ObjectiveTo verify the technical feasibility and safety of partial nephrectomy in experimental pigs using a single-port endoscopic surgical robot in a transcontinental ultra-remote environment spanning 13 000 km with an average network delay of 204 ms, and to explore a dynamic combined anesthesia strategy that can effectively prevent intraoperative body movement in animals. MethodsThe research team used one experimental pig in Shanghai, China, and one in Orlando, the United States, and performed bidirectional remote surgery using the same model of single-port endoscopic surgical robot system. The anesthesia regimen included preoperative administration of 0.02 mg/kg dexmedetomidine hydrochloride and 0.05 mg/kg fentanyl citrate for combined sedation and analgesia. During remote surgery, according to the animal's reflex activity, pain response, and train-of-four stimulation (TOF) count results, vecuronium bromide was continuously infused at an initial rate of 0.04 mg·kg^-1·h^-1, and the dose was dynamically adjusted. Together with isoflurane inhalation anesthesia, the animal was maintained in a deep neuromuscular block state (TOF=0) to prevent intraoperative body movement. In addition, heart rate, blood pressure, muscle relaxation, and other indicators were monitored throughout the operation. ResultsSurgical operations were successfully performed at both sites, and the network delay remained stable at 202-208 ms. There was no data packet loss and no robot equipment failure. The vital signs of the experimental animal in Shanghai, China, remained stable, with zero body movement throughout the operation. Intraoperative blood loss was controllable, and no abnormal bleeding occurred. ConclusionIn transcontinental ultra-remote robotic surgery with inherent network delay, a dynamically adjusted anesthesia strategy can effectively avoid accidental bleeding caused by animal body movement and reduce the risks associated with network latency, thereby verifying the feasibility of this technical approach. In the future, it will be necessary to build a real-time cross-regional physiological data synchronization platform, standardize anesthesia protocols for animals undergoing remote surgery, and provide a technical basis for clinical translation to human trials.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To observe the effects of Ditan Yizhi Decoction on mitochondrial dynamics-mediated glucose metabolism in vascular dementia(VaD)rats based on the ROS/Drp1 axis;To explore its mechanism in treating VaD.Methods Ten male SD rats were randomly selected from 70 as the sham-operation group,and VaD models were prepared using the modified bilateral common carotid artery permanent ligation method for the remaining rats.The successfully modeled rats were randomly divided into model group,positive drug group(donepezil hydrochloride),inhibitor group(Mdivi-1)and Ditan Yizhi Decoction low-,medium-and high-dosage groups(12.86,25.725,51.45 g/kg),and intervened with corresponding method for 4 consecutive weeks.Morris water maze experiment was used to assess the learning memory ability of rats,HE and Nissl staining were used to observe the morphology of hippocampal tissue,transmission electron microscopy was used to observe the mitochondrial ultrastructure of hippocampal neurons,DHE fluorescent probe was used to detect the content of ROS in hippocampal neurons,Western blot was used to detect the expressions of Drp1,p-Drp1,Mfn2,Opa1,HK1,PKM2,GLUT1 and LDHA,the contents of serum IL-1β,IL-6 and TNF-α were detected by ELISA.Results Compared with the sham-operation group,rats in the model group had a prolonged escape latency(P<0.01)and a reduced number of crossing platforms(P<0.01);neuronal gaps in the CA1 region of the hippocampus were enlarged,with irregular cell morphology and blurred borders,neuronal consolidation,lysis and fragmentation of Nissl bodies and reduced number of Nissl bodies,swelling and deformation of mitochondria,disorganization of the cristae,and disruption of the bilayer membrane structure;the content of ROS in CA1 region of the hippocampus was elevated,the protein expressions of Mfn2 and Opa1 significantly decreased(P<0.01),the expressions of p-Drp1,HK1,PKM2,GLUT1,LDHA proteins significantly increased(P<0.01),and serum contents of IL-1β,IL-6 and TNF-α significantly increased(P<0.01).Compared with the model group,the escape latency was significantly shortened in Ditan Yizhi Decoction groups,positive drug group and inhibitor group(P<0.01),and the number of crossing platforms increased(P<0.05,P<0.01);the number of neurons in the hippocampal CA1 region increased,with normal morphology,orderly arrangement,abundant Nissl bodies,recovered mitochondrial morphology,and decreased rupture;the ROS content in hippocampal CA1 region decreased(P<0.01),while the expressions of Mfn2 and Opa1 proteins increased(P<0.01),the expressions of p-Drp1,HK1,PKM2,GLUT1 and LDHA proteins decreased(P<0.01),and the serum contents of IL-1β,IL-6 and TNF-α decreased(P<0.05).Conclusion Ditan Yizhi Decoction can improve cognitive impairment and neuronal morphology in VaD rats,and the mechanism maybe related to regulation of mitochondrial dynamics through the ROS/Drp1 axis,attenuating glycometabolic disorders,and reducing inflammatory response.

Objective:Committee of Minimally Invasive Cardiovascular Surgery(CMICS) conducts an annual summary of minimally invasive cardiovascular surgery procedures performed throughout the country, which includes a comprehensive survey of the total number of minimally invasive procedures by region and the distribution of minimally invasive procedures by hospital. Since CMICS first published the 2018-2019 China Minimally Invasive Cardiovascular Surgery Data White Paper in 2020, the report has received great attention from peers within and outside the industry. In this statistical report, CMICS will focus on publishing the data related to minimally invasive cardiovascular surgery in China from 2021 to 2023 for reference and use by industry peers.

Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

OBJECTIVE: To explore the clinical features of patients with necrotizing soft tissue infection (NSTI) and the related factors for sepsis, so as to provide a basis for early intervention and improvement of patients' prognosis. METHODS: A retrospective case series study was conducted to analyze the clinical data of NSTI patients admitted to the department of burns and wound repair surgery of Guangdong Provincial People's Hospital from October 2021 to December 2024. Demographic information, underlying diseases, infection characteristics, laboratory test results and etiological findings at admission, treatment status, occurrence of complications (including sepsis) and prognosis were collected. Univariate and multivariate Logistic regression analyses were used to identify the associated factors for sepsis in NSTI patients. Receiver operator characteristic curves (ROC curves) were plotted to evaluate the predictive value of individual and combined factors for sepsis. RESULTS: A total of 159 NSTI patients were enrolled, mainly middle-aged and elderly males. Most patients had comorbidities, including diabetes mellitus (110 cases, 69.2%) and hypertension (67 cases, 42.1%). The main infection site was the lower extremities (104 cases, 65.4%). Common symptoms included redness (96 cases, 60.4%), swelling (129 cases, 81.1%), local heat (60 cases, 37.7%), pain (100 cases, 62.9%), and skin ulceration or necrosis (9 cases, 5.7%). Imaging findings included soft tissue swelling (66 cases, 57.9%), gas accumulation (41 cases, 36.0%), and abnormal signal/density shadows (50 cases, 43.9%). Staphylococcus aureus was the main pathogenic bacterium [12.0% (31/259)], and drug-resistant Escherichia coli had the highest detection rate among drug-resistant bacteria [35.1% (13/37)]. Regarding debridement and repair, most patients (80 cases, 50.3%) underwent debridement ≥ 72 hours after admission, while only 10.1% (16 cases) received debridement within 6 hours. Most patients underwent multiple debridements, with 2 times of debridements being the most common (68 cases, 42.8%), and the maximum times of debridements reached 6. The largest number of patients received secondary suture (44 cases, 27.7%). In terms of complications, sepsis was the most common (66 cases, 41.51%), followed by acute kidney injury, respiratory failure requiring mechanical ventilation, and multiple organ dysfunction syndrome (MODS), while disseminated intravascular coagulation (DIC) was the least common. During the follow-up period, 9 patients (5.66%) were readmitted within 90 days, and 11 patients died, with a mortality rate of 6.92%. Univariate analysis showed that diabetes, coronary heart disease, gout, body temperature, heart rate, C-reactive protein, platelet count, total bilirubin, albumin, creatinine, out-of-hospital treatment, and out-of-hospital use of antimicrobial agents were significantly associated with sepsis in NSTI patients (all P < 0.05). Multivariate Logistic regression analysis showed that coronary heart disease [odds ratio (OR) = 30.085, 95% confidence interval (95%CI) was 2.105-956.935], C-reactive protein (OR = 1.026, 95%CI was 1.009-1.054), and total bilirubin (OR = 1.436, 95%CI was 1.188-1.948) were independent associated factors for sepsis in NSTI patients (all P < 0.05). ROC curve analysis revealed that the combination of the three predictors yielded the highest AUC for predicting sepsis in NSTI patients compared to any individual predictor [area under the curve (AUC) = 0.799 (95%CI was 0.721-0.878)]. CONCLUSIONS The clinical features of NSTI patients show certain regularity. Coronary heart disease, C-reactive protein, and total bilirubin are independent associated factors for sepsis in NSTI patients.
Humans ; Retrospective Studies ; Male ; Sepsis ; Soft Tissue Infections/microbiology* ; Female ; Middle Aged ; Aged ; Adult ; Prognosis ; Risk Factors ; Necrosis ; Logistic Models ; Fasciitis, Necrotizing

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.