BACKGROUND:The lactate threshold is a crucial physiological indicator for assessing the aerobic metabolic capacity and training level of endurance athletes,representing the intensity point at which lactate production and clearance reach a dynamic equilibrium within the organism.The traditional lactate threshold training,which is a prolonged and stable-intensity training,aims to enhance the aerobic endurance and lactate clearance efficiency of athletes.In recent years,with the advancement of exercise physiology,double lactate threshold training has emerged as an innovative training modality,drawing extensive attention from both the academic circle and practitioners.Nevertheless,current systematic research on double lactate threshold training remains limited,particularly in aspects such as its physiological mechanisms,optimal implementation plans,and long-term effects.OBJECTIVE:To systematically sort out the development course of double lactate threshold training,deeply analyze its fundamental connotations,objectively assess its application effects,and investigate its physiological action mechanisms,with the expectation of providing scientific basis and guidance for the improvement and optimization of endurance sports training theories and practices.METHODS:With the search terms of"lactate threshold training,double lactate threshold training,lactate training,threshold training,endurance training,Norwegian training method,Norwegian training mode,Norwegian training experience,"a systematic search was conducted in databases,including PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang,and VIP.After screening,8articles met the requirements,involving 8 training cases,and 14 top international athletes,and sports events include 800 m,1 500 m,5 000 m,10 000 m,and cross-country running(9.5 km for men and 4.5 km for women).RESULTS AND CONCLUSION:(1)For the first time,double lactate threshold training was defined as a training strategy aimed at improving aerobic and speed capabilities,involving separate aerobic and anaerobic threshold training sessions within a single training day(aerobic training load intensity requirement of 0.7-2.0 mmol/L,anaerobic training load intensity requirement of 2.0-4.5 mmol/L),with a training frequency of＞2 times per week and a training volume of 120-160 km per week.(2)Double lactate threshold training has positive effects on muscle adaptability and plasticity(dimension and elasticity),increasing aerobic and anaerobic capabilities,and alleviating central neural fatigue and peripheral fatigue.(3)The main mechanisms by which double lactate threshold training yields effects may include hormone secretion,protein synthesis and inhibitory regulation,muscle fiber recruitment and cell swelling,mitochondrial biosynthesis and improvement in the chain of respiratory function,and neurotransmitter regulation.(4)In the practical application of double lactate threshold training,factors such as individualized training plans,load intensity design and monitoring for threshold training days,and applicable sports events should be fully considered.For the systematic improvement of double lactate threshold training,further exploration is still needed in terms of application subjects,training plans,action mechanisms,effect evaluation,and safe application.

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:The lactate threshold is a crucial physiological indicator for assessing the aerobic metabolic capacity and training level of endurance athletes,representing the intensity point at which lactate production and clearance reach a dynamic equilibrium within the organism.The traditional lactate threshold training,which is a prolonged and stable-intensity training,aims to enhance the aerobic endurance and lactate clearance efficiency of athletes.In recent years,with the advancement of exercise physiology,double lactate threshold training has emerged as an innovative training modality,drawing extensive attention from both the academic circle and practitioners.Nevertheless,current systematic research on double lactate threshold training remains limited,particularly in aspects such as its physiological mechanisms,optimal implementation plans,and long-term effects.OBJECTIVE:To systematically sort out the development course of double lactate threshold training,deeply analyze its fundamental connotations,objectively assess its application effects,and investigate its physiological action mechanisms,with the expectation of providing scientific basis and guidance for the improvement and optimization of endurance sports training theories and practices.METHODS:With the search terms of"lactate threshold training,double lactate threshold training,lactate training,threshold training,endurance training,Norwegian training method,Norwegian training mode,Norwegian training experience,"a systematic search was conducted in databases,including PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang,and VIP.After screening,8articles met the requirements,involving 8 training cases,and 14 top international athletes,and sports events include 800 m,1 500 m,5 000 m,10 000 m,and cross-country running(9.5 km for men and 4.5 km for women).RESULTS AND CONCLUSION:(1)For the first time,double lactate threshold training was defined as a training strategy aimed at improving aerobic and speed capabilities,involving separate aerobic and anaerobic threshold training sessions within a single training day(aerobic training load intensity requirement of 0.7-2.0 mmol/L,anaerobic training load intensity requirement of 2.0-4.5 mmol/L),with a training frequency of＞2 times per week and a training volume of 120-160 km per week.(2)Double lactate threshold training has positive effects on muscle adaptability and plasticity(dimension and elasticity),increasing aerobic and anaerobic capabilities,and alleviating central neural fatigue and peripheral fatigue.(3)The main mechanisms by which double lactate threshold training yields effects may include hormone secretion,protein synthesis and inhibitory regulation,muscle fiber recruitment and cell swelling,mitochondrial biosynthesis and improvement in the chain of respiratory function,and neurotransmitter regulation.(4)In the practical application of double lactate threshold training,factors such as individualized training plans,load intensity design and monitoring for threshold training days,and applicable sports events should be fully considered.For the systematic improvement of double lactate threshold training,further exploration is still needed in terms of application subjects,training plans,action mechanisms,effect evaluation,and safe application.

GBA1 gene mutation is an important genetic risk factor for Parkinson’s disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient’s motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Purpose To investigate the correlation between molecular typing of urothelial carcinoma(UC)and its clinicopathologic features and prognosis,in order to explore the prognostic markers and therapeutic targets for UC.Methods 115 patients with UC were retrospectively analyzed.Immunohistochemical markers GATA-3,CK20,CK5/6 and CD44 were used for molecular typing of UC(luminal-like type,basal-like type and null).Correlations between molecular typing and clinicopathological features were analyzed using the Chi-square test and Fisher precise test.Sur-vival analysis was performed using the Kaplan-Meier test and Log-rank test.Results The expression of GATA-3 and CK20 was negatively correlated with the clinical stage of UC,while the expression of CD44 was positively correlated with the clinical stage of UC(both P＜0.05).CK20 was a marker of good prognosis(P=0.03).The proportion of clinically advanced UC with basal-like type was significantly higher than that of luminal-like type(78.4％vs 53.4％,P=0.033).Among the histologic variants,UC with neuroendocrine differentiation(100％),sarcomatoid carcinoma(80.0％)and squamous differentiation(77.8％)were basal-like type.All plasmacytoid and lymphoepithelioma-like types,as well as 81.8％of micropapillary UC.Among the null phenotypes,the differential variant predominated(66.7％).Compared with the luminal-like type,although the prognosis of basal-like UC was worse,there was no sta-tistically significant difference(P＞0.05).Conclusion Patients with CK20-expressing UC had a significantly better prognosis.The main histologic variants types of basal-like type and coelomofacial type are different.Molecular typing of UC using immunohistochemical markers is suggestive of clinical staging and prognosis of patients.

Objective To analyze the epidemiological and clinical characteristics of scrub typhus in Liuyang People's Hospital Hunan Province for better diagnosis,treatment,prevention and control of scrub typhus.Methods A retrospective study was conducted on 159 confirmed cases of scrub typhus.The demographic data of patients,clinical manifestations of scrub typhus,laboratory tests,and chest CT findings,complications,treatment,and outcomes were analyzed.Results The 159 patients with scrub typhus included 142 males and 17 females.The average age of patients was(53.8±11.9)(18-82)years old.The peak incidence of scrub typhus was in the period from July to September(87.42％).The common clinical manifestations included fever(97.48％),headache(41.51％),and fatigue(23.90％).The most common signs were eschar(92.45％)on the lower limbs(25.16％),scrotum(15.72％),and buttocks(11.32％).Laboratory test results upon admission showed decreased platelet count(64.15％),elevated creatinine(38.36％),elevated AST(90.57％),ALT(80.50％),and LDH(90.57％).Pulmonary imaging study revealed pulmonary inflammation(22.64％),pleural effusion(13.21％),and pericardial effusion(6.29％).The common complications included liver impairment(69.81％)and decreased platelet count(50.94％),as well as other complications such as renal dysfunction,myocardial injury,sepsis,respiratory failure,and disseminated intravascular coagulation(DIC).Doxycycline-based therapies resulted in cure rate of 98.11％(156/159).Three patients died due to severe complications.Conclusions The peak incidence of scrub typhus was in the period from July to September in Hunan Province.Eschar is a key feature for clinical diagnosis.Scrub typhus can affect multiple organ systems,leading to various systemic complications.The cure rate is high with doxycycline treatment,but some patients may die from severe complications due to delayed medical treatment.

Objective:To observe the effects of Maxing Loushi decoction on the inflammatory response and inflammatory indicators in mice with chronic obstructive pulmonary disease (COPD) models.Methods:Thirty-six BALB/C mice were randomly divided into 4 groups by random number table method: 10 mice in the COPD model group (referred to as the model group), 10 mice in the Maxing Loushi decoction group (referred to as the traditional Chinese medicine group), 10 mice in the programmed death receptor-1 (PD-1) inhibitor group (referred to as the control group), and 6 mice in the normal group. The COPD models of mice in the model group, the traditional Chinese medicine group and the control group were prepared by cigarette smoking combined with lipopolysaccharide (LPS) induction method. During the modeling process, the model group and the traditional Chinese medicine group were respectively given normal saline and Maxing Loushi decoction by gavage. The control group was given intraperitoneal injection of PD-1 inhibitor, while the normal group was given intragastric administration of normal saline. Pathological changes of lung tissues in each group of mice were detected by HE staining. The levels of inflammatory factors [monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)] in the plasma and alveolar lavage fluid (BALF) of mice in each group were determined by enzyme-linked immunosorbent assay (ELISA). The effects of Maxing Loushi decoction intervention on inflammatory responses and inflammatory factors were evaluated.Results:The lung tissue structure in the normal group was basically normal. There was no thickening of the alveolar walls, no infiltration of neutrophils in the tissues, and no obvious inflammatory infiltration. In the model group, the lung tissue structure was slightly abnormal. A small amount of alveolar atrophy could be observed, the alveolar walls were slightly thickened, and inflammatory infiltration could be seen. In the traditional Chinese medicine group, the lung tissue structure was slightly abnormal. A small amount of alveolar atrophy and collapse could be observed, the alveolar walls were not thickened, and individual neutrophil infiltration could be seen in the tissue. In the control group, the lung tissue structure was slightly abnormal, some alveoli atrophied, and a small amount of neutrophil infiltration could be seen in the tissue. The levels of MCP-1 and MIP-1α in plasma and lavage fluid of the model group were significantly higher than those of the normal group (all P<0.05), while the levels of MCP-1 and MIP-1α in plasma and lavage fluid of the traditional Chinese medicine group and the control group were significantly lower than those of the model group (all P<0.05). Moreover, the levels of plasma MCP-1 and MIP-1α in the traditional Chinese medicine group were significantly lower than those in the control group (all P<0.05), while there was no statistically significant difference in the levels of MCP-1 and MIP-1α in alveolar lavage fluid between the traditional Chinese medicine group and the control group (all P>0.05). The levels of IL-6 and TNF-α in plasma and alveolar lavage fluid of the model group were significantly higher than those of the normal group (all P<0.05), while the levels of IL-6 and TNF-α in plasma and alveolar lavage fluid of the traditional Chinese medicine group and the control group were significantly lower than those of the model group (all P<0.05). Moreover, the levels of IL-6 and TNF-α in plasma and alveolar lavage fluid of the traditional Chinese medicine group were significantly lower than those of the control group (all P<0.05). Conclusions:The intervention of Maxing Loushi decoction has a significant improvement effect on the inflammatory response of COPD model mice. Inflammatory factors such as MCP-1, MIP-1α, IL-6, and TNF-α can be used as indicators to determine the degree of COPD inflammation.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

Objective:To investigate the effects of melatonin(MT)on spinal cord ischemia reperfusion injury(SCIRI)and its possible mechanisms in rats.Methods:Forty-two 6-week-old male Sprague Dawley rats were selected for the study and randomly divided into three groups:① Sham group(Sham group,n=14);② model group(model/SCIRI group,n=14);and ③ treatment group(MT group,n=14).Neurological function analysis was used to assess the motor conditions of rats in each group.Nissl staining and hematoxylin eosin(HE)staining were used to observe the number and morphology of neurons in each group,and TUNEL staining was used to evaluate the occurrence of apoptosis of neurons in each group.The expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),gasdermin D(GSDMD),the N-terminal fragment of gasdermin D(GSDMD-N),and cysteine proteinase 1(caspase-1)were evaluated using immunofluorescence,immunohistochemistry staining,and Western blot analysis.Results:Compared with the sham operation group,the neurological function score of the model group was significantly decreased,while the neurological function score of the treatment group was higher than that of the model group(P＜0.05).The model group had fewer Nissl corpuscles compared with that in the sham operation group and abnormal neuronal morphology(P＜0.05).Compared with the model group,the treatment group had a rise in the number of Nissl corpuscles and restored neuronal morphology(P＜0.05).Compared with the Sham group,the number of apoptotic neurons increased in the model group,and the protein expression levels of NLRP3,ASC,GSDMD,and caspase-1 increased(P＜0.05).Compared with the model group,The number of apoptotic neurons and the protein expressions of NLRP3,ASC,GSDMD and caspase-1 in the treatment group were significantly decreased(P＜0.05).Conclusions:MT may alleviate spinal cord ischemia-reperfusion injury by inhibiting pyroptosis in neurons.