AIM: To investigate the influence of pterygium thickness and area on corneal refractive status.METHODS: Prospective longitudinal study. A total of 60 cases(60 eyes)of pterygium patients admitted to our hospital from January 2024 to September 2024 were randomly selected. All patients underwent pterygium excision combined with pedicle conjunctival flap transplantation for treatment. Optical coherence tomography(OCT)was used to measure the preoperative thickness of patient's pterygium, and a digital slit lamp microscope was used to measure the area of pterygium. The corneal refractive status(degree of corneal astigmatism and average curvature)and changes in uncorrected visual acuity of patients before surgery, 1 d, 1, and 3 mo after surgery were compared. The relationship between preoperative thickness and area of pterygium in patients and corneal refractive status indicators at different postoperative time points were analyzed, and Logistic regression was used to analyze the impact of pterygium thickness and area on postoperative visual improvement in patients.RESULTS: All patients completed follow-up after surgery for 3 mo. At 3 mo after surgery, visual acuity improved in 21 eyes(35%). The results of bivariate Pearson correlation analysis showed that the thickness and area of pterygium positively correlated with the degree of corneal astigmatism and uncorrected visual acuity before surgery and 1 d, 1, and 3 mo after surgery(all P<0.05), and negatively correlated with the average corneal curvature before surgery and 1 d, 1, and 3 mo after surgery(all P<0.05). Logistic regression analysis showed that the thickness and area of pterygium before surgery, high degree of corneal astigmatism, and low uncorrected visual acuity(large LogMAR value)were all risk factors for poor postoperative visual improvement in patients(OR>1, P<0.05). The large average corneal curvature before surgery was a protective factor for poor postoperative visual improvement in patients(OR<1, P<0.05).CONCLUSION: The increase in thickness and area of pterygium can, to some extent, improve corneal astigmatism, reduce the average curvature of the cornea, and affect postoperative visual recovery.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Huanglian Jiedutang （HLJDT） on cognitive function in mice with ischemic stroke （IS） and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB （NF-κB） signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion （MCAO）. Sixty C57BL/6J mice were randomly assigned to five groups （n =12 per group）， i.e.， sham operation， model， HLJDT low-dose （3.9 g·kg^-1·d^-1）， HLJDT high-dose （7.8 g·kg^-1·d^-1）， and Ginkgo biloba extract （GBE， 31.2 mg·kg^-1·d^-1）. Post-operatively， neurological deficit scores （Longa score）， cerebral infarct volume assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and brain water content were evaluated. Learning and memory were assessed using new object recognition （NOR） and fear conditioning （FC） tests. Hippocampal pathology was examined via hematoxylin and eosin （HE） staining. Immunofluorescence detected expression of glial fibrillary acidic protein （GFAP， astrocyte marker）， cellular oncogene Fos （c-Fos， neuronal activation marker）， and glutamate decarboxylase 65 （GAD65）. Western blot measured nuclear factor-κB inhibitor protein α （IκBα）， phosphorylated IκBα （p-IκBα）， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， ionic calcium binding adapter molecule 1 （Iba-1）， tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and apoptosis-related proteins， such as cleaved cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Real-time quantitative PCR （Real-time PCR） was used to assess mRNA levels of Iba-1， TNF-α， IL-1β， NF-κB p65， cleaved Caspase-3， Bax， and Bcl-2. ResultsCompared with the sham group， the model group exhibited significantly increased neurological deficit scores， brain water content， and cerebral infarct volume （P<0.01）. Hippocampal CA1 neurons were disorganized， showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced （P<0.01）. GFAP and c-Fos expression were increased， while GAD65 expression was decreased （P<0.01）. Cleaved Caspase-3 and Bax were upregulated， Bcl-2 was downregulated， and the Bax/Bcl-2 ratio was elevated （P<0.01）. Expression levels of p-IκBα， p-NF-κB p65， IL-1β， TNF-α， and Iba-1 were significantly increased （P<0.01）. Compared with the model group， HLJDT high-dose， low-dose， and GBE groups showed significant improvements in all parameters （P<0.01）. Among them， the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests （P<0.01）. In this group， GFAP and c-Fos decreased， GAD65 increased （P<0.01）， apoptosis-related protein expression was reversed， and NF-κB signaling and related inflammatory factor expression were suppressed （P<0.01）. ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS， potentially by inhibiting the NF-κB signaling pathway， thereby reducing neuroinflammation and hippocampal neuronal apoptosis.

Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

ObjectiveTo investigate the protective effect and mechanism of Wendan Ningxin granules （WNG） on susceptibility to atrial fibrillation （AF） in mice with inflammatory injury. Methods100 C57BL/6 mice were divided into a blank control group， a model group， a low-dose WNG group （2.34 g·kg^-1·d^-1）， a high-dose WNG group （4.68 g·kg^-1·d^-1）， and an amiodarone positive control group （0.091 g·kg^-1·d^-1）， with 20 mice in each group. Except for the blank control group， mice in other groups received intraperitoneal injections of lipopolysaccharide （LPS） to establish an inflammatory injury model. Treatment groups received continuous intragastric administration of their respective interventions for four weeks. During the fourth week， the treatment groups received LPS injections concurrently with their treatments. The blank control and model groups received distilled water （10 mL·kg^-1·d^-1） by gavage， with a gavage volume of 10 mL·kg^-1 for all groups， once daily. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe atrial tissue morphology and fibrosis degree. Immunohistochemistry was used to assess the expression of α-smooth muscle actin （α-SMA） in mouse atrial tissue. Electrophysiological detection was performed using a multi-channel electrophysiology mapping system to measure AF inducibility， AF duration， and atrial effective refractory period （AERP）. High-resolution optical mapping was used to measure action potential duration （APD） dispersion， conduction heterogeneity index， and calcium transient （CaT） dispersion. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of proteins related to diastolic calcium leakage in mouse atria： Ca²⁺/calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）， ryanodine receptor 2（RyR2）， sarco/endoplasmic reticulum Ca²⁺-ATPase （SERCA）， and sodium-calcium exchanger （NCX）. Western blot analysis was performed to detect the expression of CaMKII， RyR2， SERCA， and NCX proteins in myocardial tissue from each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）. ResultsPathological staining results showed that compared with the blank control group， the model group exhibited disrupted atrial tissue structure， inflammatory cell infiltration， atrial fibrosis， and diffuse infiltration of numerous brown α-SMA positive cells in the atrial interstitium （P<0.01）. AF could be induced by electrical stimulation with a longer duration. AERP was shortened， while APD dispersion， conduction heterogeneity index， and CaT dispersion were increased （P<0.01）. The expression of proteins associated with diastolic calcium leakage， including CaMKⅡ， RyR2， and NCX1， showed elevated mRNA and protein levels， whereas SERCA2a mRNA and protein expression decreased （P<0.05）. Serum levels of inflammatory factors IL-1β and TNF-α were elevated （P<0.01）. Compared with the model group， intervention with WNG alleviated cardiac structural damage， reduced inflammatory cell infiltration， improved atrial fibrosis， and reduced the diffuse infiltration of α-SMA positive cells （P<0.01）. AF inducibility and AF duration upon electrical stimulation were significantly reduced （P<0.05）， AERP was prolonged （P<0.05）， mRNA and protein expression of CaMKⅡ， RyR2， and NCX1-proteins associated with diastolic calcium leakage-were reduced， whilst mRNA and protein expression of SERCA2a increased （P<0.05）， and serum levels of IL-1β and TNF-α were decreased （P<0.01）. ConclusionBoth low‑ and high‑dose WNG can effectively reduce susceptibility to inflammation-related AF. The mechanism by which WNG reduce AF susceptibility may be related to regulating proteins involved in sarcoplasmic reticulum diastolic calcium leak， thereby improving cardiac electrical remodeling， and alleviating inflammation-induced myocardial fibrosis， thus improving cardiac structural remodeling.

ObjectiveTo investigate the mechanism of Dipeptidyl peptidase 7 （DPP7） in hepatocellular carcinoma （HCC）. MethodsThe expression of DPP7 protein in hepatocellular carcinoma tissues and liver benign tissues was detected by UALCAN and GEPIA database， immunohistochemical， and Western blot， and its relationship with clinicopathological characteristics was analyzed. The expression of DPP7 was silenced by siRNA and the protein expression of DPP7 in MHCC97H cells was detected by Western blot and qRT-PCR. MTT assay， colony formation assay and wound healing assay were used to detect cell proliferation. Transwell assay was used to detect the invasion and migration ability of cells. Western blot was used to detect the changes of protein markers related to epithelial-mesenchymal transition （EMT）. ResultsIn UALCAN， GEPIA and clinical liver tissue samples， DPP7 expression was upregulated and it was closely related to TNM stage （P=0.002）， lymph node metastasis （P=0.038） and depth of tumor invasion （P=0.027）. The downregulation of DPP7 protein expression in MHCC97H cells was detected after transfection of siRNA in the experimental group （P<0.01）； furthermore， the results of the MTT， colony formation， wound healing and Transwell assay demonstrated that knockdown of DPP7 expression in the MHCC97H cell line significantly inhibited the proliferative and metastatic capabilities of these cells. Consistent with this phenotypic change， analysis of epithelial-mesenchymal transition （EMT） related proteins revealed a significant upregulation of the epithelial marker E-cadherin （P<0.001） and downregulation of the mesenchymal markers Vimentin and N-cadherin （P<0.01）. ConclusionDPP7 is highly expressed in hepatocellular carcinoma tissues and cell lines， and this is associated with poor prognosis in patients. The downregulation of DPP7 protein expression can inhibit the proliferation and metastasis of hepatocellular carcinoma cell line MHCC97H， and its mechanism is closely related to EMT.

ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.