PURPOSE: Traumatic brain injury (TBI) is a significant public health issue that impacts individuals all over the world and is one of the main causes of mortality and morbidity. Decompressive craniectomy is the usual course of treatment. Basal cisternostomy has been shown to be highly effective as an alternative procedure to decompressive craniectomy. METHODS: We conducted a retrospective cohort of patients who received surgery for severe TBI between January 2019 and March 2023. Inclusion criterias were patients between the ages of 18 and 70 years who met the diagnostic criteria for severe TBI at first presentation and who underwent surgical intervention. The exclusion criteria were patients who have severe multiple injuries at the time of admission; preoperative intracranial pressure > 60 mmHg; cognitive impairment before the onset of the disease; hematologic disorders; or impaired functioning of the heart, liver, kidneys, or other visceral organs. Depending on the surgical approach, the patients were categorized into decompressive craniectomy group as well as basal cisternostomy group. General data and postoperative indicators, including Glasgow coma scale, intracranial pressure, etc., were recorded for both groups of patients. Among them, the Glasgow outcome scale extended assessment at 6 months served as the primary outcome. After that, the data were statistically analyzed using SPSS software. RESULTS: The trial enrolled 41 patients (32 men and 9 women) who met the inclusion criteria. Among them, 25 patients received decompressive decompressive craniectomy, and 16 patients received basal cisternostomy. Three days postoperative intracranial pressure levels were 10.07 ± 2.94 mmHg and 17.15 ± 14.65 mmHg (p = 0.013), respectively. The 6 months following discharge Glasgow outcome scale extended of patients was 4.73 ± 2.28 and 3.14 ± 2.15 (p = 0.027), respectively. CONCLUSION Our study reveals that basal cisternostomy in patients with surgically treated severe TBI has demonstrated significant efficacy in reducing intracranial pressure as well as patient prognosis follow-up and avoids removal of the bone flap. The efficacy of cisternostomy has to be studied in larger, multi-clinical center randomized trials.
Humans ; Brain Injuries, Traumatic/surgery* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Decompressive Craniectomy/methods* ; Aged ; Young Adult ; Adolescent ; Glasgow Coma Scale ; Treatment Outcome

OBJECTIVES: To characterize the biological properties of double-negative T (DNT) cells isolated from leukoreduction filter residues. METHODS: Leukoreduction filters containing residues from 400 mL whole blood units (n=6) were collected from a blood center. Filters were back-flushed with normal saline, and the eluate was concentrated to obtain leukoreduction filter residues. Leukocytes in the residues were counted by dual-fluorescence staining. DNT cells were then isolated from the residues using antibody-mediated adsorption and density gradient centrifugation. Both cryopreserved and fresh unstimulated DNT cells derived from the residues were subjected to in vitro culture. Following culture, cells were assessed for expansion fold, viability, immunophenotype, differentiation status, and cytotoxicity against target cells using dual-fluorescence staining and flow cytometry, with comparisons made to DNT cells derived from whole blood. RESULTS: The leukocyte recovery rate achieved through reverse flushing of the leukocyte reduction filter was (41.9±14.7)%. Compared to whole blood, the DNT cell starting material obtained from filter residues showed no significant difference in total T-cell content (P>0.05). However, the viability and purity of the resulting DNT cell starting materials were significantly lower (both P<0.05). After 17 days of culture, DNT cells from filter residues and whole blood showed no significant differences in expansion fold, immunophenotype, differentiation status, or cytotoxicity toward target cells (all P>0.05). However, the viability of DNT cells from residues was significantly lower than that of whole blood-derived DNT cells [(86.0±4.2)% vs. (92.2±1.2)%, P<0.05]. After thawing (post 3 or 15 days of cryopreservation) and 17 days of culture, DNT cell starting materials from residues showed comparable immunophenotype, expansion fold, and differentiation status to their non-cryopreserved counterparts from the same source (all P>0.05). However, the viability of DNT cells cryopreserved for 3 days [92.4% (91.8%, 92.8%)] and the cytotoxicity against target cells of those cryopreserved for 15 days [91.3% (89.4%, 95.1%)] were significantly higher than those of non-cryopreserved DNT cells [87.8% (82.0%, 89.0%) and 70.9% (67.3%, 80.2%), respectively] (P<0.05). CONCLUSIONS DNT cells derived from leukoreduction filter residues exhibited highly comparable characteristics to those from whole blood in terms of expansion, purity, differentiation, and biological potency. Furthermore, their biological activity post-cryopreservation and revival remained largely similar to non-cryopreserved cells. These findings suggest that leukoreduction filter residues represent a promising alternative source of starting material for manufacturing off-the-shelf, allogeneic DNT cell therapeutics.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

In order to establish a serological method for the detection of bovine parainfluenza virus type 3(BPIV3),the prokaryotic expression and purification of BPIV3 HN,NP,F,and P proteins were carried out,and the optimal protein-coated antigen was screened,and an indirect ELISA de-tection method was established.The results showed that the four recombinant proteins of BPIV3,rHN,rNP,rF,and rP were expressed,and the checkerboard titration results showed that rHN pro-tein had the highest P/N value as the coating protein,so it was used for the subsequent method es-tablishment.The optimal reaction conditions for indirect ELISA were found to be:the mass con-centration of the antigen coating was 0.5 mg/L,37 ℃ 1.5 h,5％skim milk,overnight blocking at 4 ℃,serum dilution at 1∶50,incubation at 37 ℃ 1 h,secondary antibody dilution at 1∶10 000 and incubation at 37℃ 0.5 h,substrate reaction conditions were 37℃ for 12 min.The results of speci-ficity experiments showed that the established method could specifically identify BPIV3 antibody-positive serum with a sensitivity of 1∶800,and the coefficient of variation in the detection of intra-and inter-assay repeatability was less than 10％,and the overall coincidence rate of the same batch of samples detected with the SVANOVIR kit was 92.22％.This method was used to detect 192 se-rum samples in Hebei Province,and the positive rate of BPIV3 antibody in serum was 66.15％.The indirect ELISA detection method of BP1V3 antibody constructed in this study is suitable for large-scale clinical serological investigations,and provides valuable data support for the research and de-velopment of BPIV3 antigen and antibody detection kits in China.

Objective To explore the characteristics of fluid flow within loaded osteons under different boundary conditions.Methods The COMSOL Multiphysics software was used to establish a three-dimensional(3D)finite element model of osteons with different boundary conditions,and the variation rules of pore pressure and flow velocity of osteons under different inner wall pulsating blood pressures and outer wall elastic constraint conditions were analyzed.Results As the pulsatile blood pressure inside the osteon increased from 0 mmHg(1 mmHg=0.133 kPa)to 300 mmHg,the peak pore pressure within the osteon correspondingly increased from 26 kPa to 68 kPa.As the elastic constraint on the outer wall of osteons changed from being completely elastic to completely constrained,the peak pore pressure within osteons increased from 15 kPa to 26 kPa,and the peak flow velocity increased from 0.04 um/s to 0.07 um/s.Conclusions This study reveals the influence laws of changes in boundary conditions such as the pulsatile blood pressure on the inner wall and the elastic constraint on the outer wall of osteons on fluid flow characteristics within loaded osteons.These findings are conducive to a deeper understanding of the mechanical response mechanisms of bone tissues in both physiological and pathological states,and provide an important theoretical basrs for further researches on bone mechanotransduction.

Objective To investigate the efficacy and safety of Linaclotide combined with Simethicone oil and compound polyethylene glycol electrolyte(PEG)for cleansing effect of bowel in patients with constipation.Methods A prospective randomized controlled trial was designed and implemented by single blind method.383 patients with constipation who underwent colonoscopy from April 2023 to August 2024 were enrolled and randomly divided into routine group(128 cases),experimental group A(128 cases)and experimental group B(127 cases).Routine group treated with 3 L PEG,experimental group A treated with 290 μg Linaclotide+2 L PEG and experimental group B treated with 290 μg Linaclotide+30 mL Simethicone+2 L PEG.Bowel preparation effect[Boston bowel preparation scale(BBPS)scores and foaming removal effect],lesion detection rate,first defecation interval,frequency of defecation,the success rate of cecal intubation,the insertion time of colonoscopy,the withdrawal time of colonoscopy,incidence of adverse reactions and willingness to repeat examination of the three groups were compared.Results No statistically significant differences were observed in the BBPS scores among the three groups(P>0.05);The foaming removal effect score in experimental group B was significantly lower than that in routine group and experimental group A,the difference was statistically significant(P<0.05);The total lesion detection rate and polyps detection rate of experimental group B were significantly higher than those of routine group and experimental group A,the differences were statistically significant(P<0.05).The first defecation interval of the routine group was significantly longer than that of experimental group A and experimental group B,the difference was statistically significant(P<0.05);The frequency of defecation was compared among the three groups,and the difference was no statistically significant(P>0.05).The success rate of cecal intubation in the three groups was 100.0%,and the insertion time of colonoscopy was similar,the differences were not statistically significant(P>0.05);The withdrawal time of colonoscopy in experimental group B was significantly shorter than that in routine group and experimental group A,the difference was statistically significant(P<0.05).The incidence of abdominal distension and total adverse reactions in the routine group were higher than those in experimental group A and experimental group B,the differences were statistically significant(P<0.05);The willingness to repeat examination rate of the routine group was significantly lower than that of experimental group A and experimental group B,the differences were statistically significant(P<0.05).Conclusion 290 μg Linaclotide combined with 30 mL Simethicone and 2 L PEG solution regimen has advantages in intestinal preparation for patients with constipation,and can achieve better intestinal cleaning effect than 3 L PEG solution and 290 μg linalopeptide+2 L PEG solution regimen,with higher safety and willingness to repeat examination.It can be recommended for bowel preparation for patients with constipation.

Objective To investigate the effect of fumigation decoction on the expression of aggrecan(AGG)and type Ⅱ collagen(COL2A1)in an intervertebral disc degeneration(IDD)model,and to gain an in-depth understanding of the cellular and molecular mechanisms underlying traditional Chinese medicine fumigation therapy.Methods An IDD model was established using Sprague-Dawley rats by inducing disc injury via needle puncture.The rats were divided into three groups:normal control(CON),model(PUN),and fumigation(CHF).Only the CHF group received treatment with fumigation decoction for 4 weeks.Imaging analysis was conducted to assess the relative height of intervertebral discs,while Masson's trichrome staining was used to observe structural changes in the discs.The expression of NLRP3 inflammasome was detected by immunohistochemistry.Quantitative RT-PCR and Western blotting were employed to evaluate the expression levels of AGG and COL2A1 genes and proteins.Results A total of 12 rats were randomly divided into 3 groups,with 4 rats in each group.Compared with the CON group,disc height was significantly lost in the PUN group(P＜0.05),and disc height could be partially restored in the CHF group(P＜0.05).In the PUN group,the expression levels of AGG mRNA and COL2A1 mRNA and protein in the nucleus pulposus tissue were significantly lower than those in the CON group(P＜0.05).Compared with the PUN group,the CHF group showed significantly increased expression levels of AGG mRNA and COL2A1 mRNA and protein in the nucleus pulposus tissue(P＜0.05).Histological analysis revealed that,compared with the PUN group,the CHF group exhibited partial restoration of the gel-like properties of the nucleus pulposus and an increase in proteoglycan content.Additionally,NLRP3 expression in the nucleus pulposus tissue of the CHF group was markedly reduced.Conclusion Fumigation decoction treatment can enhance the expression of AGG and COL2A1 and decrease the expression of NLRP3 in IDD models,which may be one of its mechanisms for treating lumbar degenerative diseases.This research provides new insights into the treatment of IDD.

Objectives:To investigate the effect and mechanism of mitochondrial targeting peptide SS-31 on senescence and pyroptosis of nucleus pulposus(NP)cells induced by inflammation.Methods:NP cells were isolated and cultured in vitro from 6-week-old male SD rats,and were divided into control group,lipopolysaccharide(LPS)group,and LPS+SS-31 group;And the control group of cells received no treatment,LPS group of cells were treated with 100μg/mL LPS for 24h,and LPS+SS-31 group of cells were pre-treated with SS-31 30min before LPS intervention.The levels of cellular senescence and pyroptosis were assessed in each group using β-galactosidase(SA-β-Gal)staining and westem blot(WB)assay;Transmission electron mi-croscopy and oxygen consumption rate(OCR)assay were used to analyze the mitochondrial function of NP cells in each group;The expressions of phosphorylated nuclear factor-κB-p65(p-NF-κB-p65),cyclic GMP-AMP synthase(cGAS),and interferon stimulating gene(STING)in each group were detected by WB and im-munofluorescence;Hematoxylin-eosin(HE)staining,immunohistochemistry(IHC)staining and WB assay were performed to analyze the effects of in vivo injection of SS-31 on intervertebral disc degeneration,senescence,and pyroptosis.Results:The positive SA-β-Gal staining of NP cells,expression of senescence marker pro-teins(p53,p21),and pyroptosis-related molecules(NLRP3,Caspase-1 p20)were significantly lower in the LPS+SS-31 group compared with the LPS group(P＜0.05);Transmission electron microscopy(TEM)showed that the mitochondrial swelling of NP cells was round,the matrix was translucent,and the interstitial lumen of the mitochondrial cristae was dilated in the LPS group,while the mitochondrial swelling was subsided,and the morphology of mitochondria tended to be normalized in the LPS+SS-31 group.Meanwhile,the maximum respi-ration level of NP cells was significantly enhanced in the LPS+SS-31 group compared with the LPS group(P＜0.05).The results of WB and immunofluorescence showed that LPS significantly up-regulated the expression of p-NF-κB-p65,cGAS,and STING(P＜0.05),while SS-31 pretreatment significantly inhibited the expression of p-NF-κB-p65,cGAS and STING in NP cells induced by LPS(P＜0.05).Finally,in vivo experiments con-firmed that local injection of SS-31 reduced the senescence and pyroptosis of NP cells,and alleviated the degeneration of intervertebral disc induced by annulus fibropuncture.Conclusions:SS-31 alleviates inflamma-tion-induced senescence and pyroptosis of NP cells,which is related to the inhibition of NF-κB signaling pathway and cGAS/STING signaling pathway.

Objective To investigate the clinical effect of simultaneous use of three endoscopes(laparoscope,choledochoscope,and duodenoscope)combined with holmium laser in the treatment of gallstones complicated with common bile duct stones.Methods A prospective randomized controlled study was carried out.A total of 80 patients with cholecystolithiasis combined with choledocholithiasis in our hospital from August 2022 to January 2024 were selected and divided into three-endoscope group(n=40)and two-endoscope group(n=40)according to random number table method.Patients in the three-endoscope group underwent laparoscopic cholecystectomy(LC)and laparoscopic common bile duct exploration(LCBDE)combined with holmium laser lithotripsy,primary closure of the common bile duct,endoscopic retrograde cholangiopancreatography(ERCP),and endoscopic nasobiliary drainage(ENBD),while the two-endoscope group underwent LC+LCBDE+T-tube drainage.The intraoperative bleeding volume,operation time,hospitalization time,hospitalization costs,and postoperative complications between the two groups were observed and analyzed.Results There was no significant difference in intraoperative bleeding volume between the two groups[(55.6±14.3)ml vs.(53.2±16.3)ml,t=0.703,P=0.484].The operation time of the three-endoscope group was significantly longer than that in the two-endoscope group[214.5(171.5,246.8)min vs.178.0(151.0,227.8)min,Z=-2.069,P=0.039].The length of hospital stay in the three-endoscope group was significantly shorter than that in the two-endoscope group[(13.2±3.3)d vs.(16.2±3.7)d,t=3.864,P=0.001].The hospitalization costs were significantly higher in the three-endoscope group than those in the two-endoscope group[39 316.0(32 338.5,43 421.0)yuan vs.33 717.0(30 873.3,37 813.3)yuan,Z=-3.272,P=0.001].There were no significant differences in the incidence of postoperative pancreatitis[2.5%(1/40)vs.2.5%(1/40),χ2=0.000,P=1.000],the incidence of bile leakage[7.5%(3/40)vs.2.5%(1/40),χ2=0.263,P=0.615],and residual stone rate[7.5%(3/40)vs.0.0%(0/40),P=0.241]between the two groups.Forty cases in the three-endoscope group were followed up for 2-20 months,with a median of 13 months.One case of stone recurrence occurred at 8 months after surgery.Forty patients in the two-endoscope group were followed up for 1-21 months,with a median of 15 months.There was 1 case of stone recurrence at 6 and 10 months postoperatively,respectively.There was no statistically significant difference in stone recurrence rate between the two groups[2.5%(1/40)vs.5.0%(2/40),χ2=0.000,P=1.000].Conclusions LC+LCBDE combined with holmium laser lithotripsy,primary closure of the common bile duct,ERCP,and ENBD in the treatment of cholecystolithiasis and choledocholithiasis can shorten the hospitalization time.The replacement of T-tube with nasobiliary duct protects the function of the Oddi sphincter,which is more in line with the concept of minimally invasive surgery and worthy of clinical application.