Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Objective To investigate the relationship between the level of hand grip strength(HGS)-based cachexia index(H-CXI)and all-cause mortality in a population with abnormal liver function.Methods The study was based on the America National Health and Nutrition Examination Survey(NHANES)data from 2011～2014,which included 2 752 cases of people with abnormal liver function and followed up until December 31,2019,using Kaplan-Meier survival analysis and COX regression modeling to assess the relationship between H-CXI levels and all-cause mortality,and restricted cubic spline analysis to explore the nonlinear relationship.Results There were 244 all-cause deaths during a mean follow-up time of 82.70±3.86 months.H-CXI was ana-lyzed as a categorical variable(quartiles),and Cox regression analyses showed that in model 2,the risk of all-cause mortality was reduced in groups Q2,Q3 and Q4 compared with group Q1(HR=0.41,95%CI:0.21～0.82,P=0.012 1;HR=0.34,95%CI:0.16～0.69,P=0.003 1;HR=0.24,95%CI:0.09～0.67,P=0.006 3).Subgroup analyses revealed an interaction between stroke and all-cause mortality,and restricted cubic spline revealed a nonlinear relationship between H-CXI levels and all-cause mortality.Con-clusion H-CXI levels are negatively associated with the risk of all-cause mortality in people with abnormal liver function,and attention to H-CXI levels is needed in clinical practice to prevent adverse health outcomes.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective To observe the value of 2D SECara-Net and 3D U2-Net models constructed based on 2D maximal intensity projection(MIP)and 3D time-of-flight MR angiography(3D TOF-MRA)images,respectively,also of their combination for MRA detecting unruptured saccular intracranial aneurysms(USIA).Methods Totally 973 patients with single USIA and 300 subjects who underwent healthy physical examination were retrospectively collected and divided into training set(n=923,containing 723 cases of USIA and 200 healthy subjects)and test set(n=350,containing 250 cases of USIA and 100 healthy subjects)at the ratio of 7:3.Pre-processed 3D TOF-MRA and the obtained 2D-MIP images in training set were imported into 3D U2-Net and 2D SECara-Net models for training and adjusting parameters,respectively.The efficiency of 2 models and their combination for detecting USIA were evaluated.Results The sensitivity,specificity and accuracy of 2D SECara-Net model for detecting USIA in test set was 78.80％(197/250),95.00％(95/100)and 83.43％(292/350),of 3D U2-Net model was 82.80％(207/250),86.00％(86/100)and 83.71％(293/350),respectively.The specificity of 2D SECara-Net model was higher than that of 3D U2-Net model(P=0.030),while no significant difference of sensitivity nor accuracy was found between 2 models(both P＞0.05).The specificity of the combination of the 2 models was 99.00％(99/100),higher than that of 3D U2-Net model(P＜0.05),and the sensitivity and accuracy of the combination was 91.20％(228/250)and 93.43％(327/350),respectivelty,both higher than those of 2 single models(all P＜0.05).Conclusion 2D SECara-Net and 3D U2-Net models had similar,sensitivity and accuracy for MRA detecting USIA.Combination of them could improve the detecting efficacy.

Objective To investigate the relationship between the level of hand grip strength(HGS)-based cachexia index(H-CXI)and all-cause mortality in a population with abnormal liver function.Methods The study was based on the America National Health and Nutrition Examination Survey(NHANES)data from 2011～2014,which included 2 752 cases of people with abnormal liver function and followed up until December 31,2019,using Kaplan-Meier survival analysis and COX regression modeling to assess the relationship between H-CXI levels and all-cause mortality,and restricted cubic spline analysis to explore the nonlinear relationship.Results There were 244 all-cause deaths during a mean follow-up time of 82.70±3.86 months.H-CXI was ana-lyzed as a categorical variable(quartiles),and Cox regression analyses showed that in model 2,the risk of all-cause mortality was reduced in groups Q2,Q3 and Q4 compared with group Q1(HR=0.41,95%CI:0.21～0.82,P=0.012 1;HR=0.34,95%CI:0.16～0.69,P=0.003 1;HR=0.24,95%CI:0.09～0.67,P=0.006 3).Subgroup analyses revealed an interaction between stroke and all-cause mortality,and restricted cubic spline revealed a nonlinear relationship between H-CXI levels and all-cause mortality.Con-clusion H-CXI levels are negatively associated with the risk of all-cause mortality in people with abnormal liver function,and attention to H-CXI levels is needed in clinical practice to prevent adverse health outcomes.

Objective:To analyze the consistency between MT-9000 and IOLMaster 700 in measuring preoperative ocular biometric parameters in patients with age-related cataracts.Methods:A cross-sectional study was conducted.A total of 536 patients (536 eyes) were consecutively included and scheduled for cataract extraction combined with intraocular lens implantation at Aier Eye Hospital of Wuhan University from June 20 to August 22, 2024.Two visualized sweep-frequency biometers, MT-9000 and IOLMaster 700, were used to measure the biometric parameters of all the patients.The parameters including axial length (AL), white to white (WTW), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), and mean keratometry (Km). The AL detection rates of the two instruments were compared, as were the differences in above parameters, and the correlation and consistency of the measurements were analyzed.Patients were divided into three groups based on AL measured by MT-9000: a short axis group (AL<22 mm) comprising 27 eyes, a normal axis group (22≤AL≤25 mm) comprising 392 eyes, and a long axis group (AL>25 mm) comprising 104 eyes.The differences in measured AL in different subgroups were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Aier Eye Hospital, Wuhan University (No.2024IRB06017). Written informed consent was obtained from each subject.Results:The AL detection rate measured by MT-9000 was 99.3% (532/536), higher than 97.6% (523/536) measured by IOLMaster 700, with a statistically significant difference ( χ2=4.841, P=0.028). MT-9000 AL, LT and Km measurements were all higher than IOLMaster 700 measurements, showing statistically significant differences ( Z=6.418, t=4.971, 5.179; all P<0.001). WTW and CCT measurements from MT-9000 were both lower than those from IOLMaster 700, showing statistically significant differences ( Z=-3.017, t=16.322; both P<0.05). After grouping based on AL measurements from MT-9000, there was no statistically significant differences in AL measurements between MT-9000 and IOLMaster 700 in the short axis group and the normal axis group ( Z=-1.530, P=0.126; t=-0.880, P=0.380). In the long axis group, the AL measured by MT-9000 was longer than that by IOLMaster 700, with a statistically significant difference ( Z=7.254, P<0.001). The intra-class correlation coefficient values of AL, WTW, ACD, LT, CCT, and Km measured by MT-9000 and IOLMaster 700 were 1.000, 0.616, 0.997, 0.999, 0.988, and 0.995 (all P<0.001), respectively.The 95% limits of agreement (LoA) of AL, WTW, ACD, LT, CCT, and Km measured by Bland-Altman analysis were -0.06-+ 0.08 mm, -0.64-+ 0.57 mm, -0.06-+ 0.06 mm, -0.04-+ 0.05 mm, -13.6-+ 6.3 μm and -0.26-+ 0.32 D, respectively, which had 6.5%, 3.6%, 5.3%, 6.3%, 6.5% and 4.4% of the data points outside the 95% LoA. Conclusions:MT-9000 shows favorable agreement with IOLMaster 700 in the measurement of AL, ACD, LT, CCT and Km.MT-9000 is suitable for preoperative biometrics measurement in cataract patients.However, the agreement between the two devices is not desirable in the measurement of WTW, and interchangeable use of these two devices is not recommended in this regard.Additionally, MT-9000 outperforms IOLMaster 700 in terms of AL detection rate.

Objective:To analyze the consistency between MT-9000 and IOLMaster 700 in measuring preoperative ocular biometric parameters in patients with age-related cataracts.Methods:A cross-sectional study was conducted.A total of 536 patients (536 eyes) were consecutively included and scheduled for cataract extraction combined with intraocular lens implantation at Aier Eye Hospital of Wuhan University from June 20 to August 22, 2024.Two visualized sweep-frequency biometers, MT-9000 and IOLMaster 700, were used to measure the biometric parameters of all the patients.The parameters including axial length (AL), white to white (WTW), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), and mean keratometry (Km). The AL detection rates of the two instruments were compared, as were the differences in above parameters, and the correlation and consistency of the measurements were analyzed.Patients were divided into three groups based on AL measured by MT-9000: a short axis group (AL<22 mm) comprising 27 eyes, a normal axis group (22≤AL≤25 mm) comprising 392 eyes, and a long axis group (AL>25 mm) comprising 104 eyes.The differences in measured AL in different subgroups were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Aier Eye Hospital, Wuhan University (No.2024IRB06017). Written informed consent was obtained from each subject.Results:The AL detection rate measured by MT-9000 was 99.3% (532/536), higher than 97.6% (523/536) measured by IOLMaster 700, with a statistically significant difference ( χ2=4.841, P=0.028). MT-9000 AL, LT and Km measurements were all higher than IOLMaster 700 measurements, showing statistically significant differences ( Z=6.418, t=4.971, 5.179; all P<0.001). WTW and CCT measurements from MT-9000 were both lower than those from IOLMaster 700, showing statistically significant differences ( Z=-3.017, t=16.322; both P<0.05). After grouping based on AL measurements from MT-9000, there was no statistically significant differences in AL measurements between MT-9000 and IOLMaster 700 in the short axis group and the normal axis group ( Z=-1.530, P=0.126; t=-0.880, P=0.380). In the long axis group, the AL measured by MT-9000 was longer than that by IOLMaster 700, with a statistically significant difference ( Z=7.254, P<0.001). The intra-class correlation coefficient values of AL, WTW, ACD, LT, CCT, and Km measured by MT-9000 and IOLMaster 700 were 1.000, 0.616, 0.997, 0.999, 0.988, and 0.995 (all P<0.001), respectively.The 95% limits of agreement (LoA) of AL, WTW, ACD, LT, CCT, and Km measured by Bland-Altman analysis were -0.06-+ 0.08 mm, -0.64-+ 0.57 mm, -0.06-+ 0.06 mm, -0.04-+ 0.05 mm, -13.6-+ 6.3 μm and -0.26-+ 0.32 D, respectively, which had 6.5%, 3.6%, 5.3%, 6.3%, 6.5% and 4.4% of the data points outside the 95% LoA. Conclusions:MT-9000 shows favorable agreement with IOLMaster 700 in the measurement of AL, ACD, LT, CCT and Km.MT-9000 is suitable for preoperative biometrics measurement in cataract patients.However, the agreement between the two devices is not desirable in the measurement of WTW, and interchangeable use of these two devices is not recommended in this regard.Additionally, MT-9000 outperforms IOLMaster 700 in terms of AL detection rate.

Objective: To analyze the status of outdoor activities on weekends among children and adolescents of different educational stages in Shanghai and their impact on myopia, so as to provide a basis for formulating more specific prevention and control protocol of myopia. Methods: From September to October 2022, a stratified cluster random sampling method was employed to select 84 schools (27 kindergartens, 21 primary schools, 15 junior high schools and 21 high schools) across Shanghai, enrolling a total of 28 654 children and adolescents aged 4 to 18 for the study. Ophthalmic examinations were conducted to ascertain the prevalence of myopia among children and adolescents. Additionally, a questionnaire survey was administered to collect data on outdoor activity duration and associated factors. Multivariate Logistic regression analysis was utilized to investigate the associated factors of outdoor activity levels on weekends. Results: The overall myopia detection rate among children and adolescents was 58.4%, with a higher rate observed in girls (59.2%) compared to boys (57.6%). The myopia detection rates for children and adolescents with an average daily outdoor activity duration of ≥2 h and <2 h on weekends were 54.6% and 68.8%, and the differences were statistically significant ( χ 2=8.12,460.89, P <0.01). Multivariable Logistic regression analysis revealed that girls ( OR =0.80), those with a myopic parent ( OR =0.68), schools from urban districts ( OR =0.72), higher education stages (primary school: OR =0.65, junior high school: OR =0.24, high school: OR =0.14) and spending≥2 h/d on homework during weekends ( OR =0.57) among children and adolescents were less likely to engage in outdoor activities for ≥2 h on weekends ( P <0.01). After incorporating gender, parental myopia status, educational stage, school location, average daily duration on weekends for spending on homework, electronic product usage and outdoor activities as dependent variables in a multivariate Logistic regression analysis, the results showed that children and adolescents with an average outdoor activity duration for ≥2 h on weekends had a lower risk of myopia ( OR =0.86, P < 0.01). Conclusions The level of outdoor activity among children and adolescents on weekends needs to be improved. Outdoor activities on weekends is an associated factor for myopia among children and adolescents. Particularly, girls, those with myopic parents, schools from urban districts, and spending long hours on homework during weekends among children and adolescents require increased attention.

Objective: To investigate the visual acuity and correction conditions of children and adolescents in Shanghai, so as to provide a scientific basis for developing intervention measures to prevent myopia and protect vision among children and adolescents. Methods: From October to December 2022, a stratified cluster random sampling survey was conducted, involving 47 034 students from 16 municipal districts in Shanghai, covering kindergartens (≥5 years), primary schools, middle schools, general high schools and vocational high schools. According to the Guidelines for Screening Refractive Errors in Primary and Secondary School Students, the Standard Logarithmic Visual acuity Chart was used to examine naked vision and corrected vision of students, and general information was collected. The distribution and severity of visual impairment in different age groups were analyzed, and χ 2 tests and multivariate Logistic regression were used to explore factors associated with visual impairment. Results: The detection rate of visual impairment among children and adolescents was 76.2%, with a higher rate among females (78.8%) than males ( 73.8 %), higher among Han ethic students ( 76.2 %) than minority students (71.2%), and higher among urban students (76.7%) than suburban students (75.8%), all with statistically significant differences ( χ 2=162.6, 10.4, 5.5, P <0.05). The rate of visual impairment initially decreased and then increased with age, reaching its lowest at age 7 (53.8%) and peaking at age 17 (89.6%) ( χ 2 trend = 3 467.0 , P <0.05). Severe visual impairment accounted for the majority, at 56.6%, and there was a positive correlation between the severity of visual impairment and age among children and adolescents ( r =0.45, P <0.05). Multivariate Logistic regression showed that age, BMI, gender, ethnicity and urban suburban status were associated with visual impairment ( OR =1.18, 1.01, 1.38 , 0.79, 0.88, P <0.05). Among those with moderate to severe visual impairment, the rate of spectacle lens usage was 62.8%, yet only 44.8 % of those who used spectacle lens had fully corrected visual acuity. Females (64.9%) had higher spectacle lens usage rates than males (60.6%), and general high school students had the highest spectacle lens usage (83.9%), and there were statistically significant differences in gender and academic stages ( χ 2=57.7, 4 592.8, P <0.05). Conclusions The rate of spectacle lens usage among students with moderate to severe visual impairment is relatively low, and even after using spectacle lens, some students still do not achieve adequate corrected visual acuity. Efforts should focus on enhancing public awareness of eye health and refractive correction and improving the accessibility of related health services.