Dabuyuanjian is one of the classic famous formulas in the Catalog of Ancient Classic Famous Formulas （Second Batch）-Medicine of Han Ethnic Group. It consists of Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Eucommiae Cortex， Angelicae Sinensis Radix， Corni Fructus， Lycii Fructus， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle， and is used to treat the symptoms of men and women who have a great loss of Qi and blood and a critical and dramatic loss of spiritual guardianship. This study reviewed the ancient and modern literature， and used literature tracing and bibliometrics methods to mine the key information of the historical origin， formula name， drug composition， compatibility， drug dosage， original plants and processing of drugs， decocting method， and clinical application of Dabuyuanjian. The results showed that Dabuyuanjian was first recorded in the Jing Yue's Collected Works （Jing Yue Quan Shu）， with the dosage mainly following the original formula. According to the dosage in the Ming and Qing dynasties， the formula is composed of 5.60 g （for mild cases）/39.17 g （for severe cases） Ginseng Radix et Rhizoma， 7.46 g Dioscoreae Rhizoma， 9.32 g （for mild cases）/ 93.25 g （for severe cases） Rehmanniae Radix Praeparata， 7.46 g Eucommiae Cortex， 9.32 g Angelicae Sinensis Radix， 3.73 g Corni Fructus， 9.32 g Lycii Fructus， and 5.60 g Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. Regarding the original plants of drugs， Ginseng Radix et Rhizoma is produced from the dried roots and rhizomes of Panax ginseng， Dioscoreae Rhizoma from stir-fried dried rhizomes of Dioscorea opposita， Rehmanniae Radix Praeparata from steamed dried roots of Rehmannia glutinosa， Eucommiae Cortex from the dried bark of Eucommia ulmoides， Angelicae Sinensis Radix from the dried roots of Angelica sinensis， Corni Fructus from the dried mature fruit flesh of Cornus officinalis， Lycii Fructus from the dried mature fruits of Lycium barbarum， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle from the honey-processed dried roots and rhizomes of Glycyrrhiza uralensis. These medicinal materials are decocted in 400 mL water to reach a volume of 140 mL， and the decoction should be taken 1 h after meals， 2-3 doses per day. Dabuyuanjian has a wide range of clinical applications， including gynecological and obstetrical diseases， deficiency， baffling and panic， consumptive thirst， and blood， ear， nose， and throat diseases. In modern clinical practice， it is mainly used for diseases of the nervous system， gynecology， urinary system， cardiovascular system， digestive system， musculoskeletal system， connective tissue， immune system， blood， and men. Through the review of ancient and modern literature， this study sorted out the historical evolution and mined the key information of Dabuyuanjian， aiming to provide a theoretical reference for safe and effective clinical application and subsequent research and development of this formula.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

OBJECTIVES: To study the clinical effect of the L-shape technique combined with concentrated growth factor on the horizontal bone defects of maxillary anterior teeth. METHODS: Twenty-five implants from 25 patients who underwent single maxillary anterior tooth implantation with simultaneous bone grafting were selected as the study subjects. Based on the bone grafting techniques, the patients were divided into a test group (L-shaped technique with guided bone regeneration combined with concentrated growth factor, 11 cases) and a control group (traditional guided bone regeneration combined with concentrated growth factor, 14 cases). The early discomfort and wound healing conditions in the two groups at two weeks after surgery were compared. The horizontal bone thickness, vertical bone thickness, and grayscale values in the augmentation area were measured immediately postsurgery and six months after surgery. Implant stability, hard tissue resorption within six months, and grayscale values were compared between the two groups. RESULTS: Differences in early discomfort, wound healing, implant stability, and grayscale values between the two groups were not statistically significant (P>0.05). Vertical bone thickness in the test group was significantly better than that in the control group at six months after surgery (P<0.05). The variation in horizontal bone thickness in the test group was significantly higher than that in the control group (P<0.05). CONCLUSIONS The application of the L-shape technique with concentrated growth factor for horizontal bone defects in the anterior maxillary area yielded satisfactory short-term results in terms of bone augmentation, early discomfort, wound healing, and implant stability at six months after surgery.
Humans ; Maxilla/diagnostic imaging* ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Wound Healing ; Bone Transplantation/methods* ; Dental Implantation, Endosseous/methods* ; Bone Regeneration ; Male ; Female ; Adult ; Dental Implants, Single-Tooth ; Middle Aged

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Combined vaccines can simplify the vaccination process, improve coverage rates, reduce the risk of adverse events following immunization, lower social costs, and improve the timeliness of childhood vaccination. This article focuses on multi-component vaccines based on the diphtheria-tetanus-pertussis containing vaccine. Globally, multiple combined vaccines have been developed and marketed, but the development of combined vaccine is still in its infancy stage in China, with limited vaccine types and doses available. The research, development, and application of combined vaccines still face numerous challenges in China, including technical challenges in research and development, as well as insufficient motivation for research and development. Additionally, the high cost of existing combined vaccines, coupled with low public awareness and weak vaccination intentions, significantly hinders their widespread application, China should continue to rigorously implement the Vaccine Administration Law of the People's Republic of China, promote innovative development of combined vaccines, increase public awareness, strengthen child guardians' confidence in vaccination, and improve the accessibility and affordability of combined vaccines to protect public health across all life stages.

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.