ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Background Lung cancer, one of the most common malignant tumors worldwide, has long ranked first in cancer incidence and mortality, posing a severe challenge to public health systems. Objective To analyze the trends in incidence, mortality, and disability-adjusted life years (DALYs) of lung cancer among residents in Jing'an District, Shanghai, from 2002 to 2021, explore the impacts of population aging, population growth, and age-specific prevalence on disease burden, and provide a scientific basis for optimizing regional lung cancer prevention and control strategies. Methods Based on the cancer registration and cause-of-death surveillance data of registered residents in Jing'an District, Shanghai, from 2002 to 2021, Joinpoint regression models were used to analyze the annual change trends (APC) and average annual change trends (AAPC) of lung cancer incidence, mortality, DALY rate, and their age-standardized rates. Decomposition analysis was applied to quantify the contribution of population aging, population growth, and age-specific prevalence to changes in the number of new cases, deaths, and DALYs. Results From 2002 to 2021, the crude incidence rate of lung cancer in Jing'an District increased from 68.00 per 100000 to 144.36 per 100000 (AAPC=4.86%, P<0.001), and the age-standardized incidence rate rose from 43.09 per 100000 to 61.46 per 100000 (AAPC=2.89%, P<0.001). The growth rate of incidence was significantly higher in females (AAPC=6.73%) than in males (AAPC=3.62%). The crude mortality rate increased from 58.08 per 100000 to 66.11 per 100000 (AAPC=1.10%, P<0.001), while the age-standardized mortality rate decreased (AAPC=−1.54%, P<0.001). The crude DALY rate showed an upward trend (AAPC=0.94%, P=0.002), whereas the age-standardized DALY rate declined (AAPC=−1.63%, P<0.001). Significant differences were observed across genders and age groups: the mortality and DALY rates increased in males aged 60-64 years, while the fastest incidence growth occurred in females aged 45-64 years. The results of decomposition analysis indicated that the increase in new cases was primarily attributed to age-specific incidence (38.15%) and aging (37.31%); the growth in deaths and DALYs was driven by aging, while age-specific mortality and population growth showed offsetting effects. From 2002 to 2021, the probability of premature death from lung cancer among males (2.04%-2.52%) in Jing'an District showed no statistically significant trend (AAPC=−0.28%, P=0.440), while it presented a decreasing trend in the total population (1.37%-1.89%) and females (0.72%-1.26%) (AAPC=−0.80% and −2.23%, respectively; P=0.029 and <0.001, respectively). Conclusion From 2002 to 2021, the risk of lung cancer incidence in Jing’an District, Shanghai, continue to increase, with a disease burden exhibiting significant heterogeneity by gender and age: key features include a rapid increase in new cases and a trend toward younger onset among females, alongside rising mortality risk among males aged 60–64 years. Population aging and increasing age-specific incidence rates are primary drivers of the growing number of cases, while declining age-specific mortality rates mitigate the rise in mortality burden.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

ObjectiveTo investigate whether Shenmai injection （SMI） improves cisplatin resistance in non-small cell lung cancer （NSCLC） by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups： Blank group， cisplatin group （23.3 μmol·L^-1 cisplatin）， SMI group （20 g·L^-1 SMI）， cisplatin combined with SMI group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI）， cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）， and cisplatin combined with SMI and Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）. Network pharmacology， transcriptomics and metabolomics， Cell Counting Kit-8 （CCK-8） assay， transmission electron microscopy （TEM）， colorimetric assays， and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability， lipid droplet formation， lipid metabolite levels， mitochondrial function， lipid peroxidation， glutathione （GSH） content， total and ferrous iron content， and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells， affecting tumor cell lipid metabolism via autophagy， ferroptosis， and glycerophospholipid metabolism pathways. Compared with the cisplatin group， the cisplatin combined with SMI group showed significantly decreased cell viability （P<0.01）， increased lipid droplet accumulation （P<0.01）， and reduced mitochondrial maximal respiration， basal respiration， mitochondrial membrane potential， GSH content， total iron， and ferrous iron （all P<0.01）. Mitochondrial reactive oxygen species （ROS） was significantly elevated（P<0.01）， and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 （SLC7A11） and p62 （P<0.05，P<0.01） and upregulation of ferritin heavy chain （FTH） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） （P<0.05，P<0.01）. Compared with the cisplatin combined with SMI group， addition of Ferrostatin-1 significantly increased cell viability （P<0.05）， decreased mitochondrial ROS levels （P<0.05）， alleviated mitochondrial shrinkage， and reduced lipid peroxidation. Conversely， addition of Erastin further decreased cell viability （P<0.01）. ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress， which may trigger ferroptosis through upregulation of lipophagy.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

AIM:To investigate alterations in the expression levels of inflammatory cytokines and subsets of CD8+ T cells in the peripheral blood of patients with diabetic retinopathy(DR).METHODS:Retrospective study. A total of 40 patients with type 2 diabetes admitted to Xi'an People's Hospital(Xi'an Fourth Hospital)from April to July 2022 were recruited for this study and categorized into two groups: 20 cases in the simple type 2 diabetes mellitus(DM)group, and 20 cases in the DR group. Additionally, 20 healthy individuals undergoing routine physical examinations served as the control group. The expression levels of cytokines, including interleukin(IL)-6, IL-8, and IL-10 in peripheral blood were quantified using ELISA. Flow cytometry was employed to analyze the expression of programmed cell death-1(PD-1), T cell immunoglobulin domain and mucin domain protein-3(TIM-3), CD28, and CD57 on CD8+ T cells.RESULTS:The peripheral blood expression of IL-6, IL-8, and IL-10 inflammatory cytokines were significantly elevated in DR patients as detected by ELISA(all P<0.001); flow cytometry analysis showed that the expression of PD-1, TIM-3, and CD57 were elevated in peripheral blood CD8+ T cells of DR patients(all P<0.001), and the expression of CD28 was decreased(all P<0.001).CONCLUSION:In DR patients, CD8+ T cells may undergo depletion and senescence as a result of elevated pro-inflammatory cytokines, including IL-6, IL-8, and IL-10.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.