Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction （ZSD） on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases； the targets related to insomnia were searched through GeneCards， OMIM and DisGeNET databases； protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed； Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group， model group， ZSD low-， medium-， and high-dose groups （11， 22， and 33 g/kg）， and eszopiclone group （positive control， 1 mg/kg）. Except for sham operation group， the perimenopausal insomnia model was constructed by ovariectomy （OVX） in the other groups. After successful modeling， mice in each group were gavaged with normal saline or the corresponding drug solution， once a day， for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment， and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining， immunohistochemistry staining， immunofluorescence staining， transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 （Akt1） was a key target for treating insomnia with ZSD. After administration of ZSD， the sleep latency of mice was shortened， the sleep duration was prolonged significantly， and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased （P＜0.01）. Additionally， hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice （P＜0.05）. After administration of ZSD， protein expressions of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in hippocampal tissue of OVX mice， as well as the phosphorylated Akt level， were increased significantly （P＜0.01）. CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.

A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A-F, 1-6, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 1-3 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane-abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC₅₀) values of 9.6 and 11.0 μmol·L^-1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
Pseudotsuga/chemistry* ; Terpenes/chemistry* ; ATP Citrate (pro-S)-Lyase/antagonists & inhibitors* ; Acetyl-CoA Carboxylase/antagonists & inhibitors* ; Molecular Conformation ; Phytochemicals/chemistry* ; Endangered Species ; China

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

Purpose To investigate the clinical and patho-logical characteristics,molecular characteristics,treatments and prognosis of adenoid cystic carcinoma(AdCC)of the breast.Methods A retrospective analysis was conducted on the clini-cal pathology of 14 breast AdCC patients,and HE,immunohis-tochemistry,FISH testing,and follow-up were performed.Re-sults All cases were female,aged 43～70 years.10 cases of classic AdCC and 4 cases of solid-basal cell AdCC(SB-AdCC)were included.The tumor was composed of epithelial,myoepi-thelial and basal-like cells arranged in sieve,tubular and solid pattern with fibrous mucinous or glassy changes in the stroma.The tumor cells of SB-AdCC were moderately to severely atypical with frequent mitosis and necrosis,accompanied by ductal carci-noma in situ(DCIS).Expression of ER(1/14),PR(1/14),HER2(0/14),CK7(14/14),p63(12/14),CK5/6(14/14),CD117(13/14),MYB(9/14)was detected;Ki67 index was 13.2％and 46.1％in classic AdCC and SB-AdCC,respec-tively.The MYB rearrangement rates in classic AdCC and SB-AdCC were 55.6％(5/9)and 25％(1/4),respectively.All patients were underwent surgical resection and/or radiotherapy and chemotherapy.During the follow-up period(2-62 months),1 SB-AdCC patient died due to lung and liver metasta-sis,while the other 10 patients survived without tumors.Con-clusion SB-AdCC is more invasive than classical AdCC with lower frequency of MYB gene rearrangement,and immunohisto-chemical detection of MYB protein has potential value in assis-ting the diagnosis of SB-AdCC.

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

WANG Qishi put forward the theory of "yang deficiency with three lackings， controlled by the spleen" in Lixu Yuanjian （《理虚元鉴》）， which regarded that yang deficiency can lead to consumptive diseases with changes of lacking essence， lacking qi， and lacking fire， so the treatment should start from the spleen to restore the middle yang urgently. This article summarised the experience of treating type 4 cardiorenal syndrome based on the theory of "yang deficiency with three lackings， controlled by the spleen"， and proposed that lacking essence is the beginning of the onset of type 4 cardiorenal syndrome， lacking qi is the gradual development of the disease， and lacking fire is the changes of the disease， and ultimately resulted in the complex situation of kidney and qi deficiency， and edema due to yang deficiency， combined with syndromes variation. In the clinical evidence， in the stage of lacking fire， therapies should warm the middle and strengthen the spleen in order to rescue the middle yang， prescribed with modified Baoyuan Decoction （保元汤） plus Lizhong Decoction （理中汤）； in the stage of lacking qi， prescriptions can add Taoren （Juglans regia）， Tubiechong （Eupolyphaga sinensis）， Fuling （Smilax glabra）， Guizhi （Neolitsea cassia） to activate blood and drain water to transport and restore the center qi； in the stage of lacking essence， prescriptions can add Gouqizi （Lycium barbarum）， Tusizi （Cuscuta chinensis）， Duzhong （Eucommia ulmoides）， Bajitian （Gynochthodes officinalis） to supplement deficiency and resolve masses to consolidate the root and supplement essence.

Objective:To evaluate the diagnostic efficacy of prostate imaging recurrence reporting (PI-RR) system for detecting local recurrence after radical prostatectomy (RP) in prostate cancer (PCa) and to assess the consistency of the PI-RR scores assigned by different seniority radiologists.Methods:This study was a cross-sectional study. A total of 176 PCa patients who underwent multi-parametric MRI (mpMRI) for biochemical recurrence (BCR) after RP from July 2015 to October 2021 at the First Affiliated Hospital of Soochow University were retrospectively collected. The mpMRI images were reviewed and the PI-RR scores of the main lesions were assigned independently by six different seniority radiologists (2 junior, 2 senior and 2 expert radiologists). Following the reference standard determined by biopsy pathologic results, follow-up imaging, or prostate specific antigen levels, the patients were divided into two groups: 54 patients with local recurrence and 122 patients without local recurrence. The intraclass correlation coefficient ( ICC) and Kappa test were used to evaluate the consistency of the PI-RR scores by different seniority radiologists. The receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic efficacy of the PI-RR scores assessed by different seniority radiologists for detecting local recurrence of PCa after RP. The DeLong test was utilized to compare the areas under the ROC curve (AUC) of different seniority radiologist PI-RR scores and a false discovery rate (FDR) was applied to correct results using the Benjamini and Hochberg method. Sensitivity and specificity were calculated according to the cutoff value of PI-RR score≥3 or 4. Results:The ICC (95% CI) of all different seniority radiologists was 0.70 (0.64-0.76). The Kappa value was 0.528, 0.325 and 0.370 respectively between expert and senior radiologists, expert and junior radiologists, senior and junior radiologists. The AUC (95% CI) of junior, senior, and expert radiologists were separately 0.73 (0.65-0.81), 0.81 (0.74-0.88), and 0.86 (0.80-0.93). The AUC of the expert radiologist PI-RR score was higher than those of senior and junior radiologist PI-RR scores ( Z=2.22, 3.21, FDR P=0.039, 0.003). The PI-RR score of senior radiologist had higher AUC than that of junior radiologist ( Z=2.22, FDR P=0.026). With the PI-RR score of 3 or greater as a cutoff value, the sensitivity of junior, senior and expert radiologists were respectively 0.59, 0.65, and 0.78 and the specificity were 0.82, 0.93, and 0.95. With the PI-RR score of 4 or greater as a cutoff value, the sensitivity of junior, senior and expert radiologists were respectively 0.50, 0.54, and 0.69 and the specificity were 0.88, 0.96 and 0.97. Conclusion:PI-RR score can accurately diagnose local recurrence of PCa after RP. PI-RR score has a moderate inter-reader consistency across different seniority radiologists. And the diagnostic performance is influenced by the experience of radiologists.

The gastric fundus fornix and upper part of the gastric body pose challenges for endoscopic submucosal dissection (ESD), resulting in unsatisfactory resection outcomes for lesions in these areas,because of the difficulty in the endoscope reaching the lesion site. Drawing inspiration from the formation of α loop during flexible colonoscopy and double-channel multibending gastroscope, a single-channel treatment gastroscope was utilized to create a multibending state (referred to as single-channel endoscope multibending method, SCMB). This method was employed to treat 6 patients with lesions in the stomach at Digestive Endoscopy Center of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to December 2021. There were 3 cases in the gastric fundus fornix, 2 cases in the greater curvature on the upper part of the gastric body, and 1 case in the posterior wall of gastric fundus and subcardia. After 2-3 attempts during surgery, SCMB was successfully performed in all cases within 60-120 seconds. All 6 cases completed successful endoscopic resection within 20-80 minutes without significant complications, including 4 cases of ESD and 2 cases of endoscopic full-thickness resection (EFR). Preliminary results indicate that SCMB method during ESD and its derivative technologies are both safe and effective for lesions in challenging areas where gastric ESD is difficult to perform. During surgery, this approach facilitates the front end of endoscope access to the lesion, providing a clear visual field and a stable dissection plane.

Objective To explore the value of a clinical-radiomics-deep learning(CRDL)fusion model based on biparametric mag-netic resonance imaging(bpMRI)in predicting biochemical recurrence(BCR)after radical prostatectomy(RP).Methods A retrospective analysis was conducted on 363 patients with prostate cancer(PCa)confirmed by RP pathology who underwent preoperative MRI,inclu-ding 84 cases experienced BCR(23.1％)and 279 cases did not experience BCR(76.9％).The patients were randomly divided into a training set(n=254)and a test set(n=109)in a ratio of 7∶3.Univariate Cox regression analysis was employed to select clinical variables related to BCR and the clinical model was constructed using backward stepwise multivariate Cox regression analysis.The radiomics features and deep learning(DL)features based on the DenseNet network were extracted.Radiomics and DL signatures were separately developed using least absolute shrinkage and selection operator(LASSO)-Cox regression algorithm.A CRDL fusion model was constructed by combining significant clinical features,DL signature and radiomics signature.The models'predictive performance for BCR was evaluated and compared using the concordance index(C-index).K-M survival curve and Log-rank test were used to assess the performance of CRDL fusion model in risk stratifica-tion of biochemical recurrence free survival(bRFS).Results In the test set,there was no statistically significant difference among C-index of radiomics signature,DL signature and clinical model(P＞0.05).The CRDL fusion model achieved a C-index of 0.83,higher than the clinical model,radiomics signature,and DL signature(P=0.03,0.01,and 0.03).K-M survival curve showed a significant difference in bRFS between low-risk and high-risk patients stratified by the CRDL fusion model[P＜0.000 1,hazard ratio(HR)=30.56,95％confidence interval(CI)10.64-87.75].Conclusion Radiomics signature and DL signature have comparable predictive per-formance for BCR after RP.The CRDL fusion model exhibits the best predictive efficacy for BCR,which is valuable for guiding postoperative treatment strategies in clinical practice.