ObjectiveTo investigate the expression of scaffold protein PDLIM5 in multiple sclerosis （MS） patients and the mouse microglial cell line BV2， and to explore its effects on the phagocytosis of microglial cells. MethodsPeripheral blood samples were collected from 24 MS patients and 6 healthy volunteers as controls. The expression levels of PDLIM5 were detected by real-time quantitative PCR. A neuroinflammation cell model was established by treating the mouse microglial cell line BV2 with lipopolysaccharide （LPS， 1 µg/mL）. The expression levels of PDLIM5 were measured by Western Blot. The effect of PDLIM5 expression on phagocytosis was analyzed by transfecting BV2 cells with PDLIM5 shRNA plasmids or PDLIM5 overexpression plasmids. ResultsReal-time quantitative PCR results showed that compared with the healthy control group， the expression level of PDLIM5 from the MS patients was significantly increased in monocytes ［2.78 （0.70-6.86） vs. 0.54 （0.39-1.51）， P=0.036］ and lymphocytes ［1.62 （0.90-2.26） vs. 0.11 （0.05-0.21）， P<0.001］. Western Blot results indicated that PDLIM5 expression was significantly upregulated in BV2 cells following LPS stimulation （P<0.05）. Plasmid transfection experiments demonstrated that knockdown of PDLIM5 inhibited the phagocytic capacity of BV2 cells as measured by trypan blue uptake （P<0.05）， while overexpression of PDLIM5 enhanced the phagocytic ability of BV2 cells （P<0.001）. ConclusionUnder neuroinflammatory conditions， PDLIM5 expression is elevated， and this upregulation promotes the phagocytosis of microglial cell.

Objective:To explore the effects of body mass index (BMI) on the incidence of nocturnal hypertension in patients with hypertension.Methods:Totally 341 hospitalized hypertensive patients treated at the Affiliated Hospital of Jining Medical University from February to May 2023 were selected by convenience sampling. Patients' general information, clinical data, and 24-hour ambulatory blood pressure results were collected. A binomial Logistic regression analysis was conducted to investigate the factors affecting the occurrence of nocturnal hypertension in these patients. The relationship between BMI and the incidence of nocturnal hypertension was examined using threshold effect tests and smooth curve fitting.Results:The binomial Logistic regression analysis indicated that blood phosphate level was a factor influencing the occurrence of nocturnal hypertension in hypertensive patients ( P<0.05). Smooth curve fitting and threshold effect test results showed that the relationship between BMI and the incidence of nocturnal hypertension was curve-correlated, with a turning point at 24.61 kg/m 2. To the left of the turning point, there was no correlation ( P=0.130) ; to the right, there was a correlation ( P=0.016) . Conclusions:When the BMI of hypertensive patients exceeds 24.61 kg/m 2, the likelihood of nocturnal hypertension increases with rising BMI, providing a precise intervention target for weight management-based patient care in hypertension.

Objective To investigate the 90%effective dose(ED90)of ciprofol combined with alfentanil in inhibiting gastroscopy insertion response in elderly patients.Methods 110 patients were selected to undergo painless gastroscopy examination on a scheduled basis.110 patients were randomly divided into ciprofol group alone(group H,n=57)and ciprofol group combined with alfentanil 5 μg/kg(group A,n=53).The trial was conducted according to the Biased coin design up-and-down(BCD-UDM)sequential.Patients in group H were given only intravenous infusion of ciprofol and patients in group A were pre-infused with intravenous alfentanil at 5μg/kg,followed by intravenous infusion of ciprofol,and gastroscopy was initiated when the modified observer's assessment of alertness/sedation scale(MOAA/S)was≤1 point.The initial dose of ciprofol was 0.200 mg/kg in all cases,and the adjacent isotropic dose was 0.030 mg/kg.If the patient's MOAA/S was still>1 or the patient had a response that interfered with the operative examination,such as choking or body movement,during gastroscopy placement,2.0 min after the intravenous infusion of ciprofol,was regarded as an ineffective response,then the next patient was elevated by one dose gradient.If the anesthetic effect of the previous patient was judged to be a valid response,the next patient was randomized to a dose according to the BCD-UDM,with an 11%(b=0.11)probability of decreasing the dose gradient by one dose,and an 89%(1-b=0.89)probability of remaining unchanged,and the experiment was terminated at the 45th effective response in each group.Probabilistic unit regression analysis was used to calculate the ED90,95%effective dose(ED95),and 95%confidence intervals(CI)for the inhibition of gastroscopy placement response with ciprofol alone and the combination of 5 μg/kg alfentanil in elderly patients.Results The ED90 of ciprofol in group A was 0.296 mg/kg(95%CI:0.275～0.338),and ED95 was 0.310 mg/kg(95%CI:0.291～0.383);The ED90 of ciprofol in group H was 0.407 mg/kg(95%CI:0.390～0.447),and ED95 was 0.420 mg/kg(95%CI:0.402～0.483).Compared with group H,the total amount of ciprofol was significantly reduced in group A,the time of awakening and time of leaving the hospital were significantly shorter,and the incidence of intraoperative hypotension and hypoxemia was significantly lower,the differences were statistically significant(P<0.05).Conclusion The ED90 of ciprofol combined with 5 μg/kg of alfentanil and ciprofol alone in inhibiting gastroscopy implantation in elderly patients are 0.296 mg/kg and 0.407 mg/kg respectively.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective:To explore the distribution and characteristics of microbiota in the lower reproductive tract of patients with cervical squamous cell carcinoma infected by human papilloma virus (HPV) 16 subtype.Methods:A prospective, cross-sectional study was conducted. A total of 6 patients with HPV16 single subtype positive cervical squamous cell carcinoma admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from August 2019 to June 2020 were selected as cervical carcinoma group, and 6 healthy women who did not indicate abnormalities in thin-based layer cytology test (TCT) during the same period among the physical examination population and had HPV negative test result were selected as the healthy control group. A sterile cotton swab was used to collect secretions from the posterior cervical fornix in patients before antitumor treatment and healthy controls during physical examination. The high variable region of the 16S rRNA gene V1-V2 of the bacteria was amplified by using next generation sequencing (NGS), and then the distribution and characteristics of the bacteria were analyzed.Results:The age of cervical cancer group and the healthy control group was (51±8) years and (48±3) years, respectively, and the difference in age between the both groups was statistically significant ( t= 0.63, P= 0.540). The patients of both groups had reproductive history and no smoking experience. Alpha diversity analysis showed that compared with the healthy control group, the sobs ( t= 3.25, P= 0.009) and chao ( t= 2.91, P= 0.016) indexes were higher in cervical cancer group, and the differences were statistically significant. The shannon index was higher ( t= 2.07, P= 0.065) and simpson index was lower ( t= 1.74, P= 0.113) in cervical cancer group, while the difference was not statistically different. Data dimensionality reduction analysis in principal coordinate analysis (PCoA) based on bray-curtis distance showed that the difference in Beta diversity between the healthy control group and cervical cancer group was statistically significant ( R2= 0.154, P = 0.018). At the phylum level, the proportion of Firmicutes in cervical cancer group was lower than that in the healthy control group (30.21% vs. 68.28%), while the proportion of Bacteroidetes in cervical cancer group decreased slightly (6.87% vs. 8.11%); and the proportion of Actinobacteria (26.91% vs. 14.42%) and Proteobacteria (27.33% vs. 0.67%) had an increase in cervical cancer group. At the genus level, compared with the healthy control group, the proportion of Lactobacillus and Corynebacterium decreased in cervical cancer group, and loss of dominant flora could be detected; while Rhodococcus, Klebsiella and Aerococcus increased significantly in cervical cancer group. The bacteria species in cervical cancer group was increased compared with the healthy control group. Linear discriminant analysis (LDA) showed that Rhodococcus (LDA = 5.04), Klebsiella (LDA = 4.71), Enterobacter (LDA = 4.29), Ralstonia (LDA = 4.28), Ochrobactrum (LDA = 4.23) and Veillonella (LDA = 4.14) were the distinctive microbiota of cervical cancer group at the genus level. At the phylum level, Firmicutes (LDA = 5.23) in the healthy control group could be considered as a marker species. At the species level, the proportions of Rhodococcus ( P = 0.025), Ralstonia ( P = 0.045), Veillonella ( P = 0.044), Paraburkholderia ( P = 0.045), Pseudomonas ( P = 0.043) in cervical cancer group were increased compared with the healthy control group, and the differences were statistically significant. Conclusions:HPV16 single positive patients with cervical squamous cell carcinoma show the characteristics such as the increased diversity and richness of the lower reproductive tract microbiota compared with the healthy controls, while the abundance of Lactobacillus decreases. Rhodococcus and Klebsiella could serve as symbolic microbial in the lower reproductive tract. However, further studies still need to be verified.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Objective To observe the effects of needle-knife tendon-sparing and knot-dissolving technique on NF-κB/Bcl-2 pathway activity and the expression of TNF-α,IL-1β,IL-6,Bax and caspase-3 in synovial tissue of knee joints of rabbits with rheumatoid arthritis(RA)model;To explore the mechanism of its inhibitory effect on RA synovial inflammation.Methods Totally 24 New Zealand white rabbits were randomly divided into normal group,model group,drug group and needle-knife group,with 6 rabbits in each group.Except for the normal group,the other groups were injected with ovalbumin and Freund's complete adjuvant into the knee joint cavity to replicate the RA model,and corresponding interventions were given for 18 consecutive days.The knee pain threshold and knee circumference were measured,ultrasound was used to observe the joint cavity effusion,synovial thickness and internal blood flow signals,the synovial tissue morphology were observed by HE staining,the apoptosis of fibroblast-like synoviocytes(FLS)in synovial tissue was observed by TUNEL staining,the expression of TNF-α,IL-1β and IL-6 in synovial tissue were detected by immunohistochemistry,RT-PCR was used to detect NF-κBp65 and Bcl-2 mRNA expression in synovial tissue,Western blot was used to detect the protein expression of NF-κBp65,p-NF-κBp65,Bcl-2,Bax and caspase-3 in synovial tissue.Results Compared with the normal group,the knee pain threshold decreased,knee circumference increased,ultrasonic score and pathological score of synovial tissue increased in the model group;FLS apoptosis rate decreased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue increased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein increased,while the expression of Bax,caspase-3 protein decreased,with statistical significance(P<0.05).Compared with the model group,the knee pain threshold increased in the drug group and the needle knife group,the circumference of the knee joint decreased,the ultrasonic score and pathological score of synovial tissue were significantly decreased;the apoptosis rate of FLS increased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue decreased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein decreased,and the expression of Bax and caspase-3 protein increased,with statistical significance(P<0.05).Conclusion Needle-knife tendon-sparing and knot-dissolving technique may promote FLS apoptosis and reduce TNF-α,IL-1β and IL-6 production,inhibit synovial inflammation in RA,reduce knee joint swelling,and raise pain threshold by reducing the activity of synovial tissue NF-κB/Bcl-2 pathway.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.