Bright Organic Mechanoluminescence and Remarkable Mechanofluorochromism from Circularly Polarized TADF Enantiomers with Aggregation-Induced Emission Properties.

The development of circularly polarized thermally activated delayed fluorescence (CP-TADF) luminogens with stimuli-response characteristics remains challenging. Herein, a pair of organic enantiomers, S-CzTA and R-CzTA, with aggregation-induced emission properties, have been successfully developed by introducing chiral 1,2,3,4-tetrahydronaphthalene and carbazole to phthalimide. They present CP-TADF properties in toluene solutions, giving dissymmetric factors of 0.84×10-3 and -1.03×10-3 , respectively. In the crystalline state, both S-CzTA and R-CzTA can emit intense blue TADF and produce very bright sky-blue mechanoluminescence (ML) and remarkable mechanofluorochromism (MFC) under the stimuli of mechanical force. Single-crystal analysis and theoretical calculation results suggest that their ML activities are probably associated with their chiral and polar molecular structures and unique non-centrosymmetric molecular packing modes. Furthermore, the MFC properties of the enantiomers likely originate from the destruction of crystal structure, leading to the planarization of molecular conformation. This work may provide helpful guidance for developing new CP-TADF materials with force-stimuli-responsive properties.

Overall survival of patients with hepatocellular carcinoma treated with sintilimab and disease outcome after treatment discontinuation.

BACKGROUND: The use of Anti-PD-1 therapy has yielded promising outcomes in hepatocellular carcinoma (HCC). However, limited research has been conducted on the overall survival (OS) of patients with varying tumor responses and treatment duration. METHODS: This retrospective study analyzed HCC patients who received sintilimab between January 2019 and December 2020 at four centers in China. The evaluation of tumor progression was based on Response Evaluation Criteria in Solid Tumors version 1.1. The study investigated the correlation between tumor response and OS, and the impact of drug use on OS following progressive disease (PD). RESULTS: Out of 441 treated patients, 159 patients satisfied the inclusion criteria. Among them, 77 patients with disease control exhibited a significantly longer OS compared to the 82 patients with PD (median OS 26.0 vs. 11.3 months, P < 0.001). Additionally, the OS of patients with objective response (OR) was better than that of patients with stable disease (P = 0.002). Among the 47 patients with PD who continued taking sintilimab, the OS was better than the 35 patients who discontinued treatment (median OS 11.4 vs. 6.9 months, P = 0.042). CONCLUSIONS: In conclusion, the tumor response in HCC patients who received sintilimab affects OS, and patients with PD may benefit from continued use of sintilimab.

A nomogram to predict conversion of laparoscopic surgery to laparotomy for Choledocholithiasis.

BACKGROUND: Laparoscopic surgery is effective for treating common bile duct (CBD) stones. However, it has high requirements for surgeons and the risk of conversion to laparotomy cannot be ignored. However, when conditions during surgery are not favorable, persisting with laparoscopic procedures blindly can lead to serious complications. Our study aimed to establish a nomogram model for predicting conversion of laparoscopic to laparotomy for choledocholithiasis. MATERIALS AND METHODS: A total of 867 patients who were diagnosed with choledocholithiasis and underwent laparoscopic surgery were randomly divided into a training group (70%, n = 607) and a validation group (30%, n = 260). A nomogram was constructed based on the results of logistic regression analysis. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram. RESULTS: Previous upper abdominal surgery, maximum diameter of stone ≥12 mm, medial wall of the duodenum stone, thickening of the gallbladder wall, thickening of CBD wall, stone size/CBD size ≥0.75, and simultaneous laparoscopic hepatectomy were included in the nomogram. The AUC values were 0.813 (95% CI: 0.766-0.861) and 0.804 (95% CI: 0.737-0.871) in the training and validation groups, respectively. The calibration curve showed excellent consistency between the nomogram predictions and actual observations. DCA showed a positive net benefit for the nomogram. CONCLUSIONS: We constructed a nomogram with a good ability to predict conversion to open surgery in laparoscopic surgery for choledocholithiasis, which can help surgeons to make a reasonable operation plan before surgery and timely convert to laparotomy during operation to reduce potential harm to the patient.

Transarterial chemoembolization plus a PD-1 inhibitor with or without lenvatinib for intermediate-stage hepatocellular carcinoma.

AIM: Transarterial chemoembolization (TACE) combined with a PD-1 inhibitor and TACE combined with a PD-1 inhibitor and lenvatinib have recently been reported as promising treatments to improve the prognosis of hepatocellular carcinoma (HCC) patients. This study aims to compare the efficacy of these two treatments. METHODS: A retrospective study was conducted, and patients were recruited from two centers in China. Progression-free survival (PFS) and overall survival (OS) were compared, and the objective response rate (ORR) and disease control rate (DCR) were evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Treatment-related adverse events (AEs) were analyzed to assess safety. RESULTS: The median follow-up for the entire cohort was 11.4 months. Of the 103 patients included in this study, 56 received triple therapy, and 47 received doublet therapy. PFS was significantly higher in the triple therapy group than in the doublet therapy group (mPFS 22.5 vs. 14.0 months, P < 0.001). Similar results were obtained in terms of OS (P = 0.001). The ORR and DCR were also better in the triple therapy group (64.3% vs. 38.3%, P = 0.010; 85.7% vs. 57.4%, P = 0.002). The most common AEs in the triple therapy group were decreased albumin (55.3%), decreased platelet count (51.8%) and hypertension (44.6%). CONCLUSIONS: The combination of TACE with a PD-1 inhibitor and lenvatinib in patients with BCLC stage B HCC might result in significantly improved clinical outcomes with a manageable safety profile compared with TACE with a PD-1 inhibitor.

The application of the spot the difference teaching method in clinical skills training for residents.

BACKGROUND: Clinical skill training (CST) is indispensable for first-year surgical residents. It can usually be carried out through video-based flipped learning (FL) within a web-based learning environment. However, we found that residents lack the process of reflection, blindly imitating results in losing interest and passion for learning in the traditional teaching pattern. The teaching method of "spot the difference" (SDTM), which is based on the fundamentals of the popular game of "spot the difference," is designed to improve students' participation and reflective learning during skill training. This study aimed to evaluate this novel educational model's short-term and long-term effectiveness for surgical residents in China. METHODS: First-year residents who required a three-month rotation in the head and neck surgery department were recruited to participate in a series of CSTs. They were randomized into SDTM and traditional FL (control) groups. Clinical skill performance was assessed with validated clinical skill scoring criteria. Evaluations were conducted by comparing the scores that contain departmental rotation skill examinations and the first China medical licensing examination (CMLE) performance on practical skills. In addition, two-way subjective evaluations were also implemented as a reference for the training results. Training effects were assessed using t tests, Mann-Whitney-Wilcoxon tests, chi-square tests, and Cohen' s effect size (d). The Cohen' s d value was considered to be small (<0.2), medium (0.2-0.8), or large (>0.8). RESULTS: The SDTM group was significantly superior to the control group in terms of after-department skill examination (t=2.179, p<0.05, d=0.5), taking medical history (t=2.665, p<0.05, d=0.59), and CMLE performance on practical skill (t=2.103, p<0.05, d=0.47). The SDTM members rated the curriculum more highly than the control on the items relating to interestingness and participation (p < 0.05) with large effect sizes (d >0.8). There were no significant differences between the two groups on clinical competence (t=0.819, p=0.415, d=0.18), the first-time pass rate for CMLE (χ2 =1.663, p=0.197, d=0.29), and short-term operational skills improvement (t=1.747, p=0.084, d=0.39). CONCLUSIONS: SDTM may be an effective method for enhancing residents' clinical skills, and the effect is significant both short- and long-term. The improvement effect seemed to be more significant in the peer-involved SDTM than training alone. However, despite positive objective results, SDTM still risks student learning burnout. TRIAL REGISTRATION: ISRCTN registry, ISRCTN10598469 , 02/04/2022，retrospectively registered.

Efficient and Color-Tunable Dual-Mode Afterglow from Large-Area and Flexible Polymer-Based Transparent Films for Anti-Counterfeiting and Information Encryption.

It remains a great challenge to develop polymer-based materials with efficient and color-tunable organic afterglow. Two indolocarbazole derivatives IaCzA and IbCzA have been synthesized and doped into poly(vinyl alcohol) (PVA) matrices. It is found that the resulting films can produce unique dual-mode afterglow, which is composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence. Besides, the IbCzA-doped PVA film exhibits intense blue afterglow with Φafterglow and τafterglow up to 19.8 % and 1.81 s, respectively, representing state-of-the-art dual-mode organic afterglow performance. Moreover, our reported film has high flexibility, excellent transparency, and large-area producibility; and the afterglow color of the film can be linearly tuned by temperature. Inspired by these distinctive properties, the PVA doped with IbCzA was employed as temperature-sensitive security ink for anti-counterfeiting and information encryption.

Low genetic diversity in a critically endangered primate: shallow evolutionary history or recent population bottleneck?

BACKGROUND: Current patterns of population genetic variation may have been shaped by long-term evolutionary history and contemporary demographic processes. Understanding the underlying mechanisms that yield those patterns is crucial for informed conservation of endangered species. The critically endangered white-headed langur, Trachypithecus leucocephalus, is endemic to a narrow range in southwest China. This species shows very low genetic diversity in its 2 main relict populations, Fusui and Chongzuo. Whether this has been caused by a short evolutionary history or recent population declines is unknown. Therefore, we investigated the contributions of historical and recent population demographic changes to population genetic diversity by using 15 nuclear microsatellite markers and mitochondrial DNA (mtDNA) control region sequences. RESULTS: Using genetic data from 214 individuals we found a total of 9 mtDNA haplotypes in the Fusui population but only 1 haplotype in the Chongzuo population, and we found an overall low genetic diversity (haplotype and nucleotide diversities: h = 0.486 ± 0.036; π = 0.0028 ± 0.0003). The demographic history inferred from mtDNA and microsatellite markers revealed no evidence for historical population size fluctuations or recent population bottlenecks. Simulations of possible population divergence histories inferred by DIYABC analysis supported a recent divergence of the Chongzuo population from the Fusui population and no population bottlenecks. CONCLUSIONS: Despite severe population declines caused by anthropogenic activities in the last century, the low genetic diversity of the extant white-headed langur populations is most likely primarily due to the species' shallow evolutionary history and to a recent, local population founder event.

Impact of acute kidney injury in donors on renal graft survival: a systematic review and Meta-Analysis.

The acute kidney injury (AKI) of deceased donors was an important strategy to address donor shortage. This meta-analysis was conducted to explore the clinical effect of kidney transplantation from donors with AKI. PubMed, Embase, and Cochrane Library were searched through July 2017. Fourteen cohort studies, involving a total of 15,345 donors, were included. Studies were pooled, and the hazard ratio (HR), relative risk (RR), weighted mean difference (WMD), and their corresponding 95% confidence interval (CI) were calculated. The present meta-analysis showed no significant difference in allograft survival between the AKI and non-AKI groups (HR = 1.16, 95% CI = 0.99-1.37, Pheterogeneity = 0.238, I2 = 21.6%) from 12 months to 120 months after kidney transplantation. However, the time of hospital stay was significantly longer (WMD = 2.49, 95% CI = 1.06-3.92, Pheterogeneity = 0.458, I2 = 0%) and the incidence of delayed graft function (DGF) was significantly higher (RR = 1.76, 95% CI = 1.52-2.04, Pheterogeneity < 0.001, I2 = 71.2%) in the AKI group than in the non-AKI group. We concluded that even though hospital stay time was longer and the incidence of DGF was significantly higher in the AKI group, there is no significant difference in allograft survival between the two groups.

Anisodamine inhibits endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in rhabdomyolysis-induced acute kidney injury.

Anisodamine protects against free radical-induced cellular damage. This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6 J mice, TXNIP-/- and NLRP3 -/- (both were C57BL/6 J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, and interleukin (IL-1α, IL-1ß, and IL-18) were detected. The knock down of TXNIP or NLRP3 expression in mice showed protective effect against RIAKI pathogenesis, as compared with the RIAKI mice. The expression of Caspase-1, ASC, and interleukins, renal injury, renal tubular cells apoptosis in TXNIP-KD and LNPR3-KD mice were significantly inhibited in comparison with the RIAKI mice. Moreover, anisodamine treatment reduced expression of ER stress markers IRE-1α, CHOP, and ATF4, TXNIP and NLRP3, as well as ACS, Caspase-1, IL-1α, IL-1ß, and IL-18, showing moderate protective effect on the changes of above factors comparing with TXNIP or NLRP3 knock down. This study declared that anisodamine showed protective effect on RIAKI model may by inhibiting ER stress associated TXNIP/NLRP3 inflammasome.

Kidney transplantation from donors with rhabdomyolysis and acute renal failure.

Rhabdomyolysis in deceased donors usually causes acute renal failure (ARF), which may be considered a contraindication for kidney transplantation. From January 2012 to December 2016, 30 kidneys from 15 deceased donors with severe rhabdomyolysis and ARF were accepted for transplantation at our center. The peak serum creatinine (SCr) kinase, myoglobin, and SCr of the these donors were 15 569±8597 U/L, 37 092±42 100 µg/L, and 422±167 µmol/L, respectively. Two donors received continuous renal replacement therapy due to anuria. Six kidneys exhibited a discolored appearance (from brown to glossy black) due to myoglobin casts. The kidney transplant results from the donors with rhabdomyolysis donors were compared with those of 90 renal grafts from standard criteria donors (SCD). The estimated glomerular filtration rate at 2 years was similar between kidney transplants from donors with rhabdomyolysis and SCD (70.3±14.6 mL/min/1.73 m2 vs 72.3±15.1 mL/min/1.73 m2 ). We conclude that excellent graft function can be achieved from kidneys donors with ARF caused by rhabdomyolysis.

Improvement of lincomycin production by mutant selection and metabolic regulation.

Lincomycin is a lincosamide antibiotic produced by Streptomyces lincolnensis. Through mutagenesis by ethylmethansulfonate (EMS) and ultraviolet (UV) irradiation repeatedly, M2 was picked out in plate with glutamine and propylproline orderly. In 50-L stirred bioreactor, the production of lincomycin, fermented by M2, was increased to 8136 u/ml under the optimal condition as compared to original strain S. lincolnensis 07-5 (6634 u/ml). Two-dimensional gel electrophoresis (2-D GE) and mass spectrometry (MS)-shown LmbG, LmbI, and acetohydroxy acid isomeroreductase were remarkably synthesized in M2. The gene lmbG and lmbI are responsible for methylation in the lincomycin biosynthetic cluster, while acetohydroxy acid isomeroreductase contributes to stronger metabolic capability. Finally, we obtained a better strain for industrial production.

Newly identified thermostable esterase from Sulfobacillus acidophilus: properties and performance in phthalate ester degradation.

EstS1, a newly identified thermostable esterase from Sulfobacillus acidophilus DSM10332, was heterologously expressed in Escherichia coli and shown to enzymatically degrade phthalate esters (PAEs) to their corresponding monoalkyl PAEs. The optimal pH and temperature of the esterase were found to be 8.0 and 70°C, respectively. The half-life of EstS1 at 60°C was 15 h, indicating that the enzyme had good thermostability. The specificity constant (kcat/Km) of the enzyme for p-nitrophenyl butyrate was as high as 6,770 mM(-1) s(-1). The potential value of EstS1 was demonstrated by its ability to effectively hydrolyze 35 to 82% of PAEs (10 mM) within 2 min at 37°C, with all substrates being completely degraded within 24 h. At 60°C, the time required for complete hydrolysis of most PAEs was reduced by half. To our knowledge, this enzyme is a new esterase identified from thermophiles that is able to degrade various PAEs at high temperatures.

[Repairing partial suprahyoid epiglottis-preserved circumferential defect in near total laryngectomy with anterior medial thigh flap in advanced laryngeal cancer].

Objective: To explore the feasibility to restore pronunciation function by repairing partial suprahyoid epiglottis-preserved circumferential defect in near total laryngectomy with anterior medial thigh flap in advanced laryngeal cancer. Methods: A retrospective study of 5 male patients with advanced laryngeal cancer between August 2019 and October 2022, aged 56-73 years, with an average age of 65 years were reviewed. The disease duration ranged from 3 to 24 months, with an average of 8 months. Tumor classification by location: 2 cases of glottic type, 2 cases of supraglottic type, and 1 case of subglottic type; TNM staging: 3 cases of T 4N 0M 0 stage, 1 case of T 4N 1M 0 stage, and 1 case of T 4N 2M 0 stage; American Joint Committee on Cancer (AJCC) staging (2017): stage Ⅳ. Near total laryngectomy with partial suprahyoid epiglottis-preserved and selective bilateral neck dissection were performed before the anterior medial thigh flap was used to repair the circumferential defects. The flap size ranged from 6 cm×5 cm to 8 cm×6 cm. Four patients underwent adjuvant radiotherapy and chemotherapy after operation, while 1 patient did not receive any other adjuvant treatment such as radiochemotherapy. Results: The flaps of all 5 patients survived without obvious neck infection. One patient developed a slight pharyngeal fistula after oral feeding at 1 month after operation, which healed after another week of gastric feeding. Primary healing also achieved in the thigh donor area. One patient had bilateral cervical lymph node metastasis, and 1 patient had lymph node metastasis on one side. The remaining 3 patients had no cervical nodes metastasis on both sides. All 5 patients were followed up 12-36 months, with an average of 27.6 months. Four patients had clear, audible, and hoarse voice while 1 patient (case 3) had pronunciation similar to whispering. Laryngoscopy showed that the reconstructed laryngeal inlet was fissure-shape and the reconstructed laryngo-trachea canal below the laryngeal inlet was gradually enlarged. At 1 month after operation, the gastric tube was withdrawn and the food was taken orally. There was no obvious aspiration pneumonia. The tracheostomy tube could be blocked in 4 patients for from 30 seconds to 3 minutes. Among them, 3 patients were able to make a noticeable pronunciation even when the tube was not blocked, and they were able to engage in barrier-free language communication; the tracheostomy tube could not be blocked in 1 patient who had a pronunciation similar to whispering. Preliminary voice analysis showed that the patients have a relaxed and natural pronunciation, without obvious breath-holding or air-swallowing movement, compared to patients with esophageal pronunciation. Decannulation did not achieved until the last follow-up in all 5 patients. Conclusion: The anterior medial thigh flap can repair circumferential defects after near total laryngectomy in advanced laryngeal cancer patients and achieve satisfactory pronunciation, thus can serve as an effective pronunciation rehabilitation method. The preserved part of epiglottis may play a role to prevent postoperative aspiration.

Model-Based Reinforcement Learning With Isolated Imaginations.

World models learn the consequences of actions in vision-based interactive systems. However, in practical scenarios like autonomous driving, noncontrollable dynamics that are independent or sparsely dependent on action signals often exist, making it challenging to learn effective world models. To address this issue, we propose Iso-Dream++, a model-based reinforcement learning approach that has two main contributions. First, we optimize the inverse dynamics to encourage the world model to isolate controllable state transitions from the mixed spatiotemporal variations of the environment. Second, we perform policy optimization based on the decoupled latent imaginations, where we roll out noncontrollable states into the future and adaptively associate them with the current controllable state. This enables long-horizon visuomotor control tasks to benefit from isolating mixed dynamics sources in the wild, such as self-driving cars that can anticipate the movement of other vehicles, thereby avoiding potential risks. On top of our previous work (Pan et al. 2022), we further consider the sparse dependencies between controllable and noncontrollable states, address the training collapse problem of state decoupling, and validate our approach in transfer learning setups. Our empirical study demonstrates that Iso-Dream++ outperforms existing reinforcement learning models significantly on CARLA and DeepMind Control.

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab versus Transarterial Chemoembolization Alone in Intermediate-stage Hepatocellular Carcinoma: A Multicenter Retrospective Study.

Purpose: Combining transarterial chemoembolization (TACE) with systemic therapy has shown significant efficacy for intermediate-stage hepatocellular carcinoma (HCC) patients. This study aimed to validate the therapeutic efficacy of TACE combined with atezolizumab and bevacizumab (TACE + Atez/Bev) compared to TACE alone. Methods: A retrospective study was conducted across three centers in China, encompassing 155 patients at the intermediate-stage of HCC. Propensity Score Matching (PSM) was used to minimize selection bias, with a ratio of 1:1. Primary outcomes were TACE-specific Progression-Free Survival (PFS) and Overall Survival (OS). Objective Response Rate (ORR) and Disease Control Rate (DCR) were assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events (AEs) related to treatment were analyzed to evaluate safety. Results: Before PSM, the TACE + Atez/Bev group demonstrated extended median OS (not reached vs 20.3 months, P = 0.004) and PFS (20.0 months vs 9.8 months, P = 0.029) compared to the TACE-alone group. The TACE + Atez/Bev group also had a higher ORR (60.9% vs 41.3%, P = 0.026) and DCR (89.1% vs 58.7%, P < 0.001) than the TACE-alone group. After applying the PSM, the study included 42 pairs of patients. Compared to the TACE-alone group, the combination therapy group also showed significantly longer median OS (not reached vs 21.4 months, P = 0.008) and PFS (21.7 vs 9.7 months, P = 0.009). The combination therapy group also had a higher ORR (66.7% vs 38.1%, P = 0.009) and DCR (92.9% vs 57.1%, P < 0.001). AEs in the combination therapy group were mostly manageable, with the most common being elevated liver transaminase. Conclusion: In treating intermediate-stage HCC, the survival benefit of combining TACE with atezolizumab and bevacizumab was significantly higher than TACE alone, and the treatment was well-tolerated.

Prognostic Analysis of Lymphovascular Invasion in Stages I-III Colorectal Cancer: A Retrospective Study Based on Propensity Score Match.

INTRODUCTION: Lymphovascular invasion (LVI) is a micropathological tumor factor believed to increase the risk of tumor metastasis and spread. Propensity score matching (PSM) is a statistical method that can control confounding factors. Current research rarely considers the confounding relationship between LVI and other factors that may influence prognosis. This study aimed to investigate the relationship between LVI and prognosis in patients with stage I-III colorectal cancer (CRC) by using propensity score matching (PSM). METHODS: This was a retrospective study involving 610 patients. PSM was used to adjust for baseline differences between the groups. The survival rates were calculated. A nomogram was constructed based on the Cox proportional hazards model before matching. The C-index, receiver operating characteristic curve (ROC), and calibration curve were used to evaluate the nomogram. RESULTS: A total of 150 patients tested positive for LVI, accounting for 24.6% of the total, and 120 couples of patients were identified after PSM. The survival curve and Cox proportional hazards model after matching confirmed the adverse effects of LVI on tumor prognosis. The Cox proportional hazards model before matching showed that age, carcinoembryonic antigen level, T stage, N stage, histologic grade and LVI were independent prognostic factors. The C-index of the nomogram established based on the Cox proportional hazards model was 0.787 (95% CI=0.728-0.845). The areas under the curve were 0.796 in the 3-year ROC. CONCLUSIONS: LVI is an adverse prognostic factor in patients with stage I-III colorectal cancer.

[Application of transverse cervical artery flap in laryngeal function preservation surgery of hypopharyngeal carcinoma].

Objective: To explore the value and limitation of transverse cervical artery flap in laryngeal function preservation surgery of hypopharyngeal carcinoma. Methods: Between January 2013 and December 2019, 18 male patients with hypopharyngeal carcinoma were admitted. The patients' age ranged from 48 to 77 years, with a median age of 65 years. The disease duration ranged from 3 to 8 months (mean, 5 months). All patients were diagnosed as squamous cell carcinoma by biopsy before operation. According to the American Joint Committee on Cancer (AJCC) guidelines (2017, 8th ed), TNM staging was T2N0M0 in 9 cases, T2N1M0 in 2 cases, and T3N0M0 in 7 cases, and cTNM staging was stage Ⅱ in 9 cases and stage Ⅲ in 9 cases. The lesions of 15 cases were located in the piriform fossa of hypopharynx on one side, among which the esophageal entrance was involved in 4 cases. The lesions of 3 cases were located in the posterior wall of the hypopharynx with esophageal entrance involvement. After partial pharyngo- laryngectomy and bilateral neck lymph node dissection, the hypopharyngeal and laryngeal defects were repaired with transverse cervical artery flaps, the size of the flap ranged from 4 cm×3 cm to 6 cm×4 cm. The accompanying vein of transverse cervical artery (7 cases), external jugular vein (6 cases), and combination of both (5 cases) served as venous reflux. Retrograde external jugular venous reflux exercise was performed in 2 flaps with venous reflux obstruction during operation. The incisions at donor sites were directly sutured or via relaxed incision sutured. Radiotherapy and chemotherapy were supplemented within 3 months after operation. Tracheal cannula with air bag was used to prevent patients from aspiration in the early postoperative stage. Results: The operation time was 4-6 hours, with an average of 4.5 hours. All patients were followed up 1-5 years (mean, 2 years and 6 months). Postoperative pathological examination showed that 7 cases had cervical lymph node metastases on the affected side, and there was no lymph node metastasis in cervical region Ⅴ; the remaining 11 cases had no lymph node metastasis. After operation, 16 flaps survived successfully, and 2 flaps with external jugular vein reflux were covered with white pseudomembrane, no flap necrosis was found after the pseudomembrane fell off. Four cases had no obvious accidental aspiration after operation; 14 cases had obvious accidental aspiration, of which 13 cases were significantly reduced at 3 months after operation, and 1 case still had obvious accidental aspiration at 6 months after operation, and the accidental aspiration decreased significantly after pulling out the gastric tube. All patients had no aspiration pneumonia. One case developed upper mediastinal lymph node metastasis at 1 year and 2 months after operation, and died of recurrence and pulmonary infection at 1 year and 3 months after operation. No recurrence or metastasis was found in the remaining 17 cases during follow-up. Tracheal cannula was successfully removed in 7 cases at 2-5 months after operation. Different degrees of accidental aspiration in 11 patients were confirmed by esophagography, so the tracheal cannula was retained. All patients had pronunciation function after operation. All incisions at the donor sites healed by first intention, and the shoulder joint function was normal. Conclusion: Using transverse cervical artery flap to repair the hypopharyngeal and laryngeal defects during hypopharyngeal carcinoma surgery in patients without lymph node metastasis in cervical region Ⅴ, can achieve good results of laryngeal function preservation. In cases with suspected lymph node metastasis in cervical region Ⅴ or venous dysplasia of accompanying vein of transverse cervical artery, there is a risk of tumor recurrence or flap necrosis, and the repair method needs to be cautiously employed.

Environmental DNA captures native and non-native fish community variations across the lentic and lotic systems of a megacity.

Globally, urbanization poses a major threat to terrestrial biodiversity, yet its impact on fish diversity is poorly understood, mainly because of surveying difficulties. In this study, environmental DNA metabarcoding was used to survey fish communities at 109 lentic and lotic sites across Beijing, and how environmental variables affect fish biodiversity at fine urban spatial scales was investigated. We identified 52 native and 23 non-native taxa, with lentic and lotic waters harboring both common and habitat-specific species. Water quality strongly affected native fish diversity, especially in lentic systems, but had little influence on non-native diversity. Fish diversity showed little response to urban land cover variation, but the relative sequence abundance of non-natives in lotic waters increased linearly with distance from the city center. Our findings illustrate the complex effects of urbanization on native versus non-native fishes in different aquatic habitats and highlight the distinctive considerations needed to conserve urban aquatic biodiversity.

A novel classification in predicting prognosis and guiding postoperative management after R0 liver resection for patients with hepatocellular carcinoma and microvascular invasion.

BACKGROUND: Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). The current classification of MVI is not refined enough to prognosticate long-term survival of these patients, and a new MVI classification is needed. METHODS: Patients with HCC who underwent R0 LR at the Eastern Hepatobiliary Surgery Hospital from January 2013 to December 2013 and with resected specimens showing MVI were included in this study with an aim to establish a novel MVI classification. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: There were 180 patients in the derivation cohort and 131 patients in the external validation cohort. The following factors were used for scoring: α-fetoprotein level (AFP), liver cirrhosis, tumor number, tumor diameter, MVI number, and distance between MVI and HCC. Three classes of patients could be distinguished by using the total score: class A, ≤3 points; class B, 3.5-5 points and class C, >5 points with distinct long-term survival outcomes (median recurrence free survival (mRFS), 22.6, 10.2, and 1.9 months, P < 0.001). The predictive accuracy of this classification was more accurate than the other commonly used classifications for HCC patients with MVI. In addition, the mRFS of class C patients was significantly prolonged (1.9 months vs. 6.2 months, P < 0.001) after adjuvant transcatheter arterial chemoembolization (TACE). CONCLUSIONS: A novel MVI classification was established in predicting prognosis of HCC patients with MVI after R0 LR. Adjuvant TACE was useful for class C patients.

Effects of Stereotactic Body Radiation Therapy Plus PD-1 Inhibitors for Patients With Transarterial Chemoembolization Refractory.

Background and Aims: Patients with intermediate-stage hepatocellular carcinoma (HCC) who are refractory to transarterial chemoembolization (TACE) have a poor prognosis. This study aimed to explore whether stereotactic body radiation therapy (SBRT) combined with PD-1 inhibitors could improve the clinical outcomes of such patients. Methods: This retrospective cohort study included patients with intermediate-stage HCC who were diagnosed with TACE refractoriness between January 2019 and December 2020 in the Eastern Hepatobiliary Surgery Hospital and the First Affiliated Hospital of Wenzhou Medical University. The patients were divided into two groups: (1) those who switched from TACE to receive stereotactic body radiotherapy (SBRT) combined with PD-1 inhibitors; (2) those who continued TACE treatment and added PD-1 inhibitors. Progression-free survival (PFS), overall survival (OS), and tumour response were assessed in both groups after becoming refractory to TACE treatment. Results: Of the seventy-six patients included in this study, the median PFS was 19.6 months in the SBRT-IO group (n=31) and 10.1 months in the TACE-IO group (n=45, p<0.05). The SBRT-IO group also had a significantly higher OS than the TACE-IO group (p<0.05). The objective response rate (ORR) and disease control rate (DCR) were also better in the SBRT-IO group (ORR, 71.0% vs. 15.6%, OR=8.483, 95% CI 3.319-21.680, P < 0.001; DCR, 80.6% vs. 31.1%, OR=9.226, 95% CI 3.096-27.493, P < 0.001). Conclusions: SBRT combined with a PD-1 inhibitor improves PFS and OS in TACE-refractory patients with intermediate-stage HCC. Therefore, this therapy is a suitable option in cases of TACE treatment failure.