OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Inflammation is the body’s response to damage， infection or other stimuli， but its excessive or continuous development can lead to a variety of diseases. Although modern medical anti-inflammatory therapies were widely used， it is often accompanied by limitations such as more adverse reactions. Based on the “holistic view” and “differential treatment”， traditional Chinese medicine （TCM） regards inflammation as a manifestation of the imbalance of yin and yang in the body and the conflict between good and evil. The application of anti-inflammatory TCM is not only aimed at the pathological state of “inflammation”， but also based on the overall consideration of “syndrome”. According to different types of syndrome， anti-inflammatory TCM can be divided into heat-clearing and detoxifying agents （such as Lonicera japonica and Isatis indigotica ）， heat-clearing and drying dampness agents （such as Coptidis Rhizoma）， blood-activating and stasis-dissolving agents （such as Salvia miltiorrhiza ） and vital qi-strengthening and pathogenic factor-expelling agents （such as Panax ginseng ）. Four types of anti-inflammatory TCM restore the body’s immune balance through the systematic regulation of multi-component， multi-target and multi-pathway， exhibiting a good anti-inflammatory effect. Future research should focus on integrating systematic biology， applying artificial intelligence， carrying out high-quality evidence-based research， and combining traditional Chinese medicine and Western medicine， so as to reveal the overall regulatory law of anti-inf lammatory effects of TCM and promote clinical rational use.

OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection （LR） on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group， LR group， and 5， 20， 50 mg/kg mesaconate+LR groups， with 20 rats in each group， to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection， rats in the shock group received no resuscitation， while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control， fluid infusion volume， blood loss rate and survival status were observed in each group. Rats were further divided into the normal group， shock group and mesaconate （50 mg/kg）+LR group， with 10 or 20 rats in each group， to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group， the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group， after 3 h of low-pressure resuscitation， bleeding control was performed by ligation of the spleen artery， and the infusion volume and blood loss rate were recorded； subsequently， the rats received LR resuscitation with twice the volume of blood loss. Then， blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates， indicators related to sublingual microcirculatory perfusion， liver and kidney blood flow， indicators related to the function of vital organs， and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure （MAP） within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h， with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group， compared to the LR group （ P ＜0.05）. In the LR group， rats maintained low pressure for up to 1 hour with a survival rate of 52.94%， and no rats survived beyond 2 h. In the 5， 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 1 h with a survival rate exceeding 80%； in the 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR， the 72 h survival rate of rats was 43.75%， and significant improvements in blood gas parameters were observed compared to the end of the shock phase （ P ＜0.05）. Compared to the shock group， the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators， and liver/kidney blood flow after complete resuscitation （ P ＜0.05）， with significant reductions in heart， liver and kidney function-related indicators and lung water content （ P ＜0.05）. CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions， improves blood gas parameters， sublingual microcirculatory perfusion， and liver/kidney blood flow， mitigates vital organ impairment and pulmonary edema， and increases the survival rate of shocked rats.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

AIM:To observe the changes of Th17 related cytokines in tears of conjunctivochalasis(CCH)patients with liver-kidney yin deficiency treated with traditional Chinese medicine Qi Jing Mingmu decoction combined with artificial tears.METHODS:A total of 56 CCH patients(56 eyes)with liver-kidney yin deficiency of grade Ⅱ to Ⅲ were collected and randomly divided into treatment group(treated with Qi Jing Mingmu decoction combined with artificial tears)of 26 cases(26 eyes)and control group(treated with pure artificial tears)of 30 cases(30 eyes). The treatment course was 1 mo, and international ocular surface disease index(OSDI), tear film break-up time(BUT), tear meniscus height(TMH)and conjunctival congestion index of the patients were observed before and after treatment. The patients' tears were collected before and after treatment, and Th17 related cytokines in tears were detected using flow cytometry immunofluorescence luminescence method.RESULTS:After treatment, the OSDI, BUT and conjunctival congestion index of CCH patients in the treatment group and control group were significantly improved(all P<0.01). After treatment, the TMH of CCH patients in the treatment group was significantly reduced(P<0.01), while there was no statistically significant difference in TMH of the control group before and after treatment(P=0.41). After treatment, the levels of Th17 related cytokines IL-17A, IL-22, IFN-γ, IL-17F, and IL-1β in tears of CCH patients in the treatment group were significantly reduced after treatment(all P<0.01), and the changes in the treatment group were more significant(all P<0.05). There was no significant difference in the control group before and after treatment(all P>0.05). After treatment, the levels of IL-6 and TNF-α in the tears of both groups of CCH patients decreased compared to those before treatment(both P<0.05), but the changes in the treatment group were more significant(both P<0.01).CONCLUSION:Qi Jing Mingmu decoction combined with artificial tears can effectively improve the ocular surface microenvironment, enhance tear film stability, and inhibit ocular surface inflammation in CCH patients with liver-kidney yin deficiency. This may be related to its reduction in the secretion of Th17 related cytokines in tears.

Objective To evaluate the safety and efficacy of total arterial off-pump coronary artery bypass grafting (OPCABG) using a left internal thoracic artery (LITA) combined with bilateral radial arteries (RAs). Methods We retrospectively analyzed the clinical data of patients with severe multi-vessel coronary artery disease who underwent total arterial OPCABG with a LITA and bilateral RAs at Sichuan Provincial People’s Hospital from November 2020 to April 2023. Results A total of 24 patients were included, comprising 23 males and 1 female, with a mean age of (53.63±4.33) years. The New York Heart Association (NYHA) functional class was Ⅱ to Ⅲ. The mean number of distal anastomoses was 3.17±0.38. A Y-graft was constructed in 12 patients and sequential grafting was performed in 4 patients. Concomitant procedures included coronary endarterectomy in 1 patient, intra-aortic balloon pump (IABP) implantation in 10 patients, and thymoma resection in 1 patient. The mean operative time was (308.13±30.39) min, mechanical ventilation time was (15.42±7.42) h, ICU stay was (46.08±27.32) h, and postoperative hospital stay was (11.71±1.90) d. There were no in-hospital deaths. Postoperative complications included one patient of acute renal failure and one patient of cerebral infarction. Pre-discharge color Doppler echocardiography revealed that the left ventricular end-diastolic diameter was significantly smaller than before surgery (P<0.05), while the left ventricular ejection fraction and fractional shortening were significantly higher (P<0.05). Coronary computed tomography angiography (CTA) showed that all arterial grafts were patent. During a mean follow-up of (14.58±8.75) months, no patients experienced angina recurrence or mortality. Repeat coronary CTA or angiography in 16 patients one year postoperatively confirmed that all arterial grafts remained patent. Conclusion Total arterial OPCABG using a LITA and bilateral RAs is a safe and effective treatment for patients with severe multi-vessel coronary artery disease. For high-risk patients, intraoperative IABP support is recommended.

Objective·To compare the safety and short-term outcomes of robot-assisted versus laparoscopic-assisted proximal gastrectomy combined with double-flap esophagogastrostomy in the treatment of early upper gastric cancer.Methods·A retrospective cohort study was conducted to analyze the clinical and pathological data of 31 early gastric cancer patients who underwent proximal gastrectomy combined with double-flap esophagogastrostomy for gastrointestinal reconstruction at the Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,from September 2023 to March 2024.Based on the surgical approach,patients were divided into the robot-assisted surgery group(robotic group,20 cases)and the laparoscope-assisted surgery group(laparoscopic group,11 cases).General clinical data,intraoperative conditions,and postoperative recovery between the two groups were compared.At the 6-month postoperative follow-up,upper gastrointestinal radiography and esophagogastroscopy were performed to assess anastomotic stricture and gastroesophageal reflux disease.Additionally,the gastric cancer-specific module of the European Organization for Research and Treatment of Cancer(EORTC),Quality of Life Questionnaire-Stomach 22(QLQ-STO22),was used to evaluate the patients' quality of life.Results·The general data of the two groups,including gender,age,preoperative comorbidities,American Society of Anesthesiologists(ASA)classification,Siewert classification,and pathological staging of tumors,showed no statistically significant differences(all P>0.05).All patients successfully underwent the procedure without conversion to open surgery.The time for gastroesophageal anastomosis was significantly shorter in the robotic group compared to the laparoscopic group[(31.09±8.23)min vs(43.73±8.83)min,P<0.001],while there were no statistically significant differences in other intraoperative and postoperative parameters,including operative time,intraoperative blood loss,number of lymph nodes removed,duration of gastric tube placement,time to start a liquid diet,length of postoperative hospital stay,and incidence of postoperative complications(all P>0.05).At the 6-month postoperative follow-up,30 patients completed the follow-up,with one patient lost to follow-up in the robotic group.Upper gastrointestinal radiography and esophagogastroscopy results showed that only one patient in the laparoscopic group developed an anastomotic stricture,while one patient in the robotic group developed grade A and one developed grade B gastroesophageal reflux disease(GERD).In addition,one patient in the laparoscopic group also developed grade B GERD.The incidences of GERD and anastomotic stricture showed no statistically significant differences between the two groups(both P>0.05).EORTC QLQ-STO22 results indicated that the robotic group had significantly lower scores in the dimensions of dysphagia,gastroesophageal reflux,and dietary restrictions,as well as in the total score,compared to the laparoscopic group(all P<0.05).Conclusion·Robot-assisted proximal gastrectomy combined with double-flap esophagogastrostomy is safe and feasible.It shortens anastomosis time and offers potential advantages in postoperative functional recovery and quality of life improvement.

Patients with advanced pregnancy complicated by acute ST-segment elevation myocardial infarction are relatively rare both domestically and internationally,and there are currently no relevant guidelines to guide clinical treatment.In this case,a 39-year-old pregnant woman was admitted to the hospital with sudden chest pain,and the electrocardiogram showed extensive anterior ST-segment elevation myocardial infarction.Coronary angiography showed subtotal subtotal occlusion of the proximal left anterior descending artery.Reperfusion and revascularization were given,and the blood flow grade of the trial of thrombolytic in myocardial infarction was restored.Complete intravascular ultrasonography to determine the cause of occlusion due to spontaneous hematoma of the left anterior descending artery.After the operation,a reasonable antiplatelet and anticoagulant treatment regimen was selected according to the coronary artery lesion,and the pregnancy was terminated at the appropriate time,and 1 live male baby was successfully delivered.Maternal and fetal health was followed up after 1、3 and 6 months.Through the experience and summary of the treatment process,combined with the literature,the pathogenesis of this disease is discussed,and the strategy of revascularization,the selection of antithrombotic drugs and the timing of pregnancy termination are discussed in depth for clinical reference.