Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

OBJECTIVE: To investigate the differential efficacy and safety profiles of oral mucosa (OM) grafts compared with acellular dermal matrix (ADM) grafts in the surgical management of long-segment urethral strictures. METHODS: A retrospective cohort study was conducted involving 27 patients who underwent graft urethroplasty for long-segment urethral strictures in Peking University First Hospital, spanning from May 2010 to September 2023. The patient cohort comprised 14 individuals who received OM grafts and 13 who underwent ADM grafts. The participants were stratified into two groups based on the type of grafts material utilized during surgery. The demographic and clinical baseline characteristics included an average age of (43.3±14.0) years in the OM group and (54.2±15.9) years in the ADM group. The mean body mass index (BMI) for the respective groups were (24.7±4.3) kg/m² for OM and (25.4±4.8) kg/m² for ADM. Etiological differences were noted, with idiopathic causes predominantly in the OM cohort and lichen sclerosus in the ADM cohort. RESULTS: The surgical interventions were successfully executed for all the patients. The median stricture length was 4.5 (2.5, 9.0) cm for the OM group and 5.0 (2.0, 14.0) cm for the ADM group (P=0.555). The median operative duration was 160 (71, 221) min for the OM group and 134 (112, 274) min for the ADM group (P=0.065). The catheterization durations was 1.5 (1.0, 6.0) months for the OM group and 3.0 (1.0, 3.0) months for the ADM group. The median postoperative follow-up duration was 12.5 (1.0, 170.0) months for the OM group and 59.0 (3.0, 142.0) months for the ADM group. The surgical success rates were 50.00% in the OM group and 53.85% in the ADM group. No statistically significant differences were observed in postoperative quality of life (QoL) or international prostate symptom score (IPSS) at the final follow-up. The stricture-free survival rates did not differ significantly (HR=0.875, 95%CI: 0.507-1.511, P=0.6). In terms of safety, three patients in the OM group experienced sexual dysfunction, and two had oral complications, whereas the ADM group had one case of postoperative infection. CONCLUSION The findings suggest that ADM grafts are comparable to OM grafts in terms of efficacy and safety for the treatment of long-segment urethral strictures, including complex cases attributed to lichen sclerosus. However, given the small sample size of this study, the above conclusions may have certain limitations. Larger cohort studies will be needed in the future to further validate these findings.
Humans ; Urethral Stricture/surgery* ; Acellular Dermis ; Mouth Mucosa/transplantation* ; Retrospective Studies ; Middle Aged ; Male ; Adult ; Treatment Outcome ; Skin Transplantation/methods* ; Aged

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Objective To investigate the role and underlying mechanism of atorvastatin on hyper-glycemia induced hemorrhagic transformation(HT)in a mouse model of cerebral ischemia.Meth-ods A total of 36 SPF-grade male C57BL/6 mice were randomly divided into sham operation group,HT model group and atorvastatin group,with 12 mice in each group.HE staining was used to observe cerebral hemorrhage,immunofluorescent staining was employed to detect the integrity of blood-brain barrier,and Western blotting was applied to measure the protein expression of IgG,ZO-1,occludin,claduin5,MMP-2 and-9 in ischemic penumbra brain tissues.Results Com-pared with sham operation group,the neurological deficit score,mortality rate,HT incidence,HT grading score,IgG fluorescence intensity,and protein levels of IgG,MMP-2 and-9 were signifi-cantly increased,while the protein levels of ZO-1,occludin and claudin5 were obviously decreased in the HT model group(P＜0.01).Atorvastatin treatment resulted in significantly lower neuro-logical deficit score(2.73±1.19 vs 3.91±0.94),mortality rate(16.7％vs 41.6％),HT incidence(58.3％vs 91.6％),HT grading score(1.00±1.04 vs 2.58±1.13),IgG fluorescence intensity(504.30±105.52 a.u vs 859.91±153.28 a.u),and protein levels of IgG(4.55±1.40 vs 12.06± 3.73),MMP-2(1.87±0.41 vs 2.95±0.68)and-9(1.47±0.24 vs 2.12±0.23)(P＜0.05,P＜0.01),and increased protein levels of ZO-1(1.55±0.20 vs 0.53±0.10),occludin(0.92±0.11 vs 0.35±0.07)and claudin5(0.58±0.04 vs 0.30±0.05)(P＜0.01)when compared with the HT model group.Conclusion Atorvastatin can reduce the permeability of blood-brain barrier by in-hibiting the activation of MMP-2 and MMP-9 and up-regulating the protein levels of ZO-1,occlu-din and claudin5,and thus attenuate hyperglycemia-induced HT.

Pulmonary disease is one of the major threats to human health. However, the current clinical treatment drugs for lung diseases generally have problems such as low lung delivery efficiency, fast clearance rate and obvious toxic side effects. Recently, membrane biomimetic nanocarriers have attracted more and more attention. Due to their advantages of high targeting, long cycle time, good biocompatibility and strong immune escape ability, membrane biomimetic nanocarriers have become a major research hotspot in targeted therapy of lung diseases. In this review, we discuss the main preparation methods of membrane biomimetic nanoparticles, the characteristics of membrane biomimetic nanocarriers from different cell sources and their application in the targeted therapy of lung diseases. At the same time, according to the characteristics of different membranes, the shortcomings, current technical limitations and future prospects are discussed. This review is expected to provide references for the design of membrane biomimetic nanocarriers and their potential applications in the treatment of lung diseases.

Aim To investigate the expression of IncRNA AC079466. 1 in non-small cell lung cancer (NSCLC) tissues and cells, and the effect of its overexpression on the proliferation, apoptosis, migration and invasion of A549 and H1299 cells. Methods Cancer tissues and corresponding adjacent tissues from 20 NSCLC patients were collected, and the expression of IncRNA AC079466. 1 in tissue and cells was detected by qRT-PCR. AC079466. 1 group was transfected with overexpression plasmid, NC group was transfected with empty plasmid, and no transfection was used in the Blank group. MTT, flow cytometry and Transwell were used to detect the effects of IncRNA AC079466. 1 overexpression on the viability, apoptosis, migration and invasion of A549 and HI299 cells. Western blot was used to detect the effect of overexpression of IncRNA AC079466. 1 on the expression of endoplasmic reticulum stress-related factors GRP78, PERK, eIF2a, ATF4, CHOP, Bax and caspase-3. Results Compared with adjacent tissues, the expression of IncRNA AC079466. 1 in cancer tissues significantly decreased. Compared with HBE cells, the expression of IncRNA AC079466. 1 significantly decreased in A549 and H1299 cells. Compared with the Blank group and NC group, the viability, migration and invasion abilities of A549 and H1299 cells in AC079466. 1 group all markedly decreased, the apoptosis rate apparently increased, and the expressions of endoplasmic reticulum stress-related factors GRP78, p-PERK, eIF2a, ATF4, CHOP, Bax and caspase-3 were significantly up-regulated. Conclusion The overexpression of IncRNA AC079466. 1 significantly inhibits the viability, migration and invasion of A549 and HI299 cells, and promotes cell apoptosis. The mechanism may be related to the promotion of endoplasmic reticulum stress-mediated cell apoptosis.

Objective:To investigate the surgical treatment and prognosis of thoracic esophageal squamous cell carcinoma (ESCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 766 patients with thoracic ESCC who were admitted to Sichuan Cancer Hospital & Institute from January 2010 to December 2017 were collected. There were 2 256 males and 510 females, aged (62±8)years. All patients underwent surgical treatment. Observation indicators: (1) treatment; (2) postoperative complications; (3) postoperative survival. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. Result:(1) Treatment. Fifty-two of the 2 766 patients underwent neoadjuvant therapy. There were 1 444 patients undergoing open surgery, including 44 cases conversion to thoracotomy, and there were 1 322 patients undergoing minimally invasive esophagectomy. There were 1 991, 729 and 46 cases with McKeown, Ivor-Lewis and Sweet esophagectomy, respectively. One thousand two hundred and seventy-one of the 2 766 patients underwent postoperative adjuvant therapy. The number of lymph node metastases, the number of lymph node dissected, rate of R 0 resection, operation time of 2 766 patients were 2.1(0,3.0), 22±12, 94.722%(2 620/2 766), (237±66)minutes. (2) Postoperative complications. The overall incidence of postoperative complications was 25.850%(715/2 766). The top two postoperative complications were pneumonia and anastomotic fistula, with incidence rates of 8.604%(238/2766) and 7.484%(207/2766), respectively. One patient may have more than two kinds of postoperative complications. (3) Postoperative survival. The 1-, 3-and 5-year overall survival rates of 2 766 patients were 86.2%, 57.5% and 46.8%, respectively. Further analysis indicated that the 5-year overall survival rates of 510 female patients and 2 256 male patients were 62.0% and 43.3%, respectively, showing a significant difference between them ( χ2=48.94, P<0.05). The 5-year overall survival rates of 693 cases with upper thoracic ESCC, 1 479 cases with middle thoracic ESCC and 594 cases with lower thoracic ESCC were 49.5%, 46.7% and 44.1%, respectively, showing no significant difference among them ( χ2=3.21, P>0.05). The 5-year overall survival rates of 68 cases with stage 0 thoracic ESCC, 259 cases with stage Ⅰ esophageal ESCC, 885 cases with stage Ⅱ thoracic ESCC, 1 222 cases with stage Ⅲ thoracic ESCC, and 332 cases with stage Ⅳ thoracic ESCC were 95.6%, 76.4%, 61.4%, 35.6%, and 14.5%, respectively, showing a significant difference among them ( χ2=500.40, P<0.05). The 5-year overall survival rates of 1 444 patients undergoing open esophagectomy and 1 322 patients undergoing minimally invasive esophagectomy were 42.5% and 51.8%, respectively, showing a significant difference between them ( χ2=31.29, P<0.05). The 5-year overall survival rates of 1 991 cases undergoing McKeown esophagectomy, 729 cases undergoing Ivor-Lewis esophagectomy, and 46 cases undergoing Sweet esophagectomy were 49.5%, 41.2%, and 32.3%, respectively, showing a significant difference among them ( χ2=19.19, P<0.05). Conclusions:Compared with open esophagectomy, minimally invasive esophagectomy brings survival benefits to patients with thoracic esophageal ESCC. Among different esophagectomy methods, the McKeown esophagectomy has also brought survival benefits to patients with esophageal ESCC compared to the Ivor-Lewis esophagectomy and the Sweet esophagectomy.

WS9326A is a peptide antibiotic containing a highly unusual N-methyl-E-2-3-dehydrotyrosine (NMet-Dht) residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by sas16 (P450_Sas) has been shown to be essential for the formation of the alkene moiety in NMet-Dht, but the timing and mechanism of the P450_Sas-mediated α,β-dehydrogenation of Dht remained unclear. Here, we show that the substrate of P450_Sas is the NRPS-associated peptidyl carrier protein (PCP)-bound dipeptide intermediate (Z)-2-pent-1'-enyl-cinnamoyl-Thr-N-Me-Tyr. We demonstrate that P450_Sas-mediated incorporation of the double bond follows N-methylation of the Tyr by the N-methyl transferase domain found within the NRPS, and further that P450_Sas appears to be specific for substrates containing the (Z)-2-pent-1'-enyl-cinnamoyl group. A crystal structure of P450_Sas reveals differences between P450_Sas and other P450s involved in the modification of NRPS-associated substrates, including the substitution of the canonical active site alcohol residue with a phenylalanine (F250), which in turn is critical to P450_Sas activity and WS9326A biosynthesis. Together, our results suggest that P450_Sas catalyses the direct dehydrogenation of the NRPS-bound dipeptide substrate, thus expanding the repertoire of P450 enzymes that can be used to produce biologically active peptides.

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
NF-kappa B/metabolism* ; Interleukin-18/metabolism* ; Proliferating Cell Nuclear Antigen/genetics* ; Cyclin D1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Muscle, Smooth, Vascular ; Cell Proliferation ; Signal Transduction ; Cytokines/metabolism* ; Glucose/metabolism*