OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

Myasthenia gravis is an autoimmune disorder characterized by impaired neuromuscular transmission. Thymectomy is one of the therapeutic options for acetylcholine receptor antibody-positive myasthenia gravis patients. The quality of perioperative care is directly associated with surgical safety and patient outcomes. However, there is currently a lack of specialized nursing consensus or guidelines specifically addressing the care of these patients domestically or internationally. To promote the standardization and normalization of perioperative nursing care for myasthenia gravis patients undergoing thymectomy and to ensure treatment efficacy, a panel of 57 experts from relevant fields was convened. Based on evidence-based medicine and clinical practice experience, discussions were held on various aspects including condition assessment, nutritional support, medication management, and airway care, resulting in a consensus with 18 final recommendations by using the Delphi method through two rounds of expert consultation. This consensus aims to provide a scientific reference for the perioperative nursing care of myasthenia gravis patients undergoing thymectomy.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

ObjectiveThe aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM. MethodsA total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20-25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6. ResultsTwelve hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins. ConclusionA 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.

Objective To evaluate the resuscitation efficacy of novel lyophilized platelets(LP,thrombin-stimulated platelets)combined with lactated Ringer's(LR)solution in rabbits with hemorrhagic shock and seawater immersion.Methods Fifty rabbits were randomly assigned to 5 groups(Groups A,B,C,D and E,n=10).After all rabbits were anesthetized with 3%pentobarbital sodium at a dose of 1 mL/kg,soft tissue injury was inflicted in the left lower limb.The blood loss from the soft tissue injury was quantified after gauze hemostasis.The right lower limb was subjected to femoral artery catheterization,followed by blood withdrawal equivalent to 26%of the total blood volume of the rabbit.The rabbits were then vertically immersed in 3%artificial seawater,with the water level reaching above the xiphoid process,and were retrieved in 15 min later.Resuscitation strategies were applied to the rabbits from different group:Group A(no resuscitation),Group B(resuscitation with LR solution),Group C(resuscitation with LR solution and fresh platelets),Group D(resuscitation with LR solution and LP),and Group E(resuscitation with LR solution and novel LP).Coagulation function test,routine blood test,blood gas analysis,and thromboelastography were conducted at baseline and at 1,2 and 4 h after injury.Results The LP and rabbit model of hemorrhagic shock and seawater immersion were successfully prepared.At 1 h after injury,the mean arterial pressure(MAP)of Groups C,D and E(infused with platelet preparations)was significantly higher than that of Group A(without resuscitation,P<0.05);the lactate(Lac)content of Group C was obviously lower than that of Groups A and B(P<0.05);the base excess(BE)and blood urea nitrogen(BUN)levels of Groups C,D and E were notably lower than those of Groups A and B(P<0.05);and the prothrombin time(PT)of Group A was significantly longer than that of before injury(P<0.05).At 2 h after injury,the MAP of Groups C and D was significantly higher than that of Groups A and B,and that of Group E was notably higher than that of Group A(P<0.05);the Lac content of Groups C and E was obviously lower than that of Groups A and B,while that of Group D was also lower than that of Group A(P<0.05);the BE and BUN levels of Groups C,D and E were remarkably lower than those of Groups A and B(P<0.05);the maximum amplitude(MA)value of Group C was higher than that of Group A,while the value of Groups A and D at this time was significantly lower than the corresponding value before injury(P<0.05);and the activated partial clotting time(APTT)of Groups A and D was statistically longer than the corresponding baseline time(P<0.05).At 4 h after injury,the MAP of Groups C,D,and E was higher than that of Groups A and B,and that of Group B was higher than that of Group A(P<0.05);the Lac and BUN levels of Groups C,D,and E were lower than those of Groups A and B(P<0.05);the BE level of Groups C and D were lower than those of Groups A and B(P<0.05);the MA value of Groups B,C,and E were higher than those of Group A(P<0.05),while the MA value and APTT value of Groups A and D were significantly lower than their corresponding baseline values(P<0.05).Conclusion For rabbits with hemorrhagic shock and seawater immersion,the novel LP combined with LR solution can significantly increase the MAP level,reduce Lac content,and sustainably maintain blood clot firmness and coagulation function.

Peripheral vascular intervention involves multi-site and complex vascular lesions.The construction of a realistic model and the implementation of surgical simulation with the help of simulation medical technology can be applied to the training of interventional physicians and the optimization of individualized treatment strategies for patients.In order to adapt to the simulation scenarios of different blood vessels and achieve the required simulation effects,there have already been many reports concerning the construction of peripheral vascular models and clinical applications,such as the construction of animal models and cadaver models,the application of virtual reality simulators,the construction of different types of 3D printing vascular models,etc.This paper aims to make a detailed review about the methods of constructing these models and the research progress in the individualized diagnosis and treatment of patients.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Objective:To investigate the clinical characteristics and prognosis of follicular lymphoma (FL) patients with different primary sites using the Surveillance, Epidemiology, and End Results (SEER) database.Methods:Clinical data of 7167 patients with early-stage FL (stage I-II) from the SEER database between 2000 and 2015 were respectively analyzed. Primary sites were divided into intranodal and extranodal types. Intranodal primary sites included supradiaphragmatic lymph nodes (LN), subphrenic lymph nodes and Waldeyer's ring. Extranodal primary sites consisted of skin, gastrointestinal tract, duodenum, head and neck, other sites. Prognostic factors and overall survival (OS) in patients with different primary sites were analyzed. OS rate was evaluated using Kaplan-Meier method and survival difference between primary sites was compared with log-rank test. Inverse probability treatment weighting (IPTW) and multi-variable analysis were applied to adjust for confounding factors. Multivariate Cox regression analysis of influencing factors of OS was performed.Results:The median age was 63 years old, with the median follow-up time of 63 months. There was no difference in prognosis among the intranodal groups or between the intranodal and extranodal groups. The 10-year OS rates of the supradiaphragmatic lymph LN ( n=2146), subdiaphragmatic LN ( n=2811), and the Waldeyer's ring ( n=151) groups were 70.7%, 69.9% and 73.4%, respectively ( P=0.422 for infradiaphragmatic LN vs. supradiaphragmatic LN, P=1.000 for Waldeyer's ring vs. supradiaphragmatic LN), and 70.3% and 68.9% for intranodal ( n=5108) and extranodal ( n=2059), respectively. There was no significant difference in OS between the groups ( P=0.581) after IPTW adjustment. The most common primary sites in extranodal disease were skin, gastrointestinal tract, head and neck, and duodenum. The 10-year OS for skin, gastrointestinal tract, and cutaneous was 74.2%, 74.7%, and 87.3%, respectively, significantly higher than 55.6% for other sites (duodenum vs. others sites, gastrointestinal vs. others sites, skin vs. others sites: all P<0.001). Multivariate Cox regression analysis revealed that difference in OS was not significant among the intranodal groups or between the intranodal and extranodal groups. However, different extranodal primary site was an independent prognostic factor for OS. Conclusions:Early FL patients with supradiaphragmatic LN, subdiaphragmatic LN and Waldeyer's ring, and between the intranodal and extranodal primary sites obtain similar prognosis. However, early-stage FL patients with different extranodal primary sites have prognostic differences. The prognosis of primary skin, gastrointestinal tract and duodenum is significantly better than that of other extranodal primary sites.