OBJECTIVE To investigate the impact of dapagliflozin on contrast-induced acute kidney injury （CIAKI） and prognosis in patients with diabetes mellitus type 2 （T2DM） and acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS Retrospective selection of data on T2DM patients with ACS who underwent PCI treatment in the Cardiology Department of Tianjin Chest Hospital from January 1st 2021 to December 31st 2022. The patients were divided into dapagliflozin group （96 cases） and control group （148 cases） based on whether they received dapagliflozin or not. Renal function indicators were measured for all enrolled patients before PCI and at 48 h and 1 week after PCI， including blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， cystatin-C （Cys-C）， kidney injury molecule-1 （KIM-1） and β2-microglobulin （β2-MG）. All patients were followed up for at least 1 year. The incidence of CIAKI and major adverse cardiac event （MACE） during follow-up were recorded for both groups. Logistic regression was used to analyze the impact of dapagliflozin on the occurrence of CIAKI， while the Log-rank test was applied to compare the incidence of MACE between the two groups. Cox regression was employed to analyze the impact of dapagliflozin on prognosis. RESULTS At 48 h and 1 week after PCI， serum levels of Cys-C， KIM-1 and β2-MG were significantly lower in the dapagliflozin group compared to the control group （P＜0.05）. The incidence of CIAKI was lower in the dapagliflozin group compared to the control group （6.25% vs. 14.86%， P＝0.042）. Logistic regression analysis revealed that dapagliflozin was an independent protective factor against CIAKI （OR＝0.280， 95%CI 0.101-0.780，P＝0.015）. During the follow-up period， the incidence of MACE was lower in the dapagliflozin group compared to the control group （7.29% vs. 17.57%， P＝0.049）. Cox regression analysis indicated that dapagliflozin reduced the occurrence of MACE after PCI （HR＝0.374， 95%CI 0.161-0.866， P＝0.022）. CONCLUSIONS With adequate hydration， the use of dapagliflozin does not increase the risk of CIAKI following PCI in T2DM patients with ACS.

Objective To obtain the data of radiological diagnosis and treatment resource distribution at medical institutions of different levels and in various cities, understand the status of resource allocation, provide policy-making basis and suggestions for optimizing the allocation of radiological diagnosis and treatment resources within the province, and offer data and references for related research. Methods A basic situation questionnaire survey was conducted on radiological diagnosis and treatment institutions in Hunan Province. Data were reviewed, analyzed, and statistically processed using Excel software to understand the allocation situation of radiological diagnosis and treatment resources in Hunan Province. Results As of 2022, there were 3031 radiological diagnosis and treatment institutions, 19770 radiation workers, and 6617 pieces of radiological diagnostic and treatment equipment. There were 80 radiation treatment institutions, 49 nuclear medicine institutions, 178 interventional radiology institutions, and 3028 X-ray imaging diagnosis institutions. There were 1077 radiation workers in radiation treatment, 461 radiation workers in nuclear medicine, 3369 radiation workers in interventional radiology, and 14,863 radiation workers in X-ray imaging diagnosis. There were 135 pieces of radiation treatment equipment, 56 pieces of nuclear medicine equipment, 262 pieces of interventional radiology equipment, and 6164 pieces of X-ray imaging diagnosis equipment. Conclusion Primary and lower grade medical institutions in Hunan Province account for a relatively high proportion of the total number of medical institutions, whereas radiological diagnostic and treatment resources are predominantly concentrated in tertiary medical institutions, demonstrating a unbalanced allocation of radiological diagnosis and treatment resources in various cities. In terms of the overall allocation of radiological diagnosis and treatment resources, interventional radiology is superior to the national average, nuclear medicine and X-ray imaging diagnosis are comparable to the national averages, and radiation treatment is lower than the national average. The total GDP is not the decisive factor in determining the development of local medical levels. It is suggested that relevant authorities should improve the rationality of the planning for the allocation of radiological diagnosis and treatment resources, promote the allocation of radiological diagnosis and treatment resources to the grassroots and underdeveloped areas through various measures, and thus achieve the goal of balanced resource allocation.

Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.

Objective To explore the effect of Shuanglu Tongnao Formula on neuronal ferroptosis in ischemic stroke rats and its regulatory mechanism on the silent information regulator 2 homolog 1(SIRT1)/nuclear factor erythroid 2-related fac-tor 2(Nrf2)/glutathione peroxidase 4(GPx4)signaling pathways.Methods Twenty rats were selected as sham operation group by the random number table method,and the remaining seventy rats were made ischemic stroke rat models by the middle cerebral artery occlusion method.The rats that had been successfully modeled were randomly divided into the model control group,Shuanglu Tongnao formula group,Shuanglu Tongnao formula+SIRT1 inhibitor group(Shuanglu Tongnao formula+EX527 group),with 20 rats in each group.After 14 days,the rats were scored for neurological injury;TTC staining was applied to detect the area of cerebral infarction in rats;HE staining was applied to detect pathological changes in rat brain tissue;Nissl staining was applied to detect the number of neurons in rat brain tissue;the kit was applied to detect the levels of ferri ion(Fe2+),superoxide dismutase(SOD),glutathione(GSH),and malonaldehyde(MDA)in rat brain tissue;immunohistochemistry was applied to de-tect the positive expression of acyl-CoA synthetase long-chain family member 4(ACSL4),transferrin receptor(TFR),and ferritin heavy polypeptide 1(FTH1)proteins in rat brain tissue;Western blotting method was applied to detect the expression of SIRT1,Nrf2,GPx4,and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11)proteins in rat brain tissue.Results Compared with the sham operation group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expressions of ACSL4 and TFR in model control group were increased(P<0.05);the number of neurons,the con-tents of SOD and GSH,the protein expression of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 were all reduced(P<0.05).Compared with the model control group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expression of ACSL4 and TFR in the Shuanglu Tongnao formula group were reduced(P<0.05),and the number of neurons,the contents of SOD and GSH,the protein expressions of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 are all increased(P<0.05).The results of the SIRT1 inhibitor supplementation experiment showed that the SIRT1 inhibitor reversed the inhibitory effect of Shuan-glu Tongnao formula on neuronal ferroptosis,while also inhibited the expression of Nrf2 and GPx4(P<0.05).Conclusion The Shuanglu Tongnao formula may inhibit neuronal ferroptosis in ischemic stroke rats by activating the SIRT1/Nrf2/GPx4 signa-ling pathway.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Purpose::Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.Methods::Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization.Results::Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. Conclusion::This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.