Objective To investigate the therapeutic effect of Huangkui capsules on targeted drug-related proteinuria in patients with hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on clinical data of HCC patients with targeted drug-related proteinuria from June 2023 to December 2024 at Zhongshan Hospital, Fudan University. According to the treatment plan, patients were divided into the conventional treatment group and the Huangkui combination treatment group (Huangkui capsules combined with conventional treatment), and the clinical efficacy between the two groups was compared. The logistic regression analysis was used to identify the main factors affecting treatment efficacy. Results The Huangkui combination treatment group (n＝29) showed a significantly higher overall effective rate (79.3% vs 42.3%, P＝0.005), and an earlier proteinuria improvement (median time: 3 months vs 6 months, P＝0.008) than the conventional treatment group (n＝26) . The multivariate logistic regression analysis showed angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker (ARB) using (OR＝0.190, 95%CI 0.045-0.808, P＝0.025), targeted drug adjustment (OR＝0.132, 95%CI 0.030-0.581, P＝0.007), and Huangkui capsules using (OR＝0.168, 95%CI 0.039-0.730, P＝0.017) were protective factors for treatment efficacy of targeted drug-related proteinuria. Conclusions On the basis of conventional treatment, additive treatment with Huangkui capsules can alleviate targeted drug-related proteinuria faster and more effectively in HCC patients.

ObjectiveTo investigate the epidemiological characteristics of human parainfluenza virus (HPIV) in Pudong New Area, Shanghai, and to provide a basis for the prevention and control of HPIV infections in this area. MethodsA total of 8 180 cases with acute respiratory infection (ARI)/influenza-like illness (ILI) attending the fever outpatient clinics, pediatric outpatient clinics, respiratory outpatient clinics, pediatric wards, emergency departments, respiratory wards, and intensive care units (ICUs) and other monitoring departments in 9 sentinel hospitals in Pudong New Area from 2017 to 2022 were selected as the research subjects, and their nasopharyngeal/ throat swabs were collected. Polymerase chain reaction (PCR) method was performed for testing the respiratory virus such as influenza virus, human adenovirus, human parainfluenza virus, respiratory syncytial virus (RSV), human enterovirus, rhinovirus, et al. HPIV serotypes were analyzed, and the detection rates of HPIV were compared between different times, seasons, and population groups. ResultsThe overall HPIV detection rate of ARI/ILI cases in Pudong New Area was 3.73% (305/8 180) in 2017‒2022, with HPIV-3 being the predominant serotype. The detection rate of HPIV decreased significantly in 2017‒2022, peaking at 7.66% (99/1 293) in 2017 and falling to 0.80% (13/1 617) in 2021. Statistically significant differences were observed in HPIV detection rates across different years (χ²_trend=80.037, P_trend<0.001). The detection rate was higher in 2017‒2019 than that in 2020‒2022 (χ²_trend=38.990, P_trend<0.001). HPIV exhibited seasonal patterns in 2017‒2019, with higher detection rates in summer and autumn and lower in spring and winter, whereas no seasonal patterns were observed in 2020‒2022. Children aged <6 years had the highest detection rate (7.07%, 139/1 967), followed by adults aged ≥60 years (4.78%, 85/1 779). Statistically significant differences were observed in the detection rates of HPIV among different age groups (χ²=111.210, P<0.001). Symptoms of HPIV infection were predominantly cough, fever, and runny nose in pre-school children, fever, cough, and sore throat in school-age children, and adults, and cough, expectoration, and fever in the elderly. ConclusionThe HPIV detection rate in Pudong New Area was low in 2017‒2022. The seasonal pattern of HPIV circulation in Pudong New Area disappeared in 2020‒2022 due to the influence of infectious disease epidemics. Young children and the elderly should be prioritized in HPIV prevention and control efforts.

Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

ObjectiveTo investigate the infection characteristics of respiratory syncytial virus (RSV) in children with acute respiratory tract infection (ARI) in Pudong New Area, Shanghai, from 2013 to 2023, so as to provide an evidence for the prevention and control of RSV in Shanghai. MethodsChildren who sought medical care at sentinel healthcare facilities in Pudong New Area, Shanghai, between January 2013 and December 2023 and met the case definition of ARI were included in the study. Nasopharyngeal swab samples were collected and tested for viral pathogens using real-time fluorescene PCR, and the clinical information of whom was collected simultaneously. ResultsA total of 4 980 children were included in the ARI surveillance, among whom 231 tested positive for RSV, with an overall detection rate of 4.64%. Of these, 106 cases were type A and 125 were type B. From 2013 to 2023, the detection rate of RSV in children showed an overall trend of initial increase followed by a decline, with higher detection rates in autumn and winter and lower rates in spring and summer. The RSV detection rate gradually decreased with age, with the highest rate observed in children <1 year old, accounting for 16.33% (80/490) of RSV-detection cases. Cough was the most common clinical symptom. Among the RSV-positive cases, 36 involved co-infection with another virus, 6 co-infected with three viruses, and 1 with mixed infection of four viruses. The most frequent co-infection was RSV and human coronavirus. ConclusionChildren under 1 year of age are more susceptible to RSV infection, with cough being the predominant symptom. RSV infection in Pudong New Area, Shanghai, mainly occurs in winter. Targeted prevention and control measures should be taken for children under 1 year old during the winter season to reduce the risk of both RSV infection and co-infection with human coronavirus and influenza virus.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Objective To investigate the effects of electroacupuncture(EA)at"Baihui(GV 20),""Pishu(BL 20),"and"Zusanli(ST 36)"on the learning and memory functions of rats with Alzheimer's disease(AD)induced by Aβ1-42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF-κ B/NLRP3/Caspase-1 signaling pathway.Methods A rat model of Alzheimer's disease was established by bilateral injection of Aβ1-42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF-grade rats were divided into four groups(n=8 per group):a sham-operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the"Baihui","Pishu",and"Zusanli"acu-points;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF-α and IL-1β.Western blotting and immunofluorescence staining were utilized to assess the co-expression levels of NF-κB p65,NLRP3,and Caspase-1 proteins in the hippocampal region.Results Compared with the sham-operated group,rats in the post-modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF-α and IL-1β were elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were increased(P<0.05).Compared with the model group,rats in both the EA and Western medicine groups showed a trend toward shorter escape latency(P<0.05),increased crossings of the original platform location and time spent in the target quadrant(P<0.05).Cell structures were largely intact,with only a few nuclei showing slight irregularities and some chromatin accumulation at the edges.Serum levels of TNF-α and IL-1β were reduced(P<0.05),and protein expression levels and fluorescence positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were also decreased(P<0.05).Conclusion EA enhances the learning and memory capabilities of AD rats,potentially by downregulating the NF-κ B/NLRP3/Caspase-1+signaling+pathway and decreasing the release of neuroinflammatory factors,thereby alleviating cognitive dysfunction in AD rats.

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.

Objective:To evaluate the diagnostic value of MRI findings in differentiating between tophus and giant cell tumors of the tendon sheath (GCTTS) in the knee.Methods:The study was a case-control study. The clinical and MRI data of patients diagnosed with knee tophus or GCTTS was retrospectively analyzed at the Affiliated Hospital of Qingdao University from September 2018 to September 2024. The study included 23 cases of tophus and 22 cases of GCTTS. MRI sequences, including T 1WI, fat-suppressed T 2WI, and proton density weighted imaging, were evaluated. Parameters including lesion signal intensity and homogeneity, margin, maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, synovial hyperplasia, joint effusion, and periarticular soft tissue swelling were recorded. Independent sample t-tests, χ2 tests, or Fisher exact tests were used to compare MRI findings between the two groups. Multivariate logistic regression was performed to identify independent predictive factors. Results:Significant differences in terms of maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, and periarticular soft tissue swelling between the two groups were found (all P<0.05). No significant differences for other parameters were observed (all P>0.05). Lesion location and ligament/tendon parenchymal involvement demonstrated the highest sensitivity and specificity for distinguishing the two diseases. The sensitivity and specificity values for lesion location were 0.78 and 0.95. The sensitivity and specificity values for ligament/tendon involvement were 0.78 and 1.00. Multivariate logistic regression identified lesion location (inside or outside the synovial cavity) as an independent predictor for differentiating tophus from GCTTS ( OR=31.48, 95% CI 1.58-625.69, P=0.024). Conclusion:The location of the lesion (inside or outside the synovial cavity) and involvement of ligament/tendon parenchyma are critical factors in differentiating knee tophus from GCTTS. Additionally, lesion location serves as an independent predictor for distinguishing between the two conditions.