OBJECTIVE To compare the clinical efficacy and safety of remimazolam and propofol in general anesthesia induction and maintenance for elderly patients undergoing thoracoscopic lobectomy. METHODS A total of 86 elderly lung cancer patients who underwent thoracoscopic lobectomy at Chongqing University Three Gorges Hospital from February to July 2024 were selected and divided into the propofol group and the remimazolam group according to the randomized numerical table method， with 43 cases in each group. During anesthesia induction， patients in the propofol group and the remimazolam group were intravenously administered 2 mg/kg of Propofol medium- and long-chain fat emulsion injection or 0.25 mg/kg of Remimazolam tosilate for injection， respectively； during anesthesia maintenance， the two groups received intravenous infusion of 6-10 mg/（kg·h） of Propofol medium- and long- chain fat emulsion injection or 1-3 mg/（kg·h） of Remimazolam tosilate for injection， respectively. The anesthesia effects， anesthesia-related indicators， intraoperative opioid and muscle relaxant dosages， Ramsay sedation score， numerical rating scale （NRS） score， and hemodynamic parameters were compared between the two groups， and the occurrence of adverse drug reactions was recorded. RESULTS A total of 41 patients in the propofol group and 43 patients in the remimazolam group completed the trial. The proportion of patients with grade Ⅰ anesthesia effect in the remimazolam group was significantly higher than that in the propofol group， while the proportion of patients with grade Ⅱ anesthesia effect was significantly lower than that in the propofol group （P＜0.05）. In this group， the disappearance time of eyelash reflex， the time taken for the bispectral index to drop to 60， and the Ramsay sedation scores （2 and 6 hours after operation） were all significantly prolonged or increased， while the recovery time， NRS scores （2 and 6 hours after operation）， and the incidence of intraoperative hypotension were all significantly shortened or reduced； moreover， the improvements of the above sedation/NRS scores exhibited a time-dependent pattern within 2 to 24 hours after operation （P＜0.05）. Compared with before anesthesia induction （T0）， the heart rate [except at 2 min after medication （T1）， 60 min after anesthesia （T4）， and at the end of surgery （T5） in the remimazolam group] and mean arterial pressure [except at T1 in the remimazolam group] of patients in both groups significantly decreased at T1， 5 min after medication （T2）， at the start of surgery （T3）， T4， and T5 （P＜0.05）. Meanwhile， regional cerebral oxygen saturation significantly increased in both groups. Furthermore， the heart rate and mean arterial pressure of patients in the remimazolam group were significantly higher than those in the propofol group at T1， T2 and T4 （P＜0.05）. No statistically significant differences were observed between the two groups in terms of postanesthesia care unit stay time， dosage of opioids and muscle relaxants， regional cerebral oxygen saturation， or peripheral oxygen saturation at various time points （P＞0.05）. CONCLUSIONS Compared to propofol， remimazolam demonstrates superior anesthesia effects when used for the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy. It not only provides more stable intraoperative hemodynamics and shortens the postoperative recovery time but also effectively reduces the incidence of intraoperative hypotension.

Objectives:To compare the efficacy of the combination of excimer laser coronary angioplasty(ELCA)and drug-coated balloon(DCB)for in-stent restenosis(ISR)and to evaluate the impact of neointimal tissue characteristics on treatment outcomes. Methods:A total of 96 ISR lesions from 86 patients who underwent optical coherence tomography(OCT)evaluation and DCB with or without ELCA treatment at The First Medical Center of Chinese PLA General Hospital from January 2019 to May 2023 were retrospectively analyzed.ISR lesions were divided into ELCA+DCB group(n=30)and DCB group(n=66).Additionally,ISR lesions were classified as homogeneous and non-heterogeneous patterns based on the OCT characteristics of the neointimal tissue,and the impact on acute lumen gains was compared between different ISR patterns.Acute lumen gain(ΔMLA)was defined as the changes in minimum lumen area before and after the intervention. Results:The ELCA+DCB group had a significantly greater ΔMLA than the DCB group([3.2±0.8]mm2 vs.[2.6±1.4]mm2,P=0.015).Among the ISR with a homogeneous pattern,the ΔMLA of the ELCA+DCB group was significantly greater than that of the DCB group([3.0±0.9]mm2 vs.[2.2±1.1]mm2,P=0.030).There was no significant difference in ΔMLA between the two ISR groups with the non-homogeneous pattern([3.4±0.7]mm2 vs.[3.2±1.5]mm2,P=0.533).There was no death,the rate of target lesion revascularization was similar between the patients with lesions receiving DCB treatment and patients receiving ELCA +DCB treatment(7.4%vs.4.2%,P＞0.05). Conclusions:The combination of ELCA and DCB is an effective strategy for treating ISR,which can achieve greater acute lumen gain compared to DCB treatment alone,especially for the treatment of homogenous ISR pattern characterized by OCT.

OBJECTIVE To analyze the accumulation law of saponins during growth in Paris polyphylla Smith var. chinensis (Franch.) Hara, determine the content of the main saponins in different cultivation years, age groups, cultivation modes and provenances. METHODS The content of 5 kinds saponins(I, II, VI, VII, H) was simultaneous determined by HPLC. RESULTS The total saponins in P. polyphylla Smith var. chinensis (Franch.) Hara were mainly composed of saponin VII and H, supplemented by saponin VI, I and II. The content of saponins(I, II, VII) was significantly different among different cultivation years rhizome, while it reached the standard of Chinese Pharmacopoeia 2020 Edition after 6 years old, 8-year-old rhizome was the highest. The saponins(I, II, VII) content in 4a rhizome and 5a rhizome was significant higher than others, and it ranged from 0.354% to 0.765% in different cultivation modes, from high to low as follows: coniferous forest>bamboo forest>broadleaf forest>greenhouse. In different provenances, it ranged from 0.592% to 0.741%, reached the highest level in Qingyuan Baikan, and was slightly lower than the standard of Chinese Pharmacopoeia 2020 Edition in Sanming Fujian. CONCLUSION There are remarkable correlations among saponins accumulation amounts and cultivation years, age groups, cultivation modes and provenances, which can provide reference for the artificial culvication of P. polyphylla Smith var. chinensis (Franch.) Hara.

OBJECTIVE To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method for determination and comparison of 26 components in different parts of two base plants of Shiliang tea(Chimonanthus salicifolius S.Y.Hu and Chimonanthus zhejiangensis M.C.Liu), and screen quality markers of different parts. METHODS The UHPLC method was performed on an Agilent RRHD Eclipse Plus C18 (2.1 mm×50 mm, 1.8 μm) column with a gradient elution of methanol and 0.1% formic acid in water at a flow rate of 0.3 mL·min−1, the column temperature was 35 ℃, and the injection volume was 0.5 μL; the multiple reaction monitoring mode was employed for the quantification of 26 components with electrospray ionization(ESI) source polarity in negative and positive mode. RESULTS Good linear relationship(r >0.999) were observed in the test ranges for 26 compounds, and the average recovery was 88.5%−111.7% with RSD was 3.4%−9.8%. There was no significant difference between the two base plants of Shiliang tea, and all of these samples were divided into two categories by hierarchical cluster analysis. The main components in leaves was flavonoids, among them, the content of kaempferol 3-O-rutinoside was the highest, reaching 12.902 mg.g−1; the main components in stems and roots was coumarins, and the content of alkaloids in roots was higher, relatively; 7 quality markers of difference were screened by OPLS-DA, which were kaempferol 3-O-rutinoside, chimonanthine, rutin, fraxetin, calycanthoside, scopolin, neochlorogenic acid. CONCLUSION These study elucidates the differences of chemical components in the different parts of two base plants of Shiliang tea, which providing basis for the research of pharmacodynamic substances and references for the comprehensive utilization of Chimonanthus salicifolius S.Y. Hu and Chimonanthus zhejiangensis M.C.Liu resources.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting,coagulation,and thermal injury of ex vivo animal tissues,aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia.Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment,respectively.Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s.The effects of layers at powers of 60,90,120,150,and 160 W on tissue injury were observed.Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury.Additionally,in coagulation mode,the effects of 30,40,and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5,10,and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue,the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue.However,at a distance of 0.5 cm,the 120 W,150 W,or 160 W lasers caused slight damage to the bladder tissue.In addition,with the increase in output power,the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased,showing a good linear correlation between vaporization volume and total energy consumption(P＜0.001).Histopathological HE staining results indicated that the coagulation layer thickness in the experimental group was 292.20-309.98 μm,and the vaporization layer depth was 1.49-4.52 mm.In the control group,the coagulation layer thickness was 289.91-303.53 μm,and the vaporization layer depth was 1.88-4.43 mm.There was no significant difference between the two groups(P＞0.05).Moreover,when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2,the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power(P＜0.05).The coagulated layer thickness in the experimental group was 496.04-514.47 μm,while that in the control group was 489.39-518.53 μm.Additionally,in coagulation mode,when ex vivo pig kidney tissue was irradiated for 5,10,and 15 s with 30,40,and 50 W semiconductor lasers,the coagulation diameter,groove depth,and coagulation efficiency gradually increased with the increase in laser output power(P＜0.05).The coagulation layer thickness in the experimental group and control group was 399.10-449.98 μm and 392.97-447.65 μm,respectively,and the vaporization layer depth was 3.05-7.09 mm and 2.70-7.14 mm,respectively.There was no significant difference between the two groups(P＞0.05).Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation,cutting,and coagulation effect on ex vivo tissues,with a good linear correlation between the effect and the output energy.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates(PRFr)treatment on the KOA process,we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution.Methods Twenty-four WHBE rabbits were randomly divided into three groups:normal control(NC)group(n=6),model(KOA)group(n=12),and cure(PRFr)group(n=6).KOA and PRFr groups were injected with 0.5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days,respectively.At 4 and 8 weeks of modeling,the knee joint grade scoring,X-ray imaging,and gross scoring were performed.Serum levels of IL-1β,TNF-α,and MMP-13 were measured by ELISA.At 4 weeks,6 animals in the KOA group were euthanized,and at 8 weeks,the remaining animals in each group were euthanized.Pathological sections were prepared after decalcification,and then HE,toluidine blue,and safranin O-fast green staining and immunohistochemical analysis of TGF-β,BMP3,and NF-κB were conducted.Results The Lequesne MG behavioral score,Mankin's score,and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group(P＜0.01).Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes.These result indicated that the KOA model was established successfully.In KOA rabbits,knee joint swelling,joint pain stimulation,and movement limitation were obvious.X-rays showed a high-density soft tissue shadow,indicating more joint effusion and a rough articular surface in general.After PRFr treatment,the serum levels of proinflammatory factors IL-1β,TNF-α,and MMP-13 in KOA model rabbits were significantly reversed(P＜0.05,P＜0.01).Additionally,the cartilage surface became smooth,and most chondrocytes were neatly distributed.Expression levels of TGF-β,BMP3,and NF-κB induced by KOA were also significantly decreased(P＜0.01).Conclusions We successfully established a KOA model in WHBE rabbits,and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/BMP and NF-κB pathways.

Objective To evaluate the effectiveness of a 1470 nm semiconductor laser therapeutic instrument(referred to as a curestar therapeutic instrument)for prostatectomy in Beagle dogs.Methods Twenty-eight adult male Beagle dogs were randomly divided into three groups:sham(n=3),experimental(n=15),and control(n=10).The experimental group was further divided into three subgroups:120 W/50 W,150 W/50 W,and 160 W/50 W for vaporization cutting/coagulation hemostasis.The control group was divided into two subgroups:120 W/50 W and 150 W/50 W with five in each subgroup.Experimental and control groups underwent canine prostatectomy through the entrance of the bladder neck under electrocision.The operational suitability and effectiveness of the product during surgery were assessed.After the operation,the general condition of the dogs was observed,and blood biochemical and hematological indicators were measured before,immediately after,and at 3,7,and 28 days after the operation.At 1 h and 4 weeks after surgery,B-ultrasound and electric resection were performed under anesthesia to observe the conditions of the urethra and prostate,and prostatic tissue was subjected to HE staining for pathological observations.The thickness of the coagulation layer at 1 h after the operation and repair of the urothelial epithelium at 4 weeks were analyzed.Results During the operation,experimental and control groups had good operability and showed good vaporization cutting and coagulation hemostasis performance.After the operation,no significant effects were observed on the general condition,and blood biochemical and hematological indicators of the dogs.Ultrasound showed that the urethral expansion was visible immediately after the operation,and the echo of the urethral epithelium was slightly enhanced.At 4 weeks,the prostate tissue had a slightly low echo with uniformly distributed small point-like echoes inside,and the capsule had a linearly high echo,consistent with the sham group.The weight of the vaporized prostate tissue in experimental and control groups was 0.91～1.33 g with a resection rate of 17.11％～20.27％.As the power of vaporization cutting increased,the laser emission time gradually decreased,while the vaporization cutting speed and efficiency both increased.However,no significant difference was found between experimental and control groups(P＞0.05).Under the electrocision microscope,a burn-like change was observed in the surgical wounds of the prostate urethra in experimental and control groups at 1 h after surgery,and the boundary between the wound and normal urothelium was visible.At 4 weeks,the urothelium of the prostate had been repaired and flattened,and the boundary with the surrounding normal urothelium was blurred.Similarly,pathological observations showed that experimental and control groups had significant damage to the prostate urethral orifice at 1 h after surgery with a small amount of carbonization and coagulative necrosis on the surface of the wound,a small amount of inflammatory cell infiltration,and a coagulation layer thickness of approximately 0.4 mm.At 4 weeks,the prostate urethral morphology of the sham group was normal,whereas experimental and control groups showed new epithelial growth covering the wound with a uniform thickness and no coagulative necrosis tissue attached to the wound.A mild inflammatory reaction was still present in the surrounding area,fibroblast proliferation was obvious,and stromal and epithelial cell proliferation was visible in the surrounding prostate,some of which showed squamous metaplasia.The prostate capsule was intact and the morphology of the surrounding nerves and blood vessels was normal.Conclusions The curestar therapy instrument is effective for prostatectomy in Beagle dogs with good vaporization cutting and coagulation hemostasis performance.No significant difference was found in postoperative physiological indicators compared with the sham group.

Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.

Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.