The historical development of endogenous wind （内风） is traced with time as the thread， based on the progression of factors such as syndromes， causes of disease， and pathogenesis. It is believed that the concept of wind syndrome originated in The Inner Canon of Yellow Emperor （《黄帝内经》）， encompassing both exogenous wind （外风） and endogenous wind syndrome. Over time， exogenous wind syndrome gradually evolved into mild syndromes and severe syndromes， while endogenous wind syndrome emerged from severe syndromes of exogenous wind. Endogenous wind syndrome has both syndrome and pathogenic attributes， and its theoretical system has gradually become more refined. Based on the theories of ancient and modern medical practitioners， and combining the holistic perspectives with Xiang （象） thinking， it is proposed that endogenous wind has both physiological and pathological distinctions. The physiological endogenous wind refers to the liver's moderate dispersing and regulating function， which helps to distribute qi （气）， blood， and body fluids， while pathological endogenous wind arises from abnormal liver dispersal. Therefore， in clinical practice， different treatment methods， such as tonifying， unblocking， and warming， can be applied according to the differentiation of deficiency and excess in the pathogenesis.

Lactate, with a chemical formula of C₃H₆O₃, is an intermediate product of glucose metabolism in the body and a raw material for hepatic gluconeogenesis. Under physiological resting conditions, the body mainly relies on aerobic oxidation of sugar and fat for energy supply, so the blood lactate concentration is lower. However, during exercise, the enhanced glycolysis in skeletal muscles leads to the significant release of lactate into the bloodstream, causing a marked increase in blood lactate concentration. Traditionally, lactate has been regarded as a metabolic waste product of glycolysis and a contributor to exercise-induced fatigue. Nevertheless, recent studies have revealed that, in humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolism, serving not only as an energy substance alongside glucose but also as a vital component in various biological pathways involved in cardiac energetics, muscle adaptation, brain function, growth and development, and inflammation therapy. Two primary pathways can elevate lactate levels in neurons during exercise. One is peripheral skeletal muscle-derived lactate, which can enter the bloodstream and cross the blood-brain barrier into the brain with the assistance of monocarboxylate transporters (MCTs) from the solute carrier family 16 (SLC16). The other is the central brain-derived pathway. During exercise, neuronal activity is enhanced, promoting the secretion of neuroactive substances such as glutamate, norepinephrine, and serotonin in the brain. This activates astrocytes to break down glycogen into lactate and stimulates glutamate from the presynaptic terminal into the synaptic cleft. It upregulates the glucose transport protein-1 (GLUT-1) expression, allowing astrocytes to convert glucose into lactate through glycolysis. The lactate is produced via peripheral pathways and central pathways during exercise are transported by astrocyte membrane monocarboxylate transporters MCT1 and MCT4 to the extracellular space, where neurons take it up through neuronal cell membrane MCT2. The lactate in neurons can serve as an alternative energy source of glucose for neuronal functional activities, meeting the increased energy demands of synaptic activity during exercise, and maintaining energy balance and normal physiological function in the brain. Additionally, acting as a signaling molecule lactate can enhance synaptic plasticity through the SIRT1/PGC-1α/FNDC5 and ERK1/2 signaling pathways, lactate can promote angiogenesis by upregulating VEGF-A expression through the PI3K/Akt and ERK1/2 signaling pathways, stimulate neurogenesis via the Akt/PKB signaling pathway, and reduce neuroinflammation through activation of the “lactate timer”. Overall, lactate contributes to the protection of neurons, the promotion of learning and memory, the enhancement of synaptic plasticity, and the reduction of neuroinflammation in the nervous system. While lactate may serve as a potential mediator for information exchange between the peripheral and central nervous systems during exercise, further experimental research is needed to elucidate its action mechanisms in the nervous system. In addition, future studies should utilize advanced neurophysiological and molecular biology techniques to uncover the importance of lactate in maintaining brain function and preventing neurological diseases. Accordingly, this article first reviews the historical research on lactate, then summarizes the metabolic characteristics and neuronal sources of lactate, and finally explores the role and mechanisms of exercise-induced lactate in the nervous system, aiming to provide new perspectives and targets for understanding the mechanisms underlying exercise promotion of brain health.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans ; Lung Neoplasms/metabolism* ; Interleukin-5/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Biomarkers ; Immunotherapy ; Disease Progression ; B7-H1 Antigen

OBJECTIVE To explore the safety， effectiveness and cost-effectiveness of a multimodal analgesic regimen in patients who underwent laparoscopic sleeve gastrectomy under the guidance of enhanced recovery after surgery principles. METHODS Data from weight loss patients who underwent laparoscopic sleeve gastrectomy at our hospital were retrospectively collected. The trial group patients received a multimodal analgesic regimen， which included the use of 0.375% ropivacaine for local infiltration of the surgical incision before the end of surgery； intravenous infusion of flurbiprofen axetil 50 mg twice daily； intravenous infusion of methylprednisolone 40 mg once daily and oral administration of extended-release hydrocodone hydrochloride tablets 10 mg twice daily after surgery. The control group patients received a conventional analgesic regimen， which included intravenous infusion of flurbiprofen axetil 100 mg twice daily， with a daily dose twice that of the trial group； and intravenous injection of dexamethasone 5 mg once daily. Propensity score matching was used to balance the baseline data between the two groups. Then the pain scores during movement and at rest at 2， 12， 24 and 36 hours postoperatively， as well as the length of postoperative hospital stay， total length of hospital stay， time to first ambulation after surgery， adverse reactions during hospitalization， total drug costs， and costs of antimicrobial drugs during hospitalization were compared between the two groups. RESULTS The trial group had significantly lower pain scores during movement at 2， 24 and 36 hours postoperatively， and at rest at 2， 12 and 24 hours postoperatively compared to the control group （P＜0.05）. The time to first ambulation after surgery， total length of hospital stay， and length of postoperative hospital stay were significantly shorter in the trial group compared to the control group （P＜0.05）. The incidence of shoulder and back soreness， and costs of antimicrobial drugs were significantly lower in the trial group compared to the control group （P＜0.05）. No statistically significant differences were observed in the total incidence of drug-related adverse reactions and total drug costs during hospitalization between the two groups （P＞0.05）. CONCLUSIONS The multimodal analgesic regimen provides marked pain relief， demonstrates good safety profiles， and has a more economic advantage than the conventional analgesic regimen.

Licorice-gypsum (gancao-shigao, GC-SG) drug pair was used as the research object, using supramolecular chemistry to explore the scientific connotation of combining herbal medicine GC with insoluble mineral medicine SG in clinical application of traditional Chinese medicine. ① The Tyndall effect, microscopic morphology and particle size of the single and co-decocted of GC and SG were observed, the paste content and conductivity were determined, and the interaction between GC and SG was detected by isothermal titration calorimetry (ITC) and infrared absorption spectroscopy (IR). ② Calcium chloride (CaCl₂), a soluble calcium salt of equal gypsum quality, was used instead of SG with GC for co-decocting to explore the effect of calcium salt content on the water decocting, and the characteristics were combined with the Tyndall effect, microscopic morphology, paste content and conductivity. ITC and IR techniques were used to detect the interaction between the two, and the interaction between them was detected by ITC and IR. The zeta potential and ultraviolet-visible spectrophotometry (UV-vis) of GC-SG and GC-CaCl₂ co-decoction were compared, and the inorganic and organic components in the co-decoction were detected by inductively coupled plasma optical emission spectrometer (ICP-OES) and high performance liquid chromatography (HPLC). The results showed: ① Compared with the liquid phase of single decoction, GC-SG co-decoction had more obvious Tyndall effect, and showed uniform spherical nanoparticles under electron microscope. Physical characterization results such as paste content and conductivity showed that co-decoction promoted the dissolution of each other's components; ITC and IR results showed that there was strong interaction between GC and SG, which preliminatively indicated that GC and SG co-decoction promoted the formation of uniform and stable supramolecular system of traditional Chinese medicine. ② When soluble calcium salt was used to substitute insoluble SG with GC for co-decocting, a stronger but astigmatic light path appeared than single decocting solution, the zeta potential was reduced, and a large number of accumulated polymers were formed. The results of paste content and conductivity showed that the dissolution of the co-decocting component was reduced than the single decocting component. ITC, UV-vis and IR results showed that there was interaction between GC with Ca²⁺ and SG. The formation of polysink indicated that a large amount of soluble calcium salt would destroy the stability of supramolecular Chinese medicine. The results of ICP-OES and HPLC showed that the glycyrrhizic acid (GA) content of the former lower than the latter, which was related to the formation of a large number of polycondensates with the increase of Ca²⁺ concentration and the decrease of the dissolution of GA and other active ingredients. This study indicates that the compatibility of GC and SG can form a uniform and stable supramolecular system of traditional Chinese medicine. Calcium salt, the main component of SG, is taken as the starting point. Excessive soluble Ca²⁺ can promote the aggregation of active ingredients such as GA, so as to reveal the scientific connotation of the compatibility of GC and SG, an insoluble mineral medicine.

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

Objective To observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.