OBJECTIVE To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia （HFIB） and construct a risk prediction model. METHODS A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1， 2020， to December 31， 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method， and goodness-of-fit was evaluated with the Hosmer-Lemeshow test. RESULTS A total of 1 472 patients were included in this study. Of these， 1 445 developed HFIB， yi elding an incidence of 98.17%. Furthermore， 895 were classified as severe HFIB， accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age， high initial dose per 10 kg body weight， use of maintenance dose， and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB， while high baseline fibrinogen （FIB） level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 （95% CI： 0.735-0.785）. The mean absolute error of the calibration curve was 0.006. The P value of the Hosmer-Lemeshow test was 0.609. CONCLUSIONS Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age， high initial dose per 10 kg body weight， use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB， while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.

Gouty arthritis （GA） is caused by monosodium urate（MSU） deposition due to purine metabolism disorders. In traditional Chinese medicine （TCM）， it falls under the category of "dampness-heat Bi syndrome"， with core pathogenesis involving dampness-heat accumulation and dysfunction of the spleen and kidney. The dampness-heat syndrome is the most common and the primary syndrome type during acute attacks. In Western medicine， GA is associated with purine metabolism imbalance and inflammation triggered by MSU crystals， involving pathways such as NOD-like receptor protein 3 （NLRP3） inflammasome activation and Toll-like receptor 2/4 （TLR2/4） signaling. Clinically， colchicine and similar drugs are commonly used to treat GA， although long-term use carries potential side effects. Ermiao Formula analogs originate from ancient prescriptions， including Ermiao， Sanmiao， and Simiao compound formulas. All contain Atractylodis Rhizoma and Phellodendri Chinensis Cortex. Ermiaowan follow a 1∶1 formulation ratio. Sanmiaowan add Cyathulae Radix. Simiaowan further incorporate Coicis Semen. These formulas are rich in active ingredients， including alkaloids， terpenoids， flavonoids， and sterols， and treat GA through multi-component， multi-pathway， and multi-target mechanisms. Ermiaosan primarily exerts anti-inflammatory effects by inhibiting pathways such as TLR4/nuclear factor kappa-B （NF-κB） or regulating immune responses to reduce the release of inflammatory mediators， while also suppressing xanthine dehydrogenase （XDH） and xanthine oxidase （XO） activity to decrease uric acid production. Sanmiaowan enhance uric acid-lowering and anti-inflammatory effects through the guiding herb Cyathulae Radix， while also protecting cartilage from damage. Simiaowan utilizes Coicis Semen to regulate intestinal flora， alleviate dampness-heat symptoms， and exert multi-pathway anti-inflammatory and uric acid-lowering effects. The active ingredients contribute differently to uric acid metabolism regulation， anti-inflammation， antioxidant activity， and bone repair， resulting in varying therapeutic effects due to differences in formula composition. In summary， formulas derived from Ermiaosan demonstrate significant efficacy in treating dampness-heat type GA. This review summarizes their research progress and mechanisms， providing a reference for clinical application， new drug development， and further studies.

OBJECTIVE To investigate the mechanism by which Naozhenning granules （NZN） improve learning and memory impairment in a rat model of multiple cerebral concussion （MCC）. METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group （normal saline）， a model group （normal saline）， a piracetam group （positive control group， 0.324 g/kg）， and high-， medium-， and low-dose NZN groups （5.4， 2.7， 1.35 g/kg）， with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured； Evans blue （EB） extravasation in the cerebral cortex was detected； pathological changes of cortical neurons were observed； the levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the cerebral cortex were determined； and the phosphorylation levels of AMP-activated protein kinase （AMPK）， glycogen synthase kinase 3β （GSK3β）， and Tau protein were detected. RESULTS Compared with the blank group， the model group showed poor mental state， sluggish response to external stimuli， reduced food and water intake， decreased limb flexibility， and disheveled fur. Body weight， sucrose preference rate， and novel object recognition index were significantly decreased （ P ＜0.05）； EB extravasation in the cerebral cortex was significantly increased （ P ＜0.05）， with severe neuronal damage. The positive area ratio of Bax protein， IL-6 and TNF-α levels， and Tau protein phosphorylation level were all significantly increased （ P ＜0.05）， whereas the positive area ratio of Bcl-2 protein， IL-10 level， and AMPK and GSK3β protein phosphorylation levels were significantly decreased （ P ＜0.05）. Compared with the model group， all NZN dose groups showed improvements in general condition and pathological damage， with quantitative indices partially restored， and the differences in quantitative indices in high-dose NZN group were statistically significant （ P ＜0.05）. CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway， inhibiting inflammatory response， reducing Tau protein phosphorylation level， and then repairing the neuronal injury.

Osteoporosis(OP)is a refractory metabolic bone disease,with decreased bone mineral mass,weakened bone strength,and systemic bone pain as typical clinical manifestations.Shenzhen Pingle Guo's Orthopedics,an important branch of the Pingle Guo's Orthopedics,has developed their distinct therapeutic approaches to the prevention and treatment of OP:the fifth-generation inheritor,Mr.Guo Chunyuan,advocated for the simultaneous regulation of qi and blood and formulated Shudi Zhuanggu Formula(composed of Rehmanniae Radix Praeparata,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Poria,Angelicae Sinensis Radix,Paeoniae Radix Alba,Chuanxiong Rhizoma,Dipsaci Radix,and Achyranthis Bidentatae Radix);the sixth-generation inheritor,Professor Yang Zejin,emphasized zang-fu syndrome differentiation and established Yang's Guwei Formula,which simultaneously tonifies the liver,spleen,and kidney,and simultaneously treats deficiency and blood stasis(composed of Astragali Radix,Rehmanniae Radix Praeparata,Achyranthis Bidentatae Radix,Epimedii Folium,Cistanches Herba,Cuscutae Semen,Drynariae Rhizoma,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Corydalis Rhizoma,and Paeoniae Radix Alba);the seventh-generation inheritor,Professor Gong Chunzhu,proposed a three-stage clinical treatment strategy and stressed the principle of reinforcing acquired foundation of life(i.e.,reinforcing spleen and stomach),and formulated the modified Shudi Zhuanggu Formula with Lingnan characteristics(composed of Rehmanniae Radix Praeparata,Corni Fructus,Dioscoreae Rhizoma,Alismatis Rhizoma,Poria,Moutan Cortex,Astragali Radix,Dipsaci Radix,Cyathulae Radix,Acanthopanacis Cortex,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,and Chaenomelis Fructus).During the evolution,Shenzhen Pingle Orthopedic Hospital has continuously integrated modern medical achievements,passed down and enriched the clinical experience,and then the theoretical framework of traditional Chinese medicine in the prevention and treatment of OP has been developed.

Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.

Objective:To evaluate the predictive value of the ROX index and its modified versions for assessing the therapeutic efficacy of high-flow nasal cannula oxygen therapy (HFNC) in pediatric patients with acute hypoxemic respiratory failure (AHRF).Methods:This retrospective study analyzed clinical data from 130 AHRF children admitted to the Pediatric Intensive Care Unit (PICU) of Nanjing Medical University Affiliated Children’s Hospital between January 2020 and December 2024. Patients were categorized into two groups: HFNC success ( n=99) and HFNC failure ( n=31). Clinical parameters were compared between groups, and the predictive performance of the ROX index and its modified variants (ROP, ROXH, ROPH) at various time points was assessed. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for HFNC failure. Results:The HFNC failure group exhibited significantly higher baseline PaCO 2 levels (37.2 mmHg vs. 34.1 mmHg, P<0.05) and prolonged PICU stays (21 days vs. 12 days, P<0.01) compared to the success group. During treatment, the success group demonstrated marked improvements in oxygenation parameters (S/F ratio, P/F ratio) and ROX-derived indices (ROX, ROP, ROXH, ROPH) ( P<0.01). Multivariate analysis identified FiO 2 within 12 hours post-treatment and the ROPH index as independent predictors of HFNC failure ( P<0.05). ROC curve analysis revealed that the relative change in ROPH before and after treatment had the highest predictive accuracy (AUC=0.836, optimal cutoff=0.053, sensitivity=95.3%, specificity=70%) among all evaluated indices. Conclusions:Modified ROX indices, particularly the ROPH index, serve as reliable predictors of HFNC outcomes in children with AHRF. Dynamic monitoring of these indices may enable early identification of patients at risk for treatment failure, facilitating timely clinical intervention.

Abstract: To explore the relationship between the replication-associated bromodomain protein 4 ( BRD4)and human papillomavirus (HPV) 16(HPV16) viral load in cervical squamous cell carcinoma and CIN Ⅰ tissues , confirm the effects of BRD4 degradation agent MZ1 on viral load . Methods : Thirty HPV16-positive cervi- cal cancer specimens and 30 non-cervical cancer specimens were collected , and the viral load of the samples was detected by real-time fluorescence quantitative PCR , and the expression of BRD4 was analyzed by immunohisto- chemistry and Western blot. Results : The viral load was higher in the samples of cervical cancer group than in the samples of non-cancer group , the difference is statistically significant ( P < 0. 01) . Immunohistochemistry results showed that the expression of BRD4 were significantly higher in cervical cancer specimens than in noncancerous specimens , the difference is statistically significant (P < 0. 05) . BRD4 expression was significantly and positively correlated with high viral loads , the difference is statistically significant (P < 0. 001) . the BRD4 degradation agent MZ1 significantly reduced the viral load , the difference is statistically significant (P < 0. 01) . Conclusion BRD4 may be involved in the replication of HPV16 virus , and BRD4 degradation agent MZ1 can inhibit the replication of HPV16 virus .

Objective To observe the effects of electroacupuncture on RhoA/ROCK2 signaling pathway in cerebral cortex of mice with amyotrophic lateral sclerosis(ALS);To explore the mechanism of electroacupuncture in improving the motor function of ALS mice.Methods The male hSOD1G93A mice were divided into model group and electroacupuncture group,and wild-type male mice in the same litter were set as blank group,with 12 mice in each group.After the mice were 60 days old,"Baihui"and both side of"Tianzhu","Tianshu"were selected for electroacupuncture for 10 min per day,5 days of continuous treatment and 2 days off for 3 weeks.Rotating rod experiment and open field experiment were used to evaluate the motor function of mice,the damage of neurons in cerebral cortex was observed by Nissl staining,Western blot was used to detect the expressions of Tar DNA binding protein-43(TDP-43),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,RhoA and ROCK2 protein in cerebral cortex.Immunofluorescence staining was used to detect the positive expressions of ion calcium binding adapter molecule 1(Iba-1)and glial fibrillary acidic protein(GFAP)in cerebral cortex.Results Compared with the blank group,the incubation period of rod turning and the total distance of open field movement in the model group were reduced(P<0.01),the neuron damage was obvious in the cerebral cortex,with Nissl body shrinkage and reduction in quantity(P<0.01),the relative expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 protein increased(P<0.01),and the positive expression of Iba-1 and GFAP increased(P<0.01).Compared with the model group,the incubation period of rod turning and the total distance of open field movement increased in electroacupuncture group(P<0.05),the damage of neuron in cerebral cortex was reduced,the number of Nissl bodies increased(P<0.05),the expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 decreased(P<0.05),and the positive expression of Iba-1 and GFAP reduced(P<0.05).Conclusion Electroacupuncture can improve motor function in ALS model mice,and the mechanism may be related to the inhibition of RhoA/ROCK2 signaling pathway activity and then relieve neuroinflammation.

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

Traumatic brain injury (TBI), as a significant central nervous system damage disease with high frequency in the world, leads to a huge number of patients with impaired health and lower quality of life every year. Lung injury is a common and dangerous consequence, which dramatically raises the mortality of patients. Discovering the pathophysiology of lung injury after TBI and discovering viable therapeutic targets has become an important need for clinical diagnosis and therapy. Neurotransmitters, as the fundamental chemical agents of the nervous system for signal transmission, not only govern neuronal activity and apoptosis in TBI but also significantly influence the pathophysiological mechanisms of lung injury subsequent to TBI. The imbalance is intricately linked to the onset and progression of lung damage. This paper systematically reviews the clinical characteristics and predominant pathogenesis of lung injury following TBI, emphasizing the role of key neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh), in lung injury post-TBI. It examines their influence on inflammatory response, vascular permeability, and pulmonary circulation function. Additionally, the paper evaluates the research advancements and potential applications of targeted therapeutic strategies for various neurotransmitter systems, such as receptor antagonists, transporter inhibitors, and neurotransmitter analogues. This research aims to offer a theoretical framework for clarifying the neural regulatory mechanisms of lung injury following TBI and to establish a basis for the development of novel therapeutic strategies and enhancement of the prognosis of the patients.
Humans ; Brain Injuries, Traumatic/metabolism* ; Neurotransmitter Agents/metabolism* ; Lung Injury/metabolism* ; gamma-Aminobutyric Acid/metabolism* ; Glutamic Acid/metabolism* ; Norepinephrine/metabolism* ; Dopamine/metabolism* ; Acetylcholine/metabolism*