In tracheal resection and reconstruction, a technically demanding, complex, and high-risk procedure, management of the anastomotic site significantly impacts postoperative outcomes and long-term quality of life. However, comprehensive studies detailing perioperative anastomotic management strategies in tracheal reconstruction remain scarce. This review summarizes perioperative management strategies for tracheal reconstruction, covering preoperative assessment, surgical techniques, and other key aspects. It also highlights future research directions and challenges, aiming to provide clinicians with a systematic guide to perioperative management in tracheal reconstruction.

Objective To investigate the effect of ATP synthase inhibitory factor 1 (ATPIF1) on the antitumor activity of chimeric antigen receptor (CAR)-NK92 cells. Methods HER2-targeted CAR-NK92 cells with ATPIF1 overexpression or knockdown were constructed. CAR-positive expression rate was detected by flow cytometry. Cell proliferation capacity was measured using CCK-8 assay. Glycolytic capacity was analyzed by Seahorse metabolic analyzer. Mitochondrial membrane potential levels were detected using JC-1 probe. Target cell lysis rate was evaluated by firefly luciferase reporter assay. Expression levels of CD107a, natural-killer group 2 member D (NKG2D), granzyme B (GzmB), perforin, and interleukin 2 (IL-2) were detected via flow cytometry. Quantitative real-time PCR was used to measure the expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), tumor necrosis factor α (TNF-α), ATPIF1, and hexokinase 1 (HK1). The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined. Results Successfully generated HER2-targeting control CAR-NK92 cells, as well as ATPIF1-overexpressing and ATPIF1 knockdown CAR-NK92 cells. The ATPIF1-overexpressing CAR-NK92 cells showed significantly enhanced target cell lysis rate, elevated expression levels of NKG2D and CD107a, increased secretion capacities of Granzyme B (GzmB) and IL-2, and upregulated mRNA expression levels of IFIT1 and TNF-α, while ATPIF1-knockdown cells exhibited opposite effects. ATPIF1 overexpression induced metabolic reprogramming in CAR-NK92 cells, manifested by significantly decreased mitochondrial membrane potential (δpsim), markedly upregulated HK1 mRNA expression, and enhanced basal glycolysis and glycolytic capacity. After glycolysis inhibition with 2-DG (5 μmol/L), both ATPIF1-overexpressing and knockdown CAR-NK92 cells showed no significant differences in NKG2D and CD107a expression levels compared to control cells. Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.
Humans ; Glycolysis ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Granzymes/genetics* ; Hexokinase/metabolism* ; Cell Line, Tumor ; Interleukin-2/genetics* ; Cell Proliferation ; NK Cell Lectin-Like Receptor Subfamily K/genetics* ; Membrane Potential, Mitochondrial

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

This study investigated the specific immune response of BALB/c mice that was induced by a circular RNA (circRNA) vaccine expressing the herpes simplex virus type II (HSV-2) glycoprotein D (gD). The aim was to evaluate the immunological potential of this vaccine and lay a foundation for developing an mRNA vaccine against HSV-2. PCR and homologous recombination were employed to integrate the gD gene obtained from the pT7AMP-gD ectodomain plasmid into pUC57 to generate the recombinant plasmid pUC57-circ-gD, which was then sequenced and characterized. In vitro transcription and cyclization were performed on the template DNA to generate pUC57-circ-gD mRNA. To validate the formation of circular RNA, we cleaved the pUC57-circ-gD mRNA with RNase R and employed RT-PCR to validate the cyclization. The pUC57-circ-gD mRNA was then transfected into 293T cells. After 72 h, the cell supernatant was collected, and Western blotting was employed to measure the protein level of gD. Subsequently, the mRNA was encapsulated in lipid nanoparticles (LNPs) by microfluidic encapsulation. BALB/c mice were administrated with the encapsulated mRNA, and blood was collected from the fundus venous plexus after 21 and 35 days, and from the enucleated eyeballs after 49 days. Enzyme-linked immunosorbent assay was employed to measure the titers of antibodies, including virus-neutralizing antibodies. After 49 days, spleens were harvested and assessed for secretion of interferon-gamma (IFN-γ) by solid-phase enzyme-linked immunospot. The results showed successful construction and sequencing of the recombinant plasmid. RNase R digestion confirmed the presence of circular RNAs. Western blotting of the 293T cells transfected with the mRNA showed clear specific bands. The quality of the vaccine was tested by size exclusion chromatography-high performance liquid chromatography, which showed that the purity of the vaccine was about 90%. The mRNA-LNP showcased the particle size of 82.76 nm and an encapsulation rate of approximately 98%. Following three-dose vaccination, all immunized mice exhibited steady weight gain with 100% survival rate throughout the 28-day observation period, indicating no significant acute toxicity associated with the vaccine formulation. The immunized mice showed dose-dependent increases in serum IgG antibody titer and IFN-γ secretion by splenocytes and they were resistant to virus attacks. These findings indicate good immunogenicity and persistence of the pUC57-circ-gD mRNA vaccine, providing a reference for further studies on circRNA vaccines.
Animals ; Mice, Inbred BALB C ; RNA, Circular ; Mice ; Humans ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Antibodies, Viral/blood* ; HEK293 Cells ; Female ; Nanoparticles ; Plasmids

Objective:To compare the feasibility and efficacy of translocator protein (TSPO) molecular probes N, N-diethyl-2-(2-(4- 18F-fluorophenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-FDPA) and 18F-(R)-( N-sec-butyl)-3-fluoromethyl- N-methyl-4-phenylquinoline-2-carboxamide (LW223) for the detection of abdominal vulnerable atherosclerotic plaques (VAP) in rabbit models. Methods:Nine healthy New Zealand white rabbits were divided into group A (control group, n=3), group B (VAP group, n=3) and group C (VAP treatment group, n=3) using completely randomized design. Animals were injected with 18F-FDPA and 18F-LW223 at the end of 12, 16 and 24 weeks. PET/CT and CT angiography (CTA) was performed 40-50 min post injection. All rabbits were sacrificed at the end of 24 weeks after imaging studies. All abdominal aortas were collected for pathological and immunofluorescence examination. Repeated measures analysis of variance (Bonferroni test) and paired t-test were used to analyze the data. Results:Target-to-background ratio (TBR; abdominal aortic lesion/left ventricular blood pool) values of 18F-FDPA in 3 groups at the end of 12, 16 and 24 weeks were significantly different ( F values: 68.09-144.88, all P<0.001). At the end of 12 weeks, there was no increased uptake of 18F-FDPA in the abdominal aorta region in 3 groups. The local 18F-FDPA uptake of the abdominal aorta in group B was significantly higher than the uptake in group C and that in group A at the end of 16 and 24 weeks( P<0.05 or P<0.001), and there were significant differences between group C and group A, with higher uptake in group C (both P<0.01). In 3 groups, there was no significant 18F-LW223 uptake in the abdominal aorta region at 3 time points of PET/CTA imaging. At the end of 12, 16 and 24 weeks, TBR values of 18F-FDPA and 18F-LW223 in 3 groups exhibited statistical differences ( t values: 2.88-36.79, all P<0.05). HE, immunofluorescent CD68 and TSPO staining showed more macrophage infiltration in group B than group C. Conclusion:18F-FDPA can be used to detect VAP in rabbits′ abdominal arteries at early time compared to 18F-LW223, and to evaluate the changes in the stability of vulnerable plaque after lipid-lowering drug intervention.

Objective:To investigate the Kub stage classification of clinical renal tuberculosis and provide a reference for disease evaluation and management.Methods:A retrospective analysis was conducted on clinical data from 180 patients diagnosed with renal tuberculosis who were admitted to the First Affiliated Hospital of Dali University between January 2011 and December 2022. The 180 cases included 82 males and 98 females. The average age was (44.56±9.62) years. The tuberculosis lesions of 101 cases were on left kidney, while that of 79 cases were on right kidney. Localized/multiple lesions were observed in 118 cases, whereas extensive destruction was found in 62 cases. Moreover, the ureters were involved in 165 cases, and bladder invasion occurred in 139 cases. For patients undergoing renal preservation treatment, a comprehensive approach was employed, including ureteral stricture stenting and regular replacement of double-J stent, percutaneous nephrostomy, excision of tuberculosis lesions or partial nephrectomy, ureter reconstruction, and sigmoidocystoplasty. In cases requiring nephrectomy, either laparoscopic or open surgical approaches are utilized. Based on the results of patient imaging and endoscopy, staging and classification were performed based on the extent of tuberculosis lesions involving the kidneys (K), ureters (u), and bladder (b). The state for each above organ was divided into four stages: K stage (K 1-4), u stage (u 0-u 3), and b stage (b 0-b 3), which were then combined with the actual disease condition for further categorization. The classifications included local intrarenal type(K 1-2u 0b 0), local renal-ureteral involvement type(K 1-2u 1-2b 0-2), multiple renal-ureteral invasion type(K 3u 1-3b 0-2) and extensive destruction type(K 4u 1-3b 1-3). Further analysis was conducted on kidney preservation and subsequent disease progression among patients with different subtypes. Results:Among the 180 patients, 15 cases of local intrarenal type underwent kidney-preserving treatment. Out of these cases, 6 patients (4 patients in stage K 1u 0b 0 and 2 patients in stage K 2bu 0b 0) achieved clinical cure after receiving a pure durative anti-tuberculosis for two years. Additionally, 4 patients in stage K 2au 0b 0 attained clinical cure following anti-tuberculosis drugs combined with partial nephrectomy after two years of follow-up. Furthermore, 5 patients in stage K 2bu 0b 0 underwent ureteroscopy and D-J stent placement for regular stent replacement. The stents were subsequently removed after two years, and the patients remained clinically stable. Among the 47 cases with localized renal-ureteral involvement type, all initially underwent kidney-preserving treatment. Of these, 5 patients in stage K 1u 1b 0-2 achieved clinical remission, while disease progression necessitated nephrectomy for 3 patients in stage K 2au 1-2b 0-2 and 7 patients in stage K 2bu 1-2b 0-2. The remaining patients maintained stable conditions. Among the 56 cases of multiple renal-ureteral invasion type, stable conditions were observed in 9 out of 24 patients with stage K 3u 1-2b 0-2, while disease progression necessitated nephrectomy in 15 cases. Nephrectomy was performed for all 32 patients with stage K 3u 3b 0-2. In instances of extensive destruction type, nephrectomy was conducted for all 62 cases. The progression rates of the local renal-ureteral involvement type and the multiple renal-ureteral invasion type were 21.28% (10/47) and 48.39% (15/31), and the difference was statistically significant ( P<0.05). The kidney preservation rates of the local renal-ureteral involvement type and multiple renal-ureteral invasion type were 78.72% (37/47) and 16.07% (9/56), and the difference was statistically significant ( P<0.001). Conclusions:The Kub stage classification can provide reference to management and monitoring for renal tuberculosis. The patients in the local intrarenal type and local renal-ureteral involvement type are often treated with anti-tuberculosis plus ureteral stent implantation or partial nephrectomy or ureteral reconstruction. The patients in the multiple renal-ureteral invasion type and extensive destruction type are mostly managed by nephrectomy.

AIM:To investigate the effect of Cara-gana sinica root(CSR)on ferroptosis in the Erastin-induced chondrocyte ferroptosis model and possi-ble mechanisms.METHODS:The C28/I2 chondro-cyte cell line was cultured to construct a cell model of Erastin-induced ferroptosis.Cell viability was de-tected by MTT assay;cell death was observed by Calcein/PI staining;cell lactate dehydrogenase(LDH)and total glutathione(GSH)levels were de-tected by the kit;reactive oxygen species(ROS)lev-els were detected by fluorescent probe BODIPY 581/591 C11 labeling;mitochondrial membrane po-tential(ΔΨm)changes were observed by Rh123 and JC-1 staining;Western blot was used to detect the expression of ferroptosis-related proteins(AC-SL4,GPX4)and TRPM7 proteins.RESULTS:Erastin treatment decreased chondrocyte viability,in-creased cytotoxicity,induced oxidative stress,dis-rupted ΔΨm,and up-regulated ACSL4 protein ex-pression,while down-regulating GPX4 protein ex-pression and inducing chondrocyte ferroptosis.In contrast,CSR restored cell viability and reduced oxi-dative stress,thereby inhibiting chondrocyte fer-roptosis.In addition,CSR reduced the Erastin-in-duced increase in TRPM7 protein expression level.CONCLUSION:Erastin induced lipid peroxidation in C28/I2 chondrocytes,causing mitochondrial dam-age and ferroptosis;CSR may inhibit chondrocyte ferroptosis by blocking TRPM7,thus exerting a pro-tective effect on chondrocytes.