Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

ObjectiveTo analyze the research hotspots and development trends in the field of spinal cord stimulation (SCS) for spinal cord injury (SCI). MethodsLiterature about SCS for SCI was retrieve from the Web of Science (WOS) Core Collection database, with a time range from January, 1999 to July, 2025. VOSviewer 1.6.20 and CiteSpace 6.4.R2 were used to analyze the annual publication volume, countries, authors, institutions, journals and keywords. ResultsA total of 636 literatures were included. From 1999 to 2025, the overall publication trend in this field showed an upward trajectory, with recent years fluctuating but tending to stabilize. The country with the most publications was the United States (429 papers), followed by Russia (98 papers) and China (70 papers). The institution with the highest number of publications was the University of California, Los Angeles (76 papers), the author with the most publications was V. Reggie Edgerton (70 papers), and the journal with the most publications was Journal of Clinical Medicine (31 papers). The most frequently cited study focused on exploring the combination of epidural spinal cord stimulation with task-specific training to restore motor function in patients with complete SCI. Keyword analysis showed that the research hotspots in this field were mainly focused on neuroregulation mechanisms, recovery of motor and autonomic nervous dysfunction, artificial intelligence, closed-loop stimulation and brain-computer interface technology innovations. In recent years, the research focus gradually shifted from basic mechanisms to personalized and precise multifunctional rehabilitation strategies. ConclusionThe field of SCS for SCI has undergone phases of basic mechanism exploration and clinical application expansion. Current research hotspots and future trends focus primarily on the development of new stimulation paradigms and combined innovative technologies.

ObjectiveTo investigate differential metabolites associated with browning in the post-harvest processing of Pinelliae Rhizoma， providing data support for elucidating the key metabolites and metabolic pathways involved in browning， and developing safe and efficient sulfur-free processing techniques. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS） was used to detect the metabolites of Pinelliae Rhizoma at different browning stages（0， 8， 16 h） for widely targeted metabolomics. Subsequently， Multivariate statistical analysis of metabolites was conducted using principal component analysis（PCA）， hierarchical cluster analysis（HCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， and K-means cluster analysis. Differential metabolites at different browning stages were screened based on variable importance in the projection（VIP） value>1 and |log₂fold change（FC）|≥1， and metabolic pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsA total of 1 416 metabolites were identified across the three browning stages of Pinelliae Rhizoma， predominantly comprising amino acids and their derivatives（239）， lipids（219）， alkaloids（156）， phenolic acids（121）， terpenoids（113）， and flavonoids（111）. A two-by-two comparison of the three browning phases， yielded 622 differential metabolites that were significantly enriched in the phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolic pathway. Further analysis revealed that carbohydrates such as D-mannose and turanose， phenolic acids such as 1-O-caffeoyl-6-O-glucosyl-β-D-glucose， dicaffeoylshikimic acid， and flavonoids such as epigallocatechin gallate， vitexin-7-O-rutinoside， luteolin-7-O-（6″-malonyl）glucoside-5-O-arabinoside， catechin gallate， epicatechin gallate， isovitexin-7-O-glucoside-2″-O-rhamnoside， apigenin-7-O-rutinoside-4ʹ-O-sophoroside， 3，5，3ʹ，4ʹ，5ʹ-penta-hydroxyflavan-7-gallate may act as browning substrates and play important roles in the browning process. ConclusionCarbohydrates， phenolic acids， and flavonoids may serve as key substrates in the browning process of Pinelliae Rhizoma， involving pathways such as phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolism， which can provide a theoretical basis for further exploration of the browning mechanism.

Objective To evaluate the protective effect of Schistosoma japonicum cystatin(rSj-Cystatin)in a mouse mode of"two-hit"sepsis.Methods Sixty male C57BL/6 mice randomized equally into sham-operated group,protein group,"two-hit"modeling group,and protein intervention group.In the former two groups,the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later;In the latter two groups,100 μL PBS containing LPS(5 mg/kg)was injected intraperitoneally 24 h before cecal ligation and puncture(CLP),and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP.At 12 h after rSj-Cystatin treatment,6 mice from each group were sacrificed for detection of TNF-α,IL-6,IL-10,TGF-β,iNOS and Arg-1 in the serum,spleen,liver,lung and kidney tissues using ELISA,for examinations of liver,lung and kidney pathologies with HE staining,and for analysis of CD3+CD4+CD25+Foxp3+T cell percentage in the spleen using flow cytometry.The remaining mice were observed for general condition and 72-h survival.Results The 72-h survival rates in the 4 groups were 100％,100％,0％and 20％,respectively,showing significant differences between the latter two groups.The mouse models of"two-hit"sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate,which were significantly ameliorated by rSj-Cystatin treatment.Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+T cell percentage.The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney,and these changes were obviously improved by rSj-Cystatin treatment.Conclusion rSj-Cystatin has a protective effect against"two-hit"sepsis in mice by regulating the inflammatory microenvironment.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.

This study established a droplet digital PCR(ddPCR)EvaGreen assay and probe methods for Schistosoma japonicum detection,and evaluated their application in detecting early infections in the S.japonicum host oncomelania and mice.Primers and corresponding probes for both ddPCR methods were designed and synthesized,and plasmids containing target sequences were constructed.The sensitivity of the two methods was tested through detection of the corresponding plasmids,and infectious and mixed oncomelania genomic DNA.Their specificity was evaluated by the detection of genomic DNA of negative oncomelania,Schistosoma mansoni,Clonorchis sinensis,Spirometra mansoni,and S.japonicum(as a positive control).The ddPCR probe method was evaluated by detection of early infection of oncomelania exposed tomiracidium with various ratios and incubation times,and the early migration and distribution of cercaria or schistosomula in mouse hosts infected with 200 cercaria via abdominal skin contact.According to standard curves constructed through the detection of plasmid serial dilutions,the regression equation for the EvaGreen assay was y=-0.839 9x+7.050 9,with a correlation coefficient R2=0.988 1,and the regression equation for the probe method was y=-1.047 5x+7.255 1,with a correlation coefficient R2=0.999 8.The lowest limit of plasmid detection with the probe method was between 38.94 cp/μL and 194.74 cp/μL.Both methods successfully detected positive reactions in the genomic DNA samples of infectious oncomelania at concentrations above 0.002 ng/μL and in the genomic DNA of each group of oncomelania mixtures.No significant differences between probe methods were observed in the detection values in the control group and the genomic DNA of negative oncomelania,S.mansoni,C.sinensis,and S.mansoni.However,the detection value of genomic DNA of negative oncomelania(291 ng/μL)with the EvaGreen assay was(20.3±4.39)cp/μL,a value significantly higher than the(1.5±0.1)cp/μL observed in the control group.For detection of early infection in oncomelania,the probe method detected Schistosoma japonicum DNA after 30 s incubation at room temperature with a≥5∶1 ratio of miracidium to oncomelania;the detection value peaked after a short time(5 min),and the peak value showed a fold increase similar to the increase in the miracidium to oncomelania ratio.Detection of early stage infection in mice with the probe method revealed that the schistosomula entered the lungs on day 2 and the liver on day 4,and continually migrated within the organs with abundant blood supply(spleen,kidney,and brain)in the first 9 days;moreover,a tendency toward ectopic parasitism was observed in the heart and pancreas on day 9,and a constantly negative control level was observed in the testes.The ddPCR probe method was more accurate and specific than the EvaGreen assay in the detection of plasmids,and infectious and mixed oncomelania,and the latter showed non-specific reactions in negative oncomelania detection.In a practical application,the probe method was demonstrated to be sensitive,to effectively reflect the early infection of oncomelania,and to reveal schistosomula migration and distribution in multiple organs of infected mice.

Natural products are an important source for innovative drugs,but unclear molecular targets and mechanisms limit their further development and application.The authors proposed a new method for the target identification of natural products based on proteolysis-targeting chimera(PROTAC)technology and quantitative proteomics,and established the targeted degradomics(TGDO) technology for the identification of weak-affinity tar-gets.This article summarizes the standardized workflow and the application of TGDO for target identification of natural products.

Mycoplasma pneumoniae pneumonia(MPP)was a respiratory disease caused by mycoplasma pneumoniae(MP),with a complex and diverse pathogenesis involving multiple modes of cell death.Recent studies showed that programmed cell death(PCD)was associated with MPP.PCD includes cell apoptosis,necrotic apoptosis,autophagy,pyroptosis,extracellular capture network,iron death,and copper death.Therefore,it was of great significance to have a deep understanding of various PCD mechanisms and their relationship with MMP,and to analyze the role of PCD in the occurrence and development mechanism of MMP.This article aims to elucidate the latest developments in PCD research in MPP,to analyze the specific role of PCD in disease progression,and to explore their potential as therapeutic targets.In order to provide theoretical basis and practical direction for optimizing the diagnosis and treatment of MPP,and also to indicate the direction for the development of new target drugs.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.