Background and Aims:In recent years,with the continuous progress of systemic therapy,hepatic arterial infusion chemotherapy(HAIC)combined with immune checkpoint inhibitors and anti-angiogenic agents has demonstrated significant efficacy in the treatment of advanced hepatocellular carcinoma(HCC).However,direct comparisons between different immunotherapeutic targets,such as PD-1 and PD-L1 inhibitors,in terms of clinical benefit and safety remain limited.This study aimed to compare the efficacy and safety of HAIC plus bevacizumab and sintilimab(HAIC-BP1)versus HAIC plus bevacizumab and atezolizumab(HAIC-BPL)in advanced HCC.Methods:A retrospective analysis was conducted on 88 patients with advanced HCC who received first-line HAIC-BP1or HAIC-BPL at Sun Yat-sen University Cancer Center between January 2020 and December 2022.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR),disease control rate(DCR),and adverse events(AEs)were compared between the two groups.Cox regression analysis was performed to identify prognostic factors affecting PFS.Results:A total of 47 patients were included in the HAIC-BP1 group and 41 patients in the HAIC-BPL group,with no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The ORR(59.6%vs.65.9%)and DCR(72.3%vs.80.5%)did not significantly differ between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).After a median follow-up of 16.3 months,there were no significant differences in median OS(21.3 months vs.22.4 months)or median PFS(6.7 months vs.6.2 months)between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).The incidence of AEs was similar,and no treatment-related deaths occurred.Multivariate Cox regression analysis identified tumor diameter>10 cm as an independent adverse prognostic factor for PFS(HR=0.48,95%CI=0.27-0.83,P=0.009).Conclusion:Both HAIC-BP1 and HAIC-BPL demonstrated comparable efficacy and favorable safety profiles as first-line treatment options for advanced HCC.Tumor diameter>10 cm was an independent unfavorable prognostic factor for PFS,underscoring the importance of patient stratification in clinical decision-making.

[Objective]To evaluate the efficacy of ureteral dilation versus ureteral reimplantation in treating pediatric primary obstructive megaureter(POM).[Methods]A retrospective analysis was conducted on clinical data of 53 pediatric patients with POM treated in the Department of Urology,Anhui Provincial Children's Hospital from April 2019 to September 2023.The cohort included 37 boys and 16 girls with 5 bilateral and 48 unilateral cases.The age ranged from 1 to 157 months,with a median age of 17.00(5.50-48.00)months.Patients were assigned to 3 groups based on the management of the ureteral stricture segment:dilation group(18 cases,19 sides),Cohen group(20 cases,24 sides),and Lich-Gregoir group(15 cases,15 sides).The duration of the operations,postoperative hospital stays,postoperative indwelling catheters,postoperative D-J stents;changes in renal pelvis anteroposterior diameter and ureteral diameter;and postoperative complications were compared to evaluate the therapeutic effects.[Results]All 53 patients successfully underwent surgery.The dilation group showed significantly shorter operative time,postoperative hospital stay,and postoperative catheterization duration compared to the Cohen and Lich-Gregoir groups(P＜0.05).However,the postoperative D-J stent time was longer in the dilation group than in the other 2 groups(P＜0.05).Upon follow-ups for 6-12 months after stent removal,all groups demonstrated statistically significant reductions in renal pelvis anteroposterior diameter and ureteral diameter compared to preoperative values(P＜0.05).No significant differences were observed among the 3 groups in hydronephrosis resolution rates(P＞0.05).Additionally,the incidence of postoperative complications(urinary tract infection,vesicoureteral reflux,and reoperation for restenosis)did not differ significantly among the groups(P＞0.05).[Conclusions]Ureteral dilation demonstrated non-inferior short-term clinical efficacy compared to ureteral reimplantation in managing POM in pediatric patients.With reduced operative time,minimal invasiveness,and technical simplicity,ureteral dilation may be considered a preferential treatment option for children with POM.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Background and Aims:In recent years,with the continuous progress of systemic therapy,hepatic arterial infusion chemotherapy(HAIC)combined with immune checkpoint inhibitors and anti-angiogenic agents has demonstrated significant efficacy in the treatment of advanced hepatocellular carcinoma(HCC).However,direct comparisons between different immunotherapeutic targets,such as PD-1 and PD-L1 inhibitors,in terms of clinical benefit and safety remain limited.This study aimed to compare the efficacy and safety of HAIC plus bevacizumab and sintilimab(HAIC-BP1)versus HAIC plus bevacizumab and atezolizumab(HAIC-BPL)in advanced HCC.Methods:A retrospective analysis was conducted on 88 patients with advanced HCC who received first-line HAIC-BP1or HAIC-BPL at Sun Yat-sen University Cancer Center between January 2020 and December 2022.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR),disease control rate(DCR),and adverse events(AEs)were compared between the two groups.Cox regression analysis was performed to identify prognostic factors affecting PFS.Results:A total of 47 patients were included in the HAIC-BP1 group and 41 patients in the HAIC-BPL group,with no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The ORR(59.6%vs.65.9%)and DCR(72.3%vs.80.5%)did not significantly differ between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).After a median follow-up of 16.3 months,there were no significant differences in median OS(21.3 months vs.22.4 months)or median PFS(6.7 months vs.6.2 months)between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).The incidence of AEs was similar,and no treatment-related deaths occurred.Multivariate Cox regression analysis identified tumor diameter>10 cm as an independent adverse prognostic factor for PFS(HR=0.48,95%CI=0.27-0.83,P=0.009).Conclusion:Both HAIC-BP1 and HAIC-BPL demonstrated comparable efficacy and favorable safety profiles as first-line treatment options for advanced HCC.Tumor diameter>10 cm was an independent unfavorable prognostic factor for PFS,underscoring the importance of patient stratification in clinical decision-making.

Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

Objective To investigate the therapeutic effects and underlying mechanisms of Ganluqingwen formula on lipopolysaccharide(LPS)-induced acute lung injury/acute respiratory distress syndrome(ALI/ARDS)in mice.Methods Fifty ICR mice were randomly divided into five groups:control,model,and Ganluqingwen formula(GLQW)low dose(7.10 g/kg),medium dose(15.21 g/kg),and high dose(30.42 g/kg)groups,with 10 mice per group.On days 1-3,mice in GLQW groups were daily gavaged with the corresponding dose of GLQW,while control and model groups received equal volumes of saline.On day 4,ALI/ARDS was induced in model and GLQW groups using intraperitoneal injection of LPS(20 mg/kg),while control group received an equal volume of PBS.At 24 h post-treatment,survival rate,wet-to-dry weight ratio(W/D)and lung histological changes(HE staining)were observed.Serum levels of tumor necrosis factor(TNF)-α,interferon gamma(IFN-γ),interleukin(IL)-4,IL-10,IL-12,as well as lung tissue levels of TNF-α,IFN-γ,IL-1β,IL-4,IL-6,IL-10 were measured by ELISA.Western blotting was used to determine the expression levels of NOD-like receptor thermal protein domain associated protein 3(NLRP3),cystatinase-1(Caspase-1),apoptosis-associated speck-like protein(ASC),and membrane perforating protein Gasdermin D(GSDMD)in lung tissue.Results No significant differences in survival rates were observed among the groups(P>0.05).Compared with control group,ELISA and Western blotting results showed that lung tissue W/D,IFN-γ,TNF-α,IL-4,IL-12,IL-1β,IL-6,NLRP3,ASC,and Caspase-1,GSDMD and serum IFN-γ,TNF-α,IL-4,IL-12 levels were significantly higher(P<0.05),and IL-10 levels in lung tissue and serum were significantly lower in mice of model group(P<0.05).Compared with model group,lung tissue W/D,IFN-γ,TNF-α,IL-1β,IL-4,IL-6,IL-12,NLRP3,ASC,Caspase-1,and GSDMD,and serum IFN-γ,TNF-α,IL-4,and IL-12 levels were significantly lower(P<0.05),and lung tissue IL-10 levels were significantly higher(P<0.05)in GLQW low,medium,and high dose groups,with high-dose group showing significantly higher level in serum IL-10(P<0.05).Compared with GLQW low-dose group,the lung tissue levels of IFN-γ,IL-6,NLRP3,ASC,Caspase-1,and GSDMD,and serum TNF-α were significantly lower(P<0.05),and lung and serum IL-10 levels were significantly higher in GLQW high-dose group(P<0.05).HE staining results showed that lung structure was clear and normal in control group;part of the lung interstitium was congested and hemorrhagic,and some of the fine bronchial periphery was infiltrated with inflammatory cells in model group;the phenomena of lung interstitial congestion and hemorrhage were reduced,and the degree of infiltration of inflammatory cells was alleviated in GLQW low-,medium-,and high-dose groups.Conclusion Ganluqingwen formula can delay the development of ALI/ARDS in mice by inhibiting NLRP3/Caspase-1/GSDMD pathway,thereby suppressing cellular pyroptosis.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

Objective:To elucidate the mechanism of acute lung injury (ALI) by investigating the relationship of sirtuin 6 (SIRT6) with lactylation of mitochondrial fission 1 protein (FIS1) and mitophagy in mice.Methods:Twenty-four SPF-grade healthy wild-type C57BL/6 mice of either sex, aged 6-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) using a table of random numbers: sham operation group (group S), ALI group, ALI + agonist group (group AA), and ALI+ agonist+ lactate group (group AAL). The mouse ALI model was established by intratracheal instillation of lipopolysaccharide 5 mg/kg in anesthetized animals. Immediately after developing the model, UBCS039 30 mg/kg was injected via the tail vein in group AA, UBCS039 30 mg/kg was injected via the tail vein and L-lactic acid sodium 1 mg/g was intraperitoneally injected in group AAL, and vehicle 0.5 ml was given instead in group S. Another 6 Prkn-/- mice were selected and assigned to Prkn-/-+ ALI+ agonist group (group PAA), and UBCS039 30 mg/kg was injected via the tail vein immediately after developing the ALI model. The mice were anesthetized and sacrificed at 12 h after lipopolysaccharide instillation, and the lung tissue was obtained for determination of the FIS1 lactylation and ubiquitination levels, the binding levels of FIS1 to SIRT6 and Parkin (using co-immunoprecipitation), expression of PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), and mitochondrial Parkin (by Western blot) and for microscopic examination of the pathological changes (after haematoxylin and eosin staining) which were scored. The wet/dry lung weight (W/D) ratio was calculated, and the apoptosis rate of cells in lung tissues was calculated by TUNEL assay. Results:Compared with group S, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased in group ALI ( P<0.05). Compared with group ALI, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly decreased, the binding level of FIS1 to Parkin and FIS1 ubiquitination level were increased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was up-regulated in group AA ( P<0.05). Compared with group AA, the FIS1 lactylation level was significantly increased, and the binding level of FIS1 to Parkin was decreased in group AAL, and the W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased, the FIS1 ubiquitination level was decreased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was down-regulated in group AAL and group PAA ( P<0.05). Conclusions:SIRT6 inhibits FIS1 lactylation, increases the binding of FIS1 to Parkin, and thus promotes mitophagy, which is involved in the process of ALI in mice.

Objective To develop a carriage-type field operating unit with advantages in mobility and rapid deployment to solve the problems of the traditional field operating equipment in flexibility and environmental adaptability.Methods The carriage-type field operating unit was made based on a BEIBEN TRUCK transport vehicle platform with external and internal modifications.The external modification involved a hydraulic loading platform with a capacity of 2 t and electric lifting function at the rear of the carriage and an external equipment compartment at the bottom.The internal modification included area renovation,tarp modification,facility remodeling and equipment configuration.Results The carriage-type field operating unit behaved better than the traditional field operating vehicle and operating shelter in deployment time,infection control,mobility,temperature control,etc.Conclusion The carriage-type field operating unit gains advantages in mobility,rapid deployment and complete supporting facilities,and can be used as a relatively independent field surgical unit.[Chinese Medical Equipment Journal,2025,46(8):113-117]

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.