. The targets of AD and DM related diseases were obtained by GeneCards, OMIM and TTD databases respectively. Cytoscape 3.7.1 software was used to construct the Disease - drug - component - target network. R studio software was used to construct a Circos diagram of the effective compounds and disease targets.Protein-protein interaction (PPI) network was constructed using STRING platform. GO enrichment and KEGG enrichment analysis was conducted through DAVID database, Metascape, R Studio software.Results:A total of 206 active components were obtained; PPI network construction screened 51 key targets; GO enrichment analysis revealed the functions of GABA, cholinergic synapse, estrogen response, BCL-2 family protein complex and so on; KEGG enrichment analysis revealed FoxO signaling pathway, HIF-1 signaling pathway, insulin resistance pathway and other pathways.Conclusion:Dihuang Decoction has the synergistic characteristics of multiple components, multiple targets and multiple pathways in treating AD and DM with same method, mainly through proanthocyanidin B7, proanthocyanidin B5, proanthocyanidin B1 and other active ingredients, acting on TNF, IL-6, ESR1, PPARG, AKT1 and other targets, regulating FoxO signaling pathway, HIF-1 signaling pathway, etc.

In recent years, with the continuous studies on tumor metabonomics, more and more results have shown that changes of metabolism play important roles in the occurrence and development of malignant tumor. Carcinogenic factors can destroy the metabolic balance of human body, induce metabolic reprogramming, and then mediate a variety of biological behaviors to partici-pate in the proliferation and invasion of cancer cells. Lipids provide the body with the necessary energy and essential fatty acids, and a variety of lipid molecules and metabolites are involved in cell signal transduction. Lipid metabolism is an important link in the metabolic system of the body, and the relationship between the occurrence and development of pancreatic cancer and lipid metabo-lism is not clear. The purpose of this paper is to reveal the changes of lipid metabolism in pancreatic cancer, summarize some preclinical studies and clinical trials, and deeply explain the research status of abnormal lipid metabolism associated with pancreatic cancer, so as to provide new ideas for the study of pancreatic cancer pathogenesis and accurate treatment.

Objective:To investigate the protective effect and mechanism of Icaritin Ⅱ (ICAⅡ) on bladder in radiation cystitis model.Methods:A total of 18 10-week-old male SD rats were selected from July 2021 to March 2022 and divided into control group, model group and treatment group by random number table method, with 6 cases in each group. Model group and treatment group were given a single dose of 20 Gy X-ray irradiation in the pelvic area. 24 h after irradiation, the treatment group was given ICAⅡ 4.5 mg/(kg·d) gavage, while the control group and model group were given the same volume of solvent (10% anhydrous ethanol, 20% isopropyl alcohol, 30% polyethylene glycol and 40% deionized water) gavage for 4 consecutive weeks. Drug eluting for 1 week. The bladder volume and leakage point pressure of the three groups of rats were measured by multi-conducting physiological apparatus, and the bladder function was evaluated. HE staining, Masson staining, ELISA, TUNEL staining and western blotting were performed on the bladder samples of the three groups of rats. The pathological changes (thickness of bladder mucosa, ratio of smooth muscle to collagen fiber), oxidative stress level (superoxide dismutase SOD, malondialdehyde), apoptosis rate, protein levels of inflammatory factors (IL-6, NF-kB) and anti-oxidative stress signaling pathway factors (Nrf2, HO-1) of the three groups of rats were compared.Results:After 4 weeks of modeling, in the model group, the bladder volume [(1.01±0.12)ml vs. (1.58±0.21)ml, P=0.001], the bladder leakage point pressure [(38.79±4.12) cmH 2O (1 cmH2O=0.098 kPa)vs.(60.59±3.81) cmH 2O, P=0.001], the ratio of smooth muscle of bladder wall to collagen fiber [1.78±0.17 vs.3.15±0.57, P=0.001], SOD[(6.31±0.73) U/mg vs.(14.67±1.04) U/mg, P=0.001] were lower than the control group, and the differences were statistically significant. In the model group, the thickness of bladder mucosa [(47.33±1.78)μm vs.(20.83±2.33)μm, =, P=0.001], malondialdehyde [(1.01±0.13) nmol/mg vs.(0.49±0.03) nmol/mg, P=0.001], IL-6 (0.87±0.11 vs. 0.33±0.10, P=0.001), NF-kB (0.71±0.14 vs. 0.29±0.07, P=0.001), apoptosis rate [(11.60±3.04)% vs. (3.91±1.40)%, P=0.007] was higher than the control group, and the differences were statistically significant. In the treatment group, the bladder volume [(1.27±0.13)ml, P=0.030], bladder leakage point pressure [(47.83±2.50)cmH 2O, P=0.004], smooth muscle to collagen fiber ratio (2.78±0.68, P=0.015), SOD[(10.48±0.85) U/mg, Compared with model group, bladder mucosa thickness [(31.94±3.20)μm, P=0.001], malondialdehyde [(0.64±0.09) nmol/mg, P=0.001], IL-6 (0.69±0.11, P=0.035), NF-kB (0.45±0.06, P=0.002) and apoptosis rate [(6.05±0.60)%, P=0.030] were lower than those in model group. The protein expression level of Nrf2 in model group (0.73±0.08 vs. 0.58±0.11, P=0.023) was higher than that in control group, but there was no significant difference in the protein expression level of downstream antioxidant factor HO-1 (0.50±0.14 vs. 0.35±0.06, P=0.060). Nrf2 protein expression level (0.88±0.03, P=0.027) and HO-1 expression level (0.68±0.07, P=0.026) in treatment group were higher than those in model group. Conclusion:ICAⅡ can reduce radiation cystitis injury, and its mechanism may be related to anti-oxidative stress and reducing inflammation.

Pancreatic cancer is a rapidly progressive and highly malignancy of the digestive system. In recent years, the diagnosis and treatment of pancreatic cancer has been in a slow stage of development, and the 5-year survival rate of patients remains very low. The main objective of translational medicine is to remove the barriers between basic medical research and clinical medical applications, to achieve practical integration between laboratory and clinic, and to accelerate the translation of the results obtained from basic research into clinical diagnosis, evaluation and treatment of diseases, thus promoting the development of life sciences. With the rapid development of the concept and technology of translational medicine, its application in the early diagnosis of pancreatic cancer can bring new hope for effectively improving the overall prognosis of patients. The authors comprehensively analyzed the latest research progress of translational medicine in the early diagnosis of pancreatic cancer in order to improve the early diagnosis and long-term survival of pancreatic cancer patient.

Objective:To compare the dosimetric difference between knowledge-based planning (KBP) volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) models for predicting the dose distribution during IMRT, aiming to investigate the feasibility of VMAT model to predict the IMRT plans.Methods:Fifty prostate cancer patients who had completed radiotherapy were selected. Manual planning was performed on each selected patient to generate the corresponding IMRT and VMAT plans. The IMRT and VMAT manual plans of the 40 randomly-selected patients were adopted to generate the KBP VMAT and IMRT models. The remaining 10 patients were utilized to predict IMRT plans. VMAT library-derived IMRT model (V-IMRT) and IMRT library-derived IMRT model (I-IMRT) were generated. Dosimetric parameters related to organ-at-risks (OARs) and planning target volume (PTV) were statistically compared among the manual IMRT (mIMRT), V-IMRT and I-IMRT plans.Results:Compared with the mIMRT plan, I-IMRT could significantly better control D max of the PTV ( P=0.039), whereas V-IMRT and I-IMRT plans could better protect the bladder and bilateral femoral heads (both P<0.05). V-IMRT plan could better protect the D max of bilateral femoral heads and the D 15% of the right femoral head (both P<0.05), whereas no significant difference was observed in other OARs and PTV (all P>0.05). Conclusions:Compared with the manual plans, KBP IMRT plan has significant advantages in protecting the OARs. KBP VMAT and IMRT models are both feasible in clinical practice, which yield equivalent accuracy for predicting IMRT plan.

Allografts ; COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Kidney Transplantation/adverse effects* ; SARS-CoV-2