Severe acute pancreatitis （SAP） is closely related to dysfunction of the spleen-stomach ascent and descent. Due to the influence of modern lifestyle and dietary factors， Qi deficiency in the spleen and stomach has become the pathological basis of SAP. Its pathogenesis is characterized by dampness， heat， pathogenic factors， stasis， stagnation， obstruction， Fu-organs Qi obstruction， pathogenic excess， and healthy Qi deficiency. At different stages of the disease course of SAP， there is a focus on both pathogenic excess and healthy Qi deficiency. It is specifically manifested as Fu-organs stagnation and heat accumulation， as well as pathogenic excess and healthy Qi deficiency， during the systemic inflammatory response phase， intermingling of blood stasis and pathogenic factors， as well as Qi deficiency and blood stasis， during the infection period， and weakness of the spleen and stomach， as well as healthy Qi deficiency and lingering pathogenic factors， during the residual infection period. Based on the theory that "the spleen and stomach are the acquired foundation"， a staged treatment method centered on the core principle of "strengthening healthy Qi to eliminate pathogenic factors" was developed. The staged treatment method included "clearing the Fu-organs to expel turbidity， replenishing Qi to harmonize the stomach， activating blood circulation to expel pathogenic factors， replenishing Qi to relieve pain， promoting digestion to stimulate appetite， and replenishing Qi to invigorate the spleen". In clinical practice， Hewei Tongxie mixture， Yikang mixture， and Shiwei Jianpi Xiaoshi powder were selected for staged treatment of SAP. This article systematically summarized the theoretical basis of traditional Chinese medicine， Western medicine foundation， modern pharmacological mechanisms， and clinical application experience of the staged treatment of SAP with "strengthening the healthy Qi to eliminate pathogenic factors"， providing new ideas for the treatment of SAP with traditional Chinese medicine.

ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

Objective To evaluate the role of Talin1 in the migration of rat pulmonary artery smooth muscle cells(PASMCs)induced by the serum from rats with hepatopulmonary syndrome(HPS).Methods Twenty male Spra-gue-Dawley(SD)rats were used as HPS rat models by chronic common bile duct ligation,the serum was collected from abdominal aorta.PASMCs were seeded in 6-well and 24-well plates and randomly divided into control group and HPS group.The cells were transfected with Talin1 or control siRNA.The normal rat serum or HPS rat serum with a final concentration of 5％was added respectively.At 24 hours after cell transfection or at 24 hours(T1),48 hours(T2)and 72 hours(T3)of cell incubation,the protein expression of Talin1 and active Integin β1 in PASMCs were determined by Western blot;The migration of PASMCs was measured by Transwell chamber(T1)and scratch assay(T1 to T3).Results Compared to control group,with the extension of the stimula-tion time in the HPS group,the expression of Talin1 protein was upregulated,and the migration of PASMCs was gradually enhanced(P＜0.05);Talin1 siRNA effectively silenced the Talin1 gene;The expression of ac-tive Integin β1 protein and the migration of PASMCs in the HPS group+si control were enhanced(P＜0.05);Compared with the HPS group+si control,the expression of active Integin β1 protein and the migration of PASMCs in the HPS group+siTalin1 were significantly inhibited(P＜0.05).Conclusions Downregulating ex-pression of Talin1 protein inhibits migration of PASMCs and expression of active Integin β1 protein induced by the serum from HPS rats.

Objective To investigate the predictive value of temperature gradients on the mortality of sepsis patients and their correlation with fluid input.Methods By means of a prospective observational method,154 patients with sepsis or septic shock admitted to the Department of Critical Care Medicine at Nanfang Hospital,Southern Medical University from November 2019 to November 2021 were included as research subjects.They were divided into a survivor group(n=118)and a non-survivor group(n=36)according to whether they survived within 28 days.The core-to-toe temperature gradient(CTTG)and toe-to-room temperature gradient(TRTG)were monitored and calculated immediately upon admission to the intensive care unit(ICU)and 6 hours after admission.Receiver operating characteristic(ROC)curve was used to explore the predictive value of temperature gradients on mortality,and multivariate Cox regression analysis was performed to explore the risk factors of 28-day mortality in sepsis patients.The results were verified through survival analysis.Correlation analysis and multivariate analysis of variance were used to explore the correlation between temperature gradients and fluid input,as well as noradrenaline doses.Results Among the 154 patients,118 survived within 28 days(survivor group),and 36 died(non-survivor group).ROC curve and multivariate Cox regression analysis showed that a toe-to-room temperature gradient of≤5.35℃within 6 hours after admission was a risk factor for 28-day mortality.Compared with patients with a high toe-to-room temperature gradient(>5.35℃),patients with a low toe-to-room temperature gradient(≤5.35℃)had a 2.74-fold increase in the risk of 28-day mortality(P=0.004,95%CI 1.54,9.12).The CTTG and TRTG upon admission to the ICU and 6 hours after admission were not significantly associated with fluid input or noradrenaline doses(P>0.05).Conclusions A toe-to-room temperature gradient of less than or equal to 5.35℃within 6 hours after ICU admission is a risk factor for 28-day mortality in sepsis patients.The improvement of temperature gradients at different time points is not associated with fluid input.

Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

Objective To reveal the development characteristics of fat percentage and muscle mass in three nomadic populations in the Hexi Corridor of Gansu.Methods Bioelectrical impedance analysis was used to determine the values of 13 indexes of fat percentage and muscle mass in 263 cases of Gansu Kazakhs,400 cases of Gansu Mongols,and 362 cases of Yugu adults.Results In the three nomadic populations of the Hexi Corridor,visceral fat level of males was significantly positively correlated with age,while total body muscle mass and estimated bone mass were significantly negatively correlated with age.In females,percent body fat,visceral fat grade,percent left and right upper limb fat,percent right lower limb fat and percent trunk fat were all significantly positively correlated with age,while trunk muscle mass was significantly negatively correlated with age.The result of principal component analysis showed that the three nomadic populations in the Hexi Corridor were close to each other in terms of fat percentage and muscle mass characteristics,with high visceral fat grades in males and normal visceral fat grade in females.Among the 13 populations,three nomadic groups in the Hexi Corridor had high fat percentage and muscle mass.Overall,the nomadic population had greater fat percentage and muscle mass than the semi-agricultural and semi-pastoral population,and even more significantly greater than the agrarian population.The long-term integration of the historical Hexi Corridor populations result ed in the relative proximity of the genetic structure of three nomadic populations,which was a genetic factor for the proximity of their fat percentage and muscle mass.Higher per capita disposable income was a socio-economic factor for high fat percentage and muscle mass among Gansu Kazakhs and Gansu Mongolians.Low average annual temperature was an environmental factor for high muscle mass among Gansu Kazakhs and Yugus.Conclusion Gansu Kazakhs,Gansu Mongols,and Yugus have the fat percentage and muscle mass characteristic of northern Chinese populations.

Objective To explore the incidence and its influencing factors of transient severe motion(TSM)in the arterial phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI.Methods The databases of China National Knowledge Network(CNKI),VIP,Wanfang,PubMed,and Embase were searched for studies on the incidence and influencing factors of TSM,and the search time was from the establishment of the databases to October 2024.Meta-analysis was performed via Stata 17.0 software.Results A total of 30 papers(33 studies)were finally included,totaling 12 565 patients.Meta-analysis results showed that the incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI was 13.0％.The risk factors for TSM included age[odds ratio(OR)=1.03;95％confidence interval(CI)1.02-1.05;P＜0.001),chronic obstructive pulmonary disease(COPD)(OR=4.21;95％CI 1.76-10.09;P=0.001),and moderate-to-severe pleural effusion(OR=3.34;95％CI 1.69-6.63;P=0.001),while a previous usage history of Gd-EOB-DTPA(OR=0.56;95％CI 0.39-0.81;P=0.002)was a protective factor of TSM.Conclusion The incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI is relatively high.Age,COPD,moderate-to-severe pleural effusion are risk factors for TSM,while the previous usage history of Gd-EOB-DTPA is a protective factor for TSM.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective To analyze the burden of pressure ulcers and its changing trends among the general population(all age groups)and the elderly aged 65 years and above in China based on the global burden of disease(GBD)data from 1990 to 2021,predict the burden trends from 2022 to 2035,and address the public health issues of its unclear medium-and long-term trends and insufficient precise interventions in its prevention and control in order to provide support for formulating targeted prevention and control strategies.Methods The GBD database was used to extract the incidence,mortality and disability-adjusted life years(DALYs)of pressure ulcers in the general population and in the elderly aged 65 years and above in China from 1990 to 2021.Meanwhile,the age-standardized incidence rate(ASIR),mortality rate(ASMR),and disability-adjusted life rate(ASDR)of the general population were also extracted,and the age-standardized rate(ASRs)corresponding to the elderly population aged 65 years and above were estimated based on the GBD 2021 standard population.The average annual percentage changes(EAPCs)of ASRs were calculated to assess the trends.Bayesian age-period-cohort(BAPC)model was adopted to predict the ASRs and their changing trends of the general and elderly population from 2022 to 2035,respectively.Results From 1990 to 2021,the number of pressure ulcer cases in the general population of China increased from 163 508.67(95%CI:142 891.48～184 055.10)cases to 397 312.27(95%CI:360 058.44～444 875.78)cases,the number of deaths soared from 242.51(95%CI:125.26～702.84)cases to 3 131.54(95%CI:1 562.60～4 126.85)cases,and DALYs increased from 11 965.10(95%CI:7 820.54～21 703.78)to 61 933.91(95%CI:36 313.26～77 402.42).During the same period,the EAPCs of ASIR,ASMR and ASDR were 1.06(95%CI:0.84～1.28),3.63(95%CI:3.45～3.81),and 2.76(95%CI:2.60～2.92),respectively.In 2021,the number of male cases and DALYs were both higher than those of females,while the number of deaths was similar.The ASIR,ASMR and ASDR of the males were all higher than those of the females,and the growth rates of both genders were relatively fast.All indicators were increased significantly with age.It is predicted that by 2035,the ASIR,ASMR,and ASDR in the general Chinese population will continue to rise significantly.From 1990 to 2021,the number of pressure ulcer cases among the elderly(≥65 years old)in China increased from 42 334.95(95%CI:35 739.05～48 930.84)to 238 431.65(95%CI:212 539.53～264 323.77).The number of deaths rose from 204.97(95%CI:93.33～316.60)to 2 871.02(95%CI:2 334.39～3 407.66),and DALYs increased from 4 619.74(95%CI:2 990.73～6 248.76)to 43 968.28(95%CI:37 542.85～50 393.70).The EAPCs of ASIR,ASMR,and ASDR were 2.62(95%CI:2.44～2.80),3.54(95%CI:3.38～3.70),and 3.28(95%CI:3.14～3.42),all of which increased significantly.In 2021,the number of cases,deaths and DALYs among elderly men and women were similar,but the ASIR,ASMR and ASDR of men were all higher than those of women,and their growth rates were faster.It is projected that by 2035,the ASIR of the elderly population will significantly decline to 146.24(95%CI:140.35～152.14),with an EAPC of-0.57(95%CI:-0.64～-0.50),while the ASMR and ASDR will continue to rise and remain higher in males than in females.Conclusion From 1990 to 2021,the number of pressure ulcer cases,deaths and DALYs among the general population and the elderly in China increased significantly,and the ASRs rose rapidly.The burden of pressure ulcers increases significantly with age and is higher in men than in women.Predictions show that ASIR in the general population will continue to rise,while that in the elderly will slightly decline.However,the ASMR and ASDR will continue to increase.Countermeasures Continuously strengthen the prevention and control of pressure ulcers,implement precise intervention for the elderly,especially older men,promote standardized nursing guidelines,enhance training and resource input in primary medical care,and establish a national pressure ulcer monitoring system.

Enzymatic cascade catalysis has emerged as an effective means to enhance the sensitivity of biosensors due to its remarkable amplification effect on electrochemical signals.However,the most used natural enzymes have high specificity and high catalytic activity,but are susceptible to environmental factors,easy denaturation and inactivation,and high cost,which limit their practical applications.Additionally,the majority of nanozymes with excellent catalytic activity cannot be directly used as redox probes.The redox signal can only be required under high potentials in strong acid/alkali solutions,or functionalized with electroactive substances.To tackle this problem,herein,AuNPs(glucose oxidase-like activity)and Mn,Zr dual-doped CeO2 nanozymes(Mn,Zr-CeO2,peroxidase-like activity)were used as model enzymes to construct a high-performance nanozymes cascade catalytic system.Owing to high Ce4+/Ce3+ratio and a considerable number of oxygen vacancies,Mn,Zr-CeO2 nanozymes exhibited excellent peroxidase-like activity and could generate amplified electrochemical signals in neutral medium at low potentials.Furthermore,the porous structure of Mn,Zr-CeO2 nanozymes could accelerate the mass transfer of intermediate H2O2,thereby enhancing the efficiency of enzymatic cascade catalysis.As a result,a label-free electrochemical biosensor was constructed for sensitive detection of the cancer marker miRNA-21 at physiological pH,with a detection limit as low as 32.5 fmol/L.This strategy offered a novel approach for the development of a new generation of high-performance nanozymes cascade platforms,which could be widely applied in the fields such as biotechnology,bioanalysis,and disease diagnosis.