ObjectiveTo analyze the epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases with acute respiratory infections at fever clinics in Huangpu District, Shanghai from 2015 to 2024, and to provide a scientific basis for the prevention and treatment of respiratory diseases. MethodsA retrospective study was conducted in Huangpu District. Individuals meeting the case definition of ILI from 2015 to 2024 was registered. Their nasopharyngeal swabs were collected for pathogen detection. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ResultsFrom 2015 to 2019, a total of 344 ILI cases were tested, of which 192 out of 344 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, 1 557 ILI cases were tested, with 572 out of 1 557 cases (36.74%) being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases was significantly lower than that in 2015‒2019 (χ²=42.66, P<0.001). Specifically, the positive rate of Flu A (χ²=74.43, P<0.001) decreased, while that of HPIV (χ²=8.66, P=0.003) increased, both with statistically significant differences. According to the seasonal pattern, the epidemic intensity of Flu A decreased in summer, while that of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the positive rates of EV/HRV between genders (χ²=22.38, P<0.001), with males exhibiting a higher positive rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ²=4.42, P=0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P<0.05). EV/HRV was more commonly detected in the 15‒<25 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25‒<60 age group (11.26%). 52.63% of cases with co-infections occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A with EV/HRV. ConclusionThe prevalence of respiratory pathogens among ILI cases from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore, influenza surveillance should be strengthened, and attention should also be paid to the prevalence of respiratory pathogens such as HPIV. These findings have profound implications for future research, surveillance, vaccine planning, and public health policy making.

BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

BACKGROUND:Currently,miR-196b-5p has been found to play a role in cell proliferation,migration and inhibition of scar hyperplasia,but there is a lack of relevant studies on whether it plays a role in the process of wound healing.OBJECTIVE:To investigate the effect of miR-196b-5p in adipose stem cell-derived exosomes on burn wound healing.METHODS:The models of deep second degree skin burn in SD rats were established and randomly divided into four groups:blank control group,exosome group,agomiR-196b-5p group,and exosome+antagomiR-196b-5p group,with 10 rats in each group.PBS,adipose-derived stem cell-derived exosomes,miR-196b-5p agonist,and miR-196b-5p inhibitor were injected around the wound according to different groups.Wound healing was observed immediately after injury and on days 7,14,and 21 after injury.On day 7 after surgery,hematoxylin-eosin staining was used to observe the expression of inflammation in the wound surface.On day 14 after suregery,Masson staining was used to observe the expression of collagen and immunohistochemical staining was used to observe the expression of CD31 in the wound surface.On day 7 after surgery,western blot assay was performed to detect the expression of α-smooth muscle actin and type Ⅰ collagen in the wound surface.RESULTS AND CONCLUSION:(1)The wound healing was faster in the agomiR-196b-5p group,while it was slower in the blank control group and the exosome+antagomiR-196b-5p group.(2)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the wound infiltration of inflammatory cells was less in the exosome group and the agomiR-196b-5p group,and the expression of CD31 was significantly increased(P＜0.01).(3)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the expression levels of α-smooth muscle actin and type Ⅰ collagen were increased in the exosome group and the agomiR-196b-5p group(P＜0.05).These findings indicate that miR-196b-5p in adipose stem cell-derived exosomes can promote burn wound healing in rats.

BACKGROUND:Currently,miR-196b-5p has been found to play a role in cell proliferation,migration and inhibition of scar hyperplasia,but there is a lack of relevant studies on whether it plays a role in the process of wound healing.OBJECTIVE:To investigate the effect of miR-196b-5p in adipose stem cell-derived exosomes on burn wound healing.METHODS:The models of deep second degree skin burn in SD rats were established and randomly divided into four groups:blank control group,exosome group,agomiR-196b-5p group,and exosome+antagomiR-196b-5p group,with 10 rats in each group.PBS,adipose-derived stem cell-derived exosomes,miR-196b-5p agonist,and miR-196b-5p inhibitor were injected around the wound according to different groups.Wound healing was observed immediately after injury and on days 7,14,and 21 after injury.On day 7 after surgery,hematoxylin-eosin staining was used to observe the expression of inflammation in the wound surface.On day 14 after suregery,Masson staining was used to observe the expression of collagen and immunohistochemical staining was used to observe the expression of CD31 in the wound surface.On day 7 after surgery,western blot assay was performed to detect the expression of α-smooth muscle actin and type Ⅰ collagen in the wound surface.RESULTS AND CONCLUSION:(1)The wound healing was faster in the agomiR-196b-5p group,while it was slower in the blank control group and the exosome+antagomiR-196b-5p group.(2)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the wound infiltration of inflammatory cells was less in the exosome group and the agomiR-196b-5p group,and the expression of CD31 was significantly increased(P＜0.01).(3)Compared with the blank control group and the exosome+antagomiR-196b-5p group,the expression levels of α-smooth muscle actin and type Ⅰ collagen were increased in the exosome group and the agomiR-196b-5p group(P＜0.05).These findings indicate that miR-196b-5p in adipose stem cell-derived exosomes can promote burn wound healing in rats.

BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

ObjectiveTo explore the mechanism by which Qijia Rougan decoction ameliorates liver fibrosis through amino acid/fatty acid metabolic reprogramming and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway， based on the miRNA-mRNA regulatory network and the interaction between metabolism and signaling pathways. MethodsSprague-Dawley （SD） rats were randomized into four groups （n=8）： control， model， and low-dose and high-dose （7.0， 28.0 g·kg^-1·d^-1， respectively） Qijia Rougan decoction. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCl₄）. From week 9， drug intervention was implemented for 7 weeks. After the final administration， the pathological changes in the liver were evaluated through hematoxylin-eosin （HE） and picrosirius red （PSR） staining. An automated biochemical analyzer was used to measure the serum levels of biochemical indicators， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， albumin （ALB）， and cholesterol （TC）. High-throughput miRNA sequencing was performed to identify differentially expressed miRNAs （DemiRs） during liver fibrosis. A miRNA-mRNA interaction network was constructed to identify key targets， which were then subjected to GO and KEGG enrichment analyses. The expression levels of selected DemiRs were validated by Real-time PCR. ResultsCompared with the control group， the model group showed marked hepatic lobular necrosis， increased collagen deposition， significant fibrosis， elevated serum levels of ALT， AST， ALP， and TBA （P<0.01）， and declined levels of ALB and TC （P<0.01）. Compared with the model group， Qijia Rougan decoction treatment reduced hepatic necrosis， collagen accumulation， and fibrosis， lowered the serum levels of ALT， AST， ALP， and TBA （P<0.01）， and raised the levels of ALB and TC （P<0.01）. Integrated miRNA-seq and RNA-seq analysis identified 31 DemiRs （6 upregulated and 25 downregulated） and 498 targets. The expression trends of four selected DemiRs， including rno-miRNA-376b-3p， were consistent with sequencing results （R²=0.93）. Functional annotation revealed that top 20 upregulated targets were enriched in amino acid and fatty acid metabolism， while top 20 downregulated targets were significantly associated with the PI3K/Akt signaling pathway and cancer progression. ConclusionQijia Rougan decoction alleviates liver fibrosis by reconstructing the miRNA-mRNA regulatory network， promoting metabolic reprogramming， and inhibiting the PI3K/Akt signaling pathway. These findings provide mechanism evidence supporting the multi-targeted antifibrotic effects of traditional Chinese medicine compound formulas.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To analyze the clinical efficacy of intelligent wireless endoscopy in transurethral resection of the prostate, so as to provide evidence for clinical application. Methods A retrospective analysis was conducted on the clinical data of 70 patients with benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate at Tongling People's Hospital during Jan. 2023 and Dec. 2024. Based on the type of endoscopes used, patients were divided into a wireless endoscopy group and a traditional endoscopy group, with 35 patients in either group. Differences between the two groups were compared in terms of surgical preparation time, operation time, postoperative hospital stay, catheter indwelling time, intraoperative blood loss, surgical complications, and operating comfort during the procedure. Results All 70 operations were successfully completed without severe urinary incontinence. The wireless laparoscopy group demonstrated significantly shorter surgical preparation time compared to the traditional laparoscopy group [(12.14±2.39)min vs. (14.89±0.80)min, P＜0.001].There was no statistically significant difference in the operation time between the two groups [(93.51±34.49)min vs. (101.71±34.87)min, P=0.326]. There were no statistically significant differences between the two groups in postoperative hospital stay, catheter indwelling time, intraoperative blood loss, and surgical complications (P＞0.05). The wireless endoscopy group demonstrated significantly higher operating comfort compared to the traditional endoscopy group [(3.94±0.77) vs. (2.57±0.61), P＜0.001]. Conclusion The use of intelligent wireless endoscopy for transurethral resection of the prostate is comparable to traditional endoscopy in surgical efficacy and patient safety, but it can shorten preoperative preparation time and improve operator comfort.