Hepatocellular carcinoma （HCC） is a malignant tumor with relatively high incidence and mortality rates worldwide， and its therapeutic resistance and recurrence mechanism are closely associated with liver cancer stem cells （LCSC）. This article systematically introduces the biological characteristics of LCSC and their key role in the progression of HCC， reviews the functional characteristics of the specific surface markers （such as EpCAM and CD133） and related signaling pathways （such as Wnt/β-catenin， TGF-β， and STAT3）， elaborates on the interaction between LCSC and tumor microenvironment， and summarizes the latest clinical treatment strategies targeting LCSC and the countermeasure for existing resistance mechanisms. The article points out that LCSC promote tumor development and progression through metabolic reprogramming and immune microenvironment remodeling， and it is proposed to establish a standardized detection system for LCSC specific markers and promote a triple synergistic therapeutic paradigm combining targeted therapy， immune regulation， and traditional chemotherapy， in order to provide new ideas for the clinical intervention of HCC.

OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

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Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly di-agnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin inter-stitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with ma-chine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50％.In the concentration range of 1 × 10 7 to 1 × 10 10 colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87％.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Objective To investigate the effect of non-alcoholic fatty liver disease(NAFLD)induced by high-fat diet(HFD)on the kidneys of mice and the protective effect and mechanism of Xiayuxue Decoction.Methods A total of 25 healthy controls and 25 NAFLD patients who attended Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2020 to September 2021 were enrolled,and the levels of total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),creatinine(Cr),and uric acid(UA)were measured.A total of 24 male C57BL/6 mice were randomly divided into low-fat diet(LFD)group,HFD group,and HFD+Xiayuxue Decoction group(XYXD group),with 8 mice in each group,and since week 13,XYXD was administered by gavage once a day for 6 weeks till the end of week 18.The level of TC,TG,BUN,and Cr were measured for each group.HE staining and oil red staining were used to observe the pathological changes of the liver and the kidneys;immunohistochemical double staining was used to measure the expression levels of CD68 and alpha-smooth muscle actin(α-SMA);quantitative real-time PCR was used to measure the expression levels of sterol regulatory element binding protein 1(SREBP1),fatty acid synthase(FASN),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),Desmin,and α-SMA in renal tissue;Western blot was used to measure the protein expression levels of SREBP1 and TNF-α.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for pairwise comparison;the independent-samples t-test was used for comparison between two groups.Results Compared with the healthy controls,NAFLD patients showed significant increases in the levels of TC,TG,BUN,Cr,and UA(all P<0.05).Compared with the LFD group,the HFD group had significant increases in body weight,TC,TG,BUN,and Cr(all P<0.001),and compared with the HFD group,the XYXD group showed significant inhibition of the expression of TC,TG,BUN,and Cr(all P<0.001).Liver pathological examination showed that compared with the LFD group,the HFD group showed significant increases in hepatic steatosis and inflammatory infiltration,while the XYXD group showed significant alleviation of lesions.Renal pathological examination showed that compared with the LFD group,the HFD group had significant inflammatory infiltration,steatosis,and collagen formation in renal tissue,and compared with the HFD group,XYXD significantly alleviated inflammatory infiltration and inhibited steatosis and collagen formation.Quantitative real-time PCR showed that compared with the LFD group,the HFD group had significant increases in the relative mRNA expression levels of SREBP1,FASN,IL-6,TNF-α,Desmin,and α-SMA in renal tissue(all P<0.001),and compared with the HFD group,the XYXD group had significant reductions in the relative expression levels of these indicators(all P<0.001).Western blot showed that compared with the LFD group,the HFD group had significant increases in the protein expression levels of SREBP1 and TNF-α(P<0.05),and compared with the HFD group,the XYXD group had significant reductions in the protein expression levels of SREBP1 and TNF-α(P<0.05).Immunohistochemical staining showed that compared with the LFD group,the HFD group had significant increases in the positive staining or the double positive staining of α-SMA and CD68(P<0.05),and compared with the HFD group,the XYXD group showed significant reductions(P<0.05).Conclusion HFD can induce renal steatosis,inflammatory infiltration,and collagen formation,and XYXD might exert a protective effect on the kidneys by inhibiting the expression of macrophages and myofibroblasts in renal tissue.

ObjectiveTo investigate the role and mechanism of podoplanin （PDPN） in hepatic stellate cell （HSC） activation and liver fibrosis. MethodsLiver biopsy samples were collected from 75 patients with chronic hepatitis B who attended Department of Infectious Diseases， Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine， for the first time from September 2019 to June 2022， and RT-PCR and immunohistochemistry were used to measure the expression of PDPN in liver tissue of patients in different stages of liver fibrosis. A total of 12 male C57/BL6 mice were randomly divided into control group and model group. The mice in the model group were given intraperitoneal injection of 10% CCl₄， and those in the control group were injected with an equal volume of olive oil， for 6 weeks. HE staining and Sirius Red staining were used to observe liver histopathological changes； primary mouse liver cells were separated to measure the mRNA expression of PDPN in various types of cells； primary mouse HSCs were treated with PDPN protein， followed by treatment with the NF-‍κB inhibitor BAY11-708， to measure the expression of inflammatory factors in HSCs induced by PDPN. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Spearman correlation analysis was used to investigate data correlation. ResultsAs for the liver biopsy samples， there was a relatively low mRNA expression level of PDPN in normal liver， and there was a significant increase in the mRNA expression level of PDPN in liver tissue of stage S3 or S4 fibrosis （all P<0.001）. Immunohistochemical staining showed that PDPN was mainly expressed in the fibrous septum and the hepatic sinusoid， and the PDPN-positive area in S4 liver tissue was significantly higher than that in S0 liver tissue （t=8.892， P=0.001）. In normal mice， PDPN was mainly expressed in the hepatic sinusoid， and there was a significant increase in the expression of PDPN in CCl₄ model mice （t=0.95， P<0.001）， mainly in the fibrous septum. RT-PCR showed a significant increase in the mRNA expression of PDPN in the CCl₄ model mice （t=11.25， P=0.002）. Compared with hepatocytes， HSCs， Kupffer cells， and bile duct endothelial cells， hepatic sinusoidal endothelial cells showed a significantly high expression level of PDPN （F=20.56， P<0.001）. Compared with the control group， the primary mouse HSCs treated by PDPN protein for 15 minutes showed significant increases in the mRNA expression levels of the inflammation-related factors TNFα， CCL3， CXCL1， and CXCR1 （all P<0.05）， and there were significant reductions in the levels of these indicators after treatment with BAY11-7082 （all P<0.05）. ConclusionThere is an increase in the expression of PDPN mainly in hepatic sinusoidal endothelial cells during liver fibrosis， and PDPN regulates HSC activation and promotes the progression of liver fibrosis via the NF-κB signaling pathway.