ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

Aim To explore the therapeutic effect of Qingjie Huagong decoction in regulating RIPK1/RIPK3/MLKL signaling pathway on pancreatic necrotic apoptosis in rats with severe acute pancreatitis(SAP)and the underlying mechanism.Methods The SAP rat model was established by retrograde pancreaticobili-ary injection of sodium taurocholate,and the sham-op-eration group,the model group,the group with differ-ent dosages of Qingjie Huagong decoction and the posi-tive control group were set up respectively.The group with different dosages of Qingjie Huagong decoction was given low,medium and high dosages of traditional Chinese medicine in the gastric gavage,the positive control group was given ulinastatin drug intervention,and the sham-operation and the model group were giv-en physiological saline in the gastric gavage;HE stai-ning was applied to observe pancreatic pathology;ELISA was used to measure the serum levels of α-am-ylase,IL-1β,IL-6,and TNF-α;immunohistochemis-try and Western blot were employed to determine the RIPK1,RIPK3,MLKL protein expression in rat pan-creatic tissue;and qRT-PCR was utilized to detect the transcription levels of R1PK1,RIPK3 and MLKL mR-NA in rat pancreatic tissue.Results Compared with the sham-operated group,the model group showed dif-fuse necrosis of pancreatic acinar cells,obvious inter-lobular septal edema,inflammatory cell infiltration,significantly higher levels of α-amylase,IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher ex-pression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P＜0.01)in the model group;com-pared with the model group,the Qingjie Huagong de-coction dose groups and positive control group signifi-cantly improved pancreatic histopathology,reduced pancreatic tissue necrosis and apoptosis,lowered the expression levels of α-amylase,IL-1 β,IL-6 and TNF-α(P＜0.01),and reduced the expression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P＜0.01).Conclusions Qingjie Huagong decoction may improve the necrotic apoptosis of pancreatic tissue by regulating the RIPK1/RIPK3/MLKL signaling path-way,thus playing a role in protecting pancreatic tissue and slowing down the progression of the disease.

Aim To investigate the therapeutic effect of luteolin(LUT)on myasthenia gravis(MG)rats and its mechanism.Methods Female Lewis rats were di-vided into five groups:C group,MG group,low dose luteolin group(L-LUT),medium dose luteolin group(M-LUT)and high dose luteolin group(H-LUT),with 12 rats in each group.Rats in C group were nor-mal control rats.Rats in other groups were MG model rats induced by subcutaneous injection of Rα97-116.Rats in C group and MG group were intragastrically fed with 1 mL corn oil.Rats in L-LUT group,M-LUT group and H-LUT group were intragastrically infused with 1 mL 10,20 and 40 mg·kg-1 luteolin solution,respectively.The administration period was four weeks.Lennon grading method was used to score clini-cal symptoms,and EMG evoked potential instrument was used to detect the attenuation rate of low frequency repetitive nerve stimulation(RNS).The morphology of skeletal muscle was observed by hematoxylin eosin(HE)staining.The levels of serum AChR antibody(AChR-Ab),interferon gamma(IFN-γ)and interleu-kin-4(IL-4)were detected by ELISA method.The activity of superoxide dismutase(SOD)in skeletal muscle was detected by visible spectrophotometry,and glutathione peroxidase(GSH-Px)and malondialde-hyde(MDA)were detected by micromethod.The mR-NA levels of peroxisome proliferator-activated receptorγ coactivator-1α(PGC-1α),nuclear respiratory factor 1(NRF1)and mitochondrial transcription factor A(TFAM)in skeletal muscle were measured by qRT-PCR.The protein expression levels of AMP-activated protein kinase α(AMPKα)and p-AMPKα in skeletal muscle were detected by Western blot.Results Com-pared with C group,Lennon score and RNS decay rate in MG group increased,AChR-Ab and IFN-γ levels increased,skeletal muscle showed obvious injury,SOD and GSH-Px levels decreased,MDA levels in-creased,p-AMPKα protein expression levels and PGC-1α,NRF1 and TFAM mRNA levels decreased(P＜0.05).Compared with MG group,Lennon score and RNS decay rate in L-LUT group and M-LUT group M and H-LUT group decreased,AChR-Ab and IFN-γlevels decreased,skeletal muscle damage was allevia-ted,SOD and GSH-Px levels increased,MDA levels decreased,p-AMPKα protein expression levels and PGC-1α,NRF1 and TFAM mRNA levels increased(P＜0.05).Conclusion The mechanism of luteolin in treating MG rats may be related to correcting the bal-ance of Th1/Th2 cells and activating AMPK.

Objective To explore the safety and effectiveness of the robot-assisted system for transforaminal percutaneous endoscopic in the treatment of lumbar disc herniation with lumbar instability.Methods From October 2021 to March 2023,26 patients with single-segment lumbar disc herniation and lumbar spinal instability were treated with robot-assisted system for transforaminal percutaneous endoscopic.The operation time,intraoperative blood loss,incision length,postoperative drainage volume,postoperative ambulation activity time,postoperative hospitalization time were record.The intervertebral space height and the lumbar lordosis angle before and after surgery were observed and compared.Pain level was evaluated using the visual analogue scale(VAS).The clinical efficacy was evaluated by Oswestry disability index(ODI).The interbody fusion was evalu-ated by Brantigan Steffee criteria.Results All patients successfully completed the operation,the operation time ranged form 105 to 109 min with an average of(150.8±24.1)min.Intraoperative blood loss ranged form 35 to 88 ml with an average of(55.5±16.4)ml.Incision length ranged form 1.4 to 3.5 cm with an average of(2.3±0.8)cm.Postoperative drainage volume ranged form 15 to 40 ml with an average of(28.5±7.8)ml.Postoperative ambulation time ranged form 15 to 30 h with an aver-age of(22.8±4.5)h.Postoperative hospitalization time was 3 to 7 d with an average of(4.2±1.3)d.Total of 26 patients were followed up,the duration ranged from 12 to 16 months with an average of(14.0±1.3)months.The VAS and ODI at 1 week[(2.96±0.72)points,(41.63±4.79)％]and 12 months[(1.27±0.60)points,(13.11±2.45)％]were significantly different from those before surgery[(6.69±0.93)points,(59.12±5.92)％],P＜0.0 1.The height of the intervertebral space(11.95±1.47)mm and lumbar lordosis(57.46±7.59)° at 12 months were significantly different from those before surgery[(6.67±1.20)mm,(44.08±7.79)°],P＜0.01.At 12 months after surgery,all patients had no pedicle screw rupture or dislocation of the fusion cage,and the intervertebral fusion was successful.According to Brantigan-Steffee classification,17 cases were grade D and 9 cases were grade E.Conclusion Robot-assisted system for transforaminal percutaneous endoscopic for the treatment of single-segment lumbar disc herniation with lumbar instability improved the accuracy and safety of the operation,and the clinical effect of early follow-up is accurate.

Objective To investigate the efficacy of different approaches for screw internal fixation in the treatment of posterior ankle fractures in trimalleolar fracture,and the complications was analyzed.Methods A prospective study was conducted on 80 patients with Haraguchi type Ⅰ posterior ankle fracture who admitted to our hospital from May 2019 to October 2020,they were randomly divided into group A and group B according to a random number table method,with 40 cases in each group.Patients in group A were treated with percutaneous anterior to posterior screw internal fixation for posterior ankle fractures,while patients in group B were treated with percutaneous posterolateral approach limited exposure and reduction screw internal fixation for posterior ankle fractures.The surgical indicators,postoperative recovery,American Orthopaedic Foot and Ankle Society(AOFAS)score,ROM score of ankle joint at the last follow-up,postoperative evaluation,and postoperative complications of patients between the two groups were compared.Results There was no statistically significant difference in operation time,complete weight-bearing time,or fracture healing time of patients between the two groups(P>0.05),but the fluoroscopy times of patients in group A was less than that in group B,the intraoperative bleeding volume and fibular incision length were less/shorter than those in group B(P<0.05).The AOFAS scores of patients 6 months after surgery and at the last follow-up in both groups increased compared with those 3 months after surgery,and the AOFAS scores at the last follow-up were higher than those 6 months after surgery,the differences were statistically significant(P<0.05).The AOFAS scores of patients 6 months after surgery and at the last follow-up in group B were higher than those in group A(P<0.05).There was no statistically significant difference in ROM score of ankle joints(plantar flexion,valgus,varus,dorsiflexion)of patients between the two groups at the last follow-up(P>0.05).There was no statistically significant difference in poor screw position,degree of pain,walking condition,or squatting condition of patients between the two groups(P>0.05).However,the reduction quality of posterior ankle fractures of patients in group B was better than that in group A(Z=4.248,P<0.05).No complications such as loosening of internal fixation or loss of fracture reduction occurred in both groups.Conclusion Both percutaneous anterior to posterior screw internal fixation and percutaneous posterolateral approach limited exposure and reduction screw internal fixation have good efficacy for posterior ankle fractures in trimalleolar fracture,with high safty.The former has more fluoroscopy times and less intraoperative bleeding,while the latter is better in improving ankle joint function and fracture reduction.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Objective:To evaluate the effect of low-dose esketamine for postoperative analgesia on the postoperative depression in patients with gastrointestinal tumors.Methods:This study was a prospective randomized controlled trial. Eighty patients, aged 18-64 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection of the gastrointestinal tumor under general anesthesia from June to November 2023 in our hospital, were divided into 2 groups ( n=40 each) using a random number table method: esketamine group (group E) and control group (group C). Each patient received postoperative patient-controlled intravenous analgesia(PCIA). The PCIA solution in group E contained esketamine 0.5 mg/kg, dezocine 0.5 mg/kg, dexmetomidine 1.5 μg/kg and flurbiprofen ester 100 mg in 100 ml of normal saline. The PCIA solution in group C contained dezocine 0.5 mg/kg, dexmetomidine 1.5 μg/kg and flurbiprofen ester 100 mg in 100 ml of normal saline. The Hospital Anxiety and Depression Scale (HADS) was used to assess the patients′ anxiety and depression at 1 day before operation (T 0) and 2 days after operation (T 1). The Quality of Recovery-15 scale was used to evaluate the early postoperative recovery quality. Visual analog scale scores, the pressing times of patient-controlled analgesia and the number of rescue analgesia were recorded within 2 days after operation. The occurrence of drug-related adverse reactions was also recorded. Results:Seventy-eight patients were finally included, with 39 cases in group E and 39 cases in group C. Compared with group C, the postoperative HADS-depression scale score and incidence of depression were significantly decreased, the Quality of Recovery-15 scale score was increased, the visual analog scale scores were decreased ( P<0.05), and no significant changes were found in the postoperative HADS-anxiety scale score and incidence of anxiety, the pressing times of patient-controlled analgesia and the number of rescue analgesia in group E ( P>0.05). Visual hallucination was found at 1 day after operation in one patient and relieved at 2 days after operation in group E. There was no significant difference in the incidence of postoperative dizziness, nausea and vomiting between the two groups ( P>0.05). Conclusions:Postoperative analgesia with 0.5 mg/kg esketamine can alleviate postoperative depressive symptoms, enhance the efficacy of analgesia and improve the early postoperative recovery quality in patients with gastrointestinal tumors.

Objective:To evaluate the efficacy of remimazolam for induction of anesthesia in patients with colorectal cancer.Methods:This was a prospective study. Eighty-two patients scheduled for elective colon and rectal tumor surgery under general anesthesia from June to November 2023 at our hospital, aged 18-80 yr, with body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, were divided into 2 groups ( n=41 each) using a random number table method: propofol group (group P) and remimazolam group (group R). Propofol 1.5 mg/kg was intravenously injected in group R and remimazolam 0.3 mg/kg was intravenously injected in group P. When the bispectral index (BIS) value≤60, sufentanil 0.5 μg/kg and cisatracurium 0.2 mg/kg were intravenously injected in both groups. Heart rate and mean arterial pressure were recorded before induction of anesthesia (T 0), 3 min after induction (T 1), immediately after intubation (T 2), and 5 min after tracheal intubation (T 3). The occurrence of hypotension, hypertension, tachycardia and bradycardia during induction, use of vasoactive drugs, and injection pain were recorded. The time to loss of consciousness, time from the beginning of administration to BIS value ≤60, time from the beginning of administration to tracheal intubation, occurrence of BIS value > 60 immediately after intubation and rescue sedation were recorded. Results:Eighty patients were finally included, with 40 in group P and 40 in group R. Compared with group P, the heart rate and mean arterial pressure were significantly increased at T 1 and T 2, the incidence of hypotension and bradycardia was decreased, and the time from the beginning of administration to BIS value ≤60 was prolonged ( P<0.05), and no statistically significant changes were found in the other parameters in group R ( P>0.05). Conclusions:Remimazolam 0.3 mg/kg can be safely and effectively used for anesthesia induction and provides better efficacy in maintaining hemodynamic stability when compared with propofol 1.5 mg/kg in patients with colorectal cancer.

AIM To investigate the protective effect of Mongolian medicine Naru-3 on rat rheumatoid arthritis(RA)using imaging method.METHODS With the rats divided into the normal group,the model group,the positive medicine group,and the low,medium and high dose Naru-3 groups(0.1,0.2 and 0.4 g/kg),the rat model of collagen-induced arthritis(CIA)was established by immune induction method.After 4 weeks of corresponding drug administration,the rats had their changes of arthritis index(AI)level and body weight observed;their serum levels of VEGF,TNF-α and IL-1 detected by ELISA;their synovial hyperplasia and neovascularization evaluated by high-frequency ultrasound and contrast-enhanced ultrasound(CEUS);their bone destruction of ankle joint evaluated by X-ray and high-resolution micro-CT;and their synovial membrane and expressions of CD31,VEGF,TNF-α and IL-1 β observed by HE and immunohistochemistry.RESULTS Compared with the model group,the Naru-3 groups displayed increased rat weight(P＜0.05);no significantly changed AI score(P＞0.05);and overally decreased levels of serum VEGF,TNF-α,synovial membrane thickness,blood flow signal by power Doppler imaging(PDI)and contrast intensity revealed,X-ray score,and CD31 expression(P＜0.05),in addition to the decreased level of IL-1 and HE score in high-dose group(P＜0.05).CONCLUSION Naru-3 is protective to the joint tissue in rat model of RA through alleviating synovitis,bone erosion and delaying the progress of the disease by inhibiting synovial neovascularization and inflammatory cytokines.