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.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveThis study employed the scoping review method to systematically retrieve and analyze the basic information and clinical research evidence of expensive Chinese patent medicines （CPMs）， aiming to provide a basis for future related research and clinical applications. MethodsEight Chinese and English databases were systematically searched for the clinical research evidence on expensive CPMs. ResultsEleven expensive CPMs （Angong Niuhuang Wan， Jufang Zhibao Wan， Suhexiang Wan， Pien Tze Huang， Niuhuang Qingxin Wan， Qinggong Shoutao Wan， Compound Realgar Natural Indigo Tablets， Xihuang Wan， Dingkun Wan， Babao Wan， and Guilingji Capsules） were selected. A total of 365 related studies were included in this review， comprising 331 clinical studies （of which 291 were randomized controlled trials）， 30 systematic reviews and Meta-analyses， 3 expert consensus， and 1 rapid health technology assessment. Among the 11 CPMs， 2（Angong Niuhuang Wan and Jufang Zhibao Wan） had a daily price over 500 yuan. The famous and precious Chinese medicinal materials involved included Moschus （frequency of 7）， Bovisc Alculus （7）， and Borneol （5）. The dosage forms included pills， capsules， oral liquid， tablets， and lozenges. The diseases treated by these CPMs mainly included malignant tumors， cerebrovascular diseases， gynecological diseases， and hepatobiliary system diseases. The sample sizes of the clinical studies were mainly concentrated within the range of 51-100 cases， and the main control form was CPM + basic Western medicine treatment vs. basic Western medicine treatment. The 331 clinical studies reported a total of 44 adverse events occurred， of which 36 were determined to be adverse reactions. ConclusionThe scarcity of raw materials leads to the high prices of expensive CPMs. The difficulty of conducting clinical research and the critical and severe cases treated lead to a lack of clinical research evidence with large sample sizes. The uneven distribution of existing studies， incomplete information on medicine package， and non-standard clinical research designs remain to be addressed in the future.

Objective To explore the value of radiomics and deep transfer learning(DTL)based on gadoxetic acid disodium-enhanced magnetic resonance imaging(MRI)for preoperative prediction of microvascular invasion(MVI)in hepatocellular carcinoma(HCC).Methods A retrospective analysis was conducted using the MRI and clinicopathological data of 369 HCC patients who underwent surgery and had pathologically confirmed MVI at the Affiliated Hospital of Qingdao University from January 2019 to September 2024.According to the negative and positive manifestations of MVI,these patients were divided into MVI-group(n=219)and MVI+group(n=150);and they were then randomly assigned into the training set(n=258)and the test set(n=111)in a ratio of 7:3.Based on the hepatobiliary phase images,the optimal features were extracted and screened from radiomics features,DTL features,and the fusion features of the two.Nine machine learning models were constructed using 3 algorithms(random forest,multi-layer perceptron,and support vector machine,separately)and trained on radiomics features,DTL features,and the fusion features of the two.The diagnostic efficacy of each model was evaluated using receiver operating characteristic curve,and the optimal model was identified as the output model.Results Among all the constructed models,those based on fused features outperformed models using individual features.The random forest classifier model in the training set had the best performance,with an AUC of 0.998(95%CI:0.996-1.000),and was therefore selected as the output model in this study.Conclusion Radiomics and DTL models based on gadoxetic acid disodium-enhanced MRI can effectively predict the MVI in HCC.Among these,the random forest classifier model utilizing fused features in the training set exhibits the best performance.

Objective To analyze the reverse mechano-electric effect of the layered structure of articular cartilage and its influencing factors.Methods The cartilage samples were classified according to their physiological thickness(approximately 0.4 mm for the upper layer,1 mm for the middle layer,and 0.6 mm for the lower layer).Through a non-contact external electric field testing method,how different influencing factors affected the reverse mechano-electric effect of articular cartilage was analyzed.Results When the electric field spacing decreased,water content increased,and in vitro time decreased,the displacement of normal layered cartilage in a non-contact electric field increased by 18,10,15 μm,respectively.In the case of simulated arthritis defects,as the defect depth and radius increased,the overall deviation deflection of articular cartilage gradually decreased by about 7 μm.Conclusions The three-layer cartilage differed in their reverse mechano-electricity effects,showing the greatest deflection in the middle layer at 90％water content,under 7 mm electric field spacing,and after 12 hours ex vivo.

Intra-aortic balloon pump(IABP),as the most commonly used percutaneous mechanical circulatory assist device,is routinely implanted through the femoral artery pathway.However,when implantation through the femoral artery pathway is difficult or contraindicated,other pathways including the brachial artery pathway,axillary artery pathway,etc.can be considered.IABP assisted interventional treatment for complex high-risk and indicated patients(CHIP)can reduce the risk of intraoperative complications,stabilize hemodynamics,increase the complete revascularization rate of CHIP,and improve long-term prognosis.The reverse guidewire technique can improve the success rate of percutaneous coronary intervention(PCI)for chronic total occlusion(CTO)of coronary arteries.In clinical practice,the reverse pathway is often chosen in addition to the forward pathway,such as the contralateral radial and brachial artery pathway,femoral artery pathway,etc.This article reports a case of bilateral femoral artery occlusion,in which IABP was implanted through the left brachial artery pathway,and then with the assistance of IABP,the right coronary artery CTO lesion was successfully opened through the right radial artery in the forward direction and the right brachial artery in the reverse direction,with the aim of providing reference for clinical PCI treatment for such special cases.

Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention.Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins.Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05).Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.