ObjectiveThis paper aims to study the potential active compound components and action mechanism of Shenqi Dihuangtang in the treatment of diabetic kidney disease （DKD） through network pharmacology and in vivo experimental verification. MethodsUltra-high-performance liquid chromatography-Q-exactive orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS） technology was used to clarify the main active chemical components of Shenqi Dihuangtang， and it was combined with network pharmacology methods such as gene ontology （GO） functional annotations and Kyoto encyclopedia of genes and genome （KEGG） to predict the potential action mechanism of Shenqi Dihuangtang in treating DKD. Subsequently， the DKD model of db/db male mice was established， and the mice were randomly divided into model group， low-dose Shenqi Dihuangtang group （6.10 g·kg^-1）， medium-dose Shenqi Dihuangtang group （12.19 g·kg^-1）， high-dose Shenqi Dihuangtang group （24.38 g·kg^-1）， and daplizin group （1.25 mg·kg^-1）. During the same period， C57BL/6J male mice were selected into normal group and received drug intervention for 8 weeks， respectively. During this period， the body weight and fasting blood glucose （FBG） of the mice were dynamically monitored， and oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed at the end of dosing. The levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， uric acid （UA）， albumin （ALB）， and total protein （TP） were measured by an automatic biochemical analyzer， and 24-hour urine protein was measured by a urine protein quantitative kit. Hematoxylin-eosin （HE）， periodic-acid Schiff （PAS）， and Masson staining were employed to observe the renal histopathology. The expression of nephrotic protein Nephrin was observed by immunohistochemistry. Western blot was used to detect the expression of epithelial-mesenchymal transition （EMT）-related proteins such as TGF-β₁， Smad2/3， α-smooth muscle actin （α-SMA）， neural-cadherin （N-Cadherin）， and snail protein. ResultsUPLC-Q-Exactive Orbitrap MS identified 384 active compounds in the aqueous extract of Shenqi Dihuangtang. According to oral bioavailability≥30% and the five drug-like principles， 44 key active ingredients were screened out， and 169 intersection targets highly correlated with DKD were matched. Among them， there was a significant interaction relationship between tumor necrosis factor（TNF）， interleukin（IL）-6， protein kinase B（Akt）1， Caspase-3， Jun proto-oncogene （JUN）， hypoxia inducible factor-1α（HIF-1α）， B cell lymphoma-2（Bcl-2）， matrix metallopeptidase-9（MMP-9）， IL-1β， and TGF-β₁. GO functional annotations were significantly enriched in cellular components such as membrane rafts， membrane microdomains， and collagen-containing extracellular matrix， molecular functions such as DNA-binding transcription factor binding， R-Smad binding， and Smad protein binding， as well as biological processes such as reactions to lipopolysaccharides（LPS）， reactions to bacteria-derived molecules， and wound healing. The KEGG pathway was significantly enriched in lipids and atherosclerosis， TGF-β signaling pathway， phosphatidylinositol 3 kinase （PI3K）/Akt signaling pathway， etc. In vivo experimental results showed that the high-dose Shenqi Dihuangtang group could significantly reduce FBG levels in db/db mice （P<0.01）， improve OGTT （P<0.01） and ITT （P<0.01） levels， reduce SCr （P<0.01）， BUN （P<0.01）， UA （P<0.01） and 24-hour BUN （P<0.01）， and increase ALB （P<0.01） and TP （P<0.01） levels. Pathological staining confirmed that the high-dose Shenqi Dihuangtang group could significantly reduce the glomerular mesangial matrix area and collagen deposition （P<0.01） and upregulate the positive expression rate of Nephrin （P<0.01）. Western blot results showed that the high-dose Shenqi Dihuangtang group significantly downregulated the expression of TGF-β₁ （P<0.01） and Smad2/3 （P<0.01） signal molecules and inhibited the protein levels of α-SMA （P<0.01）， N-Cadherin （P<0.01）， and Snail （P<0.01）. ConclusionShenqi Dihuangtang can inhibit the TGF-β₁/Smad signaling axis and block the renal EMT process， thereby improving DKD renal fibrosis damage. Further analysis of its key active components and clinical transformation pathways is needed in the future.

OBJECTIVE To establish a pharmaceutical management system for externally dispensed medicines in medical institutions， so as to improve medication safety and regulatory efficiency. METHODS Based on policy analysis and hospital practice， a pharmaceutical management system for externally dispensed medicines was constructed by integrating institutional frameworks， an information‑based platform and management procedures， and the management effectiveness was evaluated. RESULTS Our hospital formulated the Regulations on the Management of Externally Dispensed Medicines ， which standardized catalogue selection， prescription issuance， acceptance and use， supervision and evaluation. An information‑based management platform for externally dispensed medicines was built relying on the hospital information system， enabling electronic prescription circulation， intelligent prescription review and whole‑process traceability. Institutional requirements and platform functions were embedded into three core management procedures， namely catalogue selection， prescription issuance， and medicine acceptance and use， forming a closed‑loop working mechanism. After the implementation of the management system， compared with pre‑implementation， the qualified rate of externally dispensed prescriptions increased from 85.2% to 99.3% （ P ＜0.001）， the automatic prescription review pass rate exceeded 95%， the prescription review duration shortened from 7.2 min to 1.8 min （ P ＜0.001）. All dimensional satisfaction scores of patients and medical staff were significantly improved， the standardization awareness of medical staff reached 100%. CONCLUSIONS The construction of a pharmaceutical management system for externally dispensed medicines with standardized institutional frameworks， informatized platforms and standardized procedures effectively enhances the rationality and management efficiency of externally dispensed prescription medicines， and provides a replicable practical pathway for the management of externally dispensed medicines in medical institutions.

ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

Objective:To investigate the clinicopathological characteristics, molecular features, differential diagnosis and prognosis of renal cell carcinoma (RCC) with TFEB gene amplification.Methods:A total of 113 cases of unclassified RCCs and RCCs with TFEB positive expression were collected from the Affiliated Hospital of Qingdao University and Navy 971 Hospital from January 2010 to December 2024. Eight cases of RCCs with TFEB amplification were identified using tissue microarrays, immunohistochemistry, and fluorescence in situ hybridization (FISH) techniques. The clinicopathological data and prognosis of the 8 cases were summarized, and relevant literature was reviewed.Results:Among the 8 cases, there were 5 males and 3 females. The average age was 63.4 (54, 77) year and the median age was 63.5 (59.0, 65.5) year. Seven cases were detected through physical examination, and 1 case presented with initial symptoms of metastasis to bones and lungs. The cohort included 1 biopsy specimen and 7 surgical resection specimens. The tumor diameters ranged from 2.5 to 15.0 cm. The cut surfaces of 5 cases were grayish-yellow or grayish-red, and 2 cases exhibited a colorful appearance, among which 3 cases involved renal sinus and 1 case showed invasion of the perirenal fat tissue. Microscopically, 4 cases were composed of clear cells arranged in solid sheets or acinar structures, along with varying numbers of eosinophilic cells. Two cases exhibited the morphology of high-grade eosinophilic RCC, and 1 case presented biphasic morphology with diffuse polygonal eosinophilic tumor cells and dense small cell components. The remaining 1 case exhibited the morphology of clear cell RCC. According to the WHO/ISUP nuclear grading system, 6 cases were Grade 3 and 2 cases were Grade 2. Multifocal necrosis was observed in 4 cases. In 4 surgical specimens, the tumor tissue invaded the renal parenchyma, with 2 cases showing nodular infiltration to surrounding tissues and 1 case with intravascular tumor thrombus. Immunohistochemical results showed varying degrees of TFEB nuclear positivity in 6 cases (6/8). Melanocytic markers such as Melan A (5/8) and HMB45 (3/8) were expressed at varying degrees. Cathepsin K (6/8), GPNMB (6/8), P504s (7/8) and CD10 (7/8) were positively expressed in most cases. FISH results revealed high-copy amplification of TFEB gene in 4 cases (partially showing clustered amplification) and low-copy amplification in 4 cases. During the follow-up period of 3 to 64 months of the 8 cases, 3 cases metastasized and 2 cases died of disease (both with high-copy TFEB gene amplification).Conclusions:RCC with TFEB gene amplification is rare and exhibits diverse morphological features. A common morphological characteristic of this type of tumor is a mixture of sheet-like clear cells and high nuclear grade eosinophilic cells. Combined immunohistochemical staining for TFEB, melanocytic markers, and GPNMB is helpful for the diagnosis of the tumor, and FISH detection of TFEB gene amplification is the most definitive method in diagnosing this tumor. RCC with TFEB gene amplification usually presents with strong aggressiveness and poor prognosis. Combining surgical resection with immunotherapy or VEGFR-targeted drugs might have therapeutic effects on the tumor.

With the deepening understanding of the pathogenesis of psoriasis, small-molecule drugs targeting the key Janus kinase (JAK) -tyrosine kinase (TYK) 2 pathway have gained increasing interest. TYK2-related pathways play an important role in the pathogenesis of psoriasis, while they are not involved in modulating broad biological effects, making them one of the potential therapeutic targets for the efficient and safe treatment of psoriasis. How to improve the selectivity and specificity of TYK2 inhibitors to minimize adverse reactions associated with the inhibition of other pathways has been one of the key directions for development of drugs targeting TYK2 in recent years. This review summarizes the role of TYK2 pathway in the pathogenesis of psoriasis, the modes of action of TYK2 inhibitors (competitive or allosteric inhibition), and the latest clinical research progress.

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Objective:To analyze the clinical features and diagnostic process of ring chromosome syndrome.Methods:Clinical data of 9 children with ring chromosome syndrome who were treated at the Children′s Medical Center of Peking University First Hospital from September 2009 to May 2025, were summarized and analyzed in a case series study. The data included clinical manifestations, types of epileptic seizures, genetic testing, treatment outcomes, and follow-up results, et al.Results:Among the 9 children with ring chromosome syndrome, there were 6 girls and 3 boys, including 4 children with ring chromosome 20 syndrome, 3 children with ring chromosome 14 syndrome, and 1 child each with ring chromosome 13 and 17 syndrome. All 9 children had de novo chromosomal variations. Among them, 3 children of ring chromosome 20 syndrome were mosaic, and the remaining 6 children were non-mosaic. All 9 children exhibited diverse clinical features, especially those with ring chromosome 20 syndrome, which presented with specific manifestations. The 4 children with ring chromosome 20 syndrome all had acute epileptic seizures as the initial symptom, with onset ages of 67, 39, 17, and 96 months, and all had focal seizures. One child with ring chromosome 20 syndrome had non-convulsive status epilepticus. Development of all 4 children with ring chromosome 20 syndrome was normal before seizure onset, but 3 children showed regression after onset. No physical deformities were observed in 4 children with ring chromosome 20 syndrome, and 2 children were misdiagnosed, 3 children underwent whole exome sequencing and copy number variation analysis in their families, with no abnormalities detected. All 4 children with ring chromosome 20 syndrome were diagnosed through chromosomal karyotype analysis, the intervals between onset and diagnosis were 2, 81, 19 and 13 months, respectively. Follow-up showed that epileptic seizures were not controlled in all 4 children with ring chromosome 20 syndrome. The other 5 children were characterized by developmental delay as the initial symptom, followed by epileptic seizures between 3 and 24 months of age. Developmental regression of the other 5 children did not occur after onset, 2 of them had microcephaly, and 3 had wide-set eyes. No misdiagnoses were reported in these 5 children, and the intervals between onset and diagnosis were 7, 3, 55, 3, and 106 months, respectively. Follow-up showed that epileptic seizures were controlled in these 5 children. Conclusions:Ring chromosome 20 syndrome typically manifest with epilepsy as the initial symptom and are refractory to drug treatment, their early development is entirely normal. Ring chromosome 13, 14, and 17 syndrome are characterized by developmental delay from an early age, followed by the onset of epileptic seizures, which are easily controlled. Conventional whole exome sequencing and copy number variation analysis in families rarely detect ring chromosome abnormalities. Early chromosomal karyotype analysis is essential for the diagnosis of ring chromosome syndrome.

Objective To develop a risk prediction model for ischemic stroke in symptomatic intracranial atherosclerotic stenosis(ICAS)patients based on high-resolution magnetic resonance imaging(HR-MRI)and arterial spin labeling(ASL)imaging.Methods A total of 142 patients were included and divided into acute ischemic stroke(AIS)and transient ischemic attack(TIA)groups based on stroke occurrence.Clinical risk factors,plaque characteristics,and arterial transit artifact(ATA)presence on ASL images were compared between the two groups.Multivariate logistic regression analysis was performed,incorporating clinical risk factors,plaque characteristics,and double post labeling delay(PLD)ATA presence.The predictive value of different models was compared using receiver operating characteristic(ROC)curve and DeLong tests.Results Hypertension,positive lumen remodeling,plaque enhance-ment rate,1.5 s-ATA presence,and 2.5 s-ATA presence were independent risk factors for AIS(P＜0.05).The combination of HR-MRI and ASL imaging predicted AIS most effectively[area under the curve(AUC)=0.908;95％ confidence interval(CI)0.862-0.954].No significant difference was found between the prediction performances of HR-MRI and ASL(95％CI-0.041-0.082,Z=0.659,P=0.509).Conclusion ASL is more convenient than HR-MRI for predicting ischemic stroke in ICAS patients.A model combining plaque characteristics and ATA presence effectively predicts AIS occurrence.

Objective To study the clinical efficacy and safety of detachable titanium clip combined with rubber band intracavity dual traction assistance in endoscopic treatment of gastric submucosal tumors(SMT).Methods 52 patients who underwent endoscopic submucosal excavation(ESE)or endoscopic full thickness resection(EFR)for gastric SMT from January 2022 to July 2024 were selected.27 patients using the detachable titanium clip combined with rubber band intracavity dual traction assistance ESE or EFR were selected as experimental group,and 25 patients using the traditional ESE or EFR were selected as control group.Operation time,hospital stay,hospital cost,one time complete excavation rate and complication rates were compared between the two groups.Results The operation time and hospital stay in the experimental group were significantly shorter than those in the control group,and the hospital cost was also significantly lower,with all differences being statistically significant(P<0.05).The comparison of surgical complication rates between the two groups showed a statistically significant difference(P<0.05),with the experimental group having significantly lower total complication rates than that in the control group.However,there was no statistically significant difference(P>0.05)in the rate of one-time complete excavation between the two groups.Conclusion The detachable titanium clip combined with rubber band intracavitary dual-traction-assisted endoscopic treatment for gastric SMT significantly shortens the operation time and hospital stay,reduces hospital costs and surgical complications.It is a simple,effective auxiliary device that worthy for clinical application.

Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.