Outcomes of a Double-Cup Construct to Treat Paprosky 3A and 3B Acetabular Defects at a Mean of 39 Months.

BACKGROUND: Modular reconstruction systems based on porous tantalum (PT) prosthetic components have been increasingly used for the treatment of complex acetabular bone defects in revision total hip arthroplasty. We report a novel technique that applies a revision cup as a "super-augment" to form a "double-cup" construct for Paprosky type III defects. METHODS: A retrospective review was conducted on revision total hip arthroplasty cases, comparing those treated with double-cup constructs (DC group, n = 48) to those treated with PT shells and augments (PT group, n = 48). All procedures were performed at the same institute between 2017 and 2022. Clinical outcome evaluation utilized the Harris Hip Score, Oxford Hip Score, and the 36-Item Short Form Survey. Preoperative and postoperative radiographic assessments measured hip center of rotation (COR) position and leg length discrepancy. Additionally, postoperative complications and implant survivorship were monitored during the follow-up period. RESULTS: The clinical outcomes improved substantially in both groups, which showed no significant difference in the Harris Hip Score (P = .786), the Oxford Hip Score (P = .570), and the 36-Item Short Form Survey (P = .691). Compared to the PT group, the reconstruction COR was significantly closer to the anatomic COR (vertical distance: 2.630 versus 7.355 mm, P = .0034; horizontal distance: 1.881 versus -6.413 mm, P < .0001) in Paprosky 3B type defects. Additionally, postoperative leg length discrepancy was less in the DC group (-8.252 versus -1.821 mm, P = .0008). Dislocation was the main complication in the DC group, and only 1 patient received re-revision due to repeated dislocation. The cumulative survival rate of the DC group (100%; 95% confidence interval 100) was better than the PT group (83.4%; 95% confidence interval 70.5 to 98.6) when re-revisions for aseptic loosening were the endpoint (P = .046). CONCLUSIONS: The DC is a reliable revision technique for the reconstruction of Paprosky type III bone defects. Although dislocation remains challenging, the biomechanically superior restoration achieved by this technique lowers the risk of aseptic loosening.

Enantioselective Synthesis of Cyclobutane Derivatives via Cascade Asymmetric Allylic Etherification/[2 + 2] Photocycloaddition.

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.

Glutathione catabolism by Enterobacteriaceae species to hydrogen sulphide adversely affects the viability of host systems in the presence of 5'fluorodeoxyuridine.

Reduced glutathione (GSH) plays an essential role in relieving oxidative insult from the generation of free radicals via normal physiological processes. However, GSH can be exploited by bacteria as a signalling molecule for the regulation of virulence. We describe findings arising from a serendipitous observation that when GSH and Escherichia coli were incubated with 5'fluorodeoxyuridine (FUdR)-synchronised populations of Caenorhabditis elegans, the nematodes underwent rapid death. Death was mediated by the production of hydrogen sulphide mainly through the action of tnaA, a tryptophanase-encoding gene in E. coli. Other Enterobacteriaceae species possess similar cysteine desulfhydrases that can catabolise l-cysteine-containing compounds to hydrogen sulphide and mediate nematode killing when worms had been pre-treated with FUdR. When colonic epithelial cell lines were infected, hydrogen sulphide produced by these bacteria in the presence of GSH was also able to inhibit ATP synthesis in these cells particularly when cells had been treated with FUdR. Therefore, bacterial production of hydrogen sulphide could act in concert with a commonly used genotoxic cancer drug to exert host cell impairment. Hydrogen sulphide also increases bacterial adhesion to the intestinal cells. These findings could have implications for patients undergoing chemotherapy using FUdR analogues that could result in intestinal damage.

Apolipoprotein A-1 protected hepatic ischaemia-reperfusion injury through suppressing macrophage pyroptosis via TLR4-NF-κB pathway.

BACKGROUND AND AIMS: Apolipoprotein A-1 (ApoA-1), the major apolipoprotein of high-density lipoprotein, plays anti-atherogenic role in cardiovascular diseases and exerts anti-inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA-1 in hepatic ischaemia-reperfusion (I/R) injury is unknown. METHODS: In this study, we measured ApoA-1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA-1 knockout mice, ApoA-1 mimetic peptide D-4F treatment mice and corresponding control mice to examine the effect of ApoA-1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study. RESULTS: The results showed that ApoA-1 expression was down-regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA-1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA-1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA-1 deficiency. Furthermore, the up-regulated pyroptosis process was testified to be mediated by ApoA-1 through TLR4-NF-κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D-4F ameliorated hepatic I/R injury. CONCLUSIONS: Our study has identified the protective role of ApoA-1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4-NF-κB pathway. The effect of ApoA-1 may provide a novel therapeutic approach for hepatic I/R injury.

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages.

ABSTRACT: Salidroside has anti-inflammatory and antiatherosclerotic effects, and mitochondrial homeostasis imbalance is closely related to cardiovascular disease. The aim of this study was to investigate the effect of salidroside on mitochondrial homeostasis after macrophage polarization and elucidate its possible mechanism against atherosclerosis. RAW264.7 cells were stimulated with 1 µg·mL -1 Lipopolysaccharide and 50 ng·mL -1 IFN-γ establish M1 polarization and were also pretreated with 400 µM salidroside. The relative expression of proinflammatory genes was detected by RT-PCR whereas that of mitochondrial homeostasis-related proteins and nuclear factor kappa-B (NF-κB) was detected by WB. Levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and mass were measured by chemifluorescence whereas that of NF-κB nuclear translocation was detected by immunofluorescence. Compared with the Mφ group, the M1 group demonstrated increased mRNA expression of interleukin-1ß , inductible nitric oxide synthase (iNOS), and tumor necrosis factor-α ; increased protein expression of iNOS, NOD-like receptor protein 3, putative kinase 1 , and NF-κB p65 but decreased protein expression of MFN2, Tom20, and PGC-1α; decreased mitochondrial membrane potential and mass; and increased ROS levels and NF-κB p65 nuclear translocation. Salidroside intervention decreased mRNA expression of interleukin-1ß and tumor necrosis factor-α compared with the M1 group but did not affect that of iNOS. Furthermore, salidroside intervention prevented the changes in protein expression, mitochondrial membrane potential and mass, ROS levels, and NF-κB p65 nuclear translocation observed in the M1 group. In summary, salidroside ultimately inhibits M1 macrophage polarization and maintains mitochondrial homeostasis after macrophage polarization by increasing mitochondrial membrane potential, decreasing ROS levels, inhibiting NF-κB activation, and in turn regulating the expression of proinflammatory factors and mitochondrial homeostasis-associated proteins.

Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma.

BACKGROUND AND AIMS: In recent years, more and more inflammatory indicators have been studied to predict the long-term survival of patients with ampullary carcinoma (AC) after radical resection, but these prognostic indicators are still controversial. Therefore, based on previous inflammation scores, this study established a novel, easily accessible, more feasible and more predictive prognostic marker [Carbohydrate antigen199 to gamma-glutamyltransferase ratio (CA19-9/GGT)] to better assess the prognostic significance in AC patients undergoing radical resection. METHODS: Overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox regression model. Correlation between CA19-9/GGT and clinicopathological variables were analyzed by Chi-squared test, Fisher ' s exact test, independent sample t test and Mann-Whitney U test. The performance of prognostic indexes is compared by the consistency index (C-index). The prediction accuracy of nomogram is further confirmed by calibration curve and decision curve analysis (DCA). RESULTS: CA19-9/GGT was an independent risk factor affecting OS [P = 0.001, hazard ratio (HR) 2.459, 95% confidence intervals (CI) 1.450-4.167] and RFS (P = 0.002, HR 2.333, 95% CI 1.371-3.971) in multivariate analysis. The optimal cut-off value of CA19-9/GGT was 0.14. In CA19-9/GGT correlation analysis, high risk group (> 0.14) was significantly associated with poor prognosis. The predictive performance of CA19-9/GGT (OS: C-index = 0.753, RFS: C-index = 0.745) was confirmed to be superior to other prognostic indicators according to the C-index. Compared with the simple AJCC staging system, the Nomogram prediction model (OS: C-index = 0.787, RFS: C-index = 0.795) established by the combination of CA19-9/GGT and AJCC 8th TNM staging system has higher prediction accuracy. CONCLUSIONS: CA19-9/GGT was an independent prognostic indicator after radical resection of AC. Incorporating CA19-9/GGT into the AJCC TNM staging system optimized the prediction accuracy of the TNM staging system, and further verified the predictive value of CA19-9/GGT.

Dysregulation of MiR-199a/IL8 pathway in chronic Cr (VI)-induced tumor growth and angiogenesis.

Hexavalent chromium [Cr(VI)] is a well-known environmental carcinogen. Recent studies revealed that chronic exposure of human bronchial epithelial cells (BEAS-2B, B2B) to Cr(VI) activated several signaling pathways and induced cell malignant transformation and tumor growth. However, new mechanisms of Cr(VI) in inducing carcinogenesis remains to be elucidated. This study showed that miR-199a expression levels were significantly lower in Cr(VI)-transformed Cr-T cells. By using the mouse model, the expression levels of miR-199a were significantly decreased in blood samples and lung tissues of mice intranasally exposed to Cr(VI) for 12 weeks compared to the solvent exposure control. Overexpression of miR-199a inhibited tube formation and angiogenesis. C-X-C motif chemokine ligand 8 (CXCL8, IL8) levels were significantly higher in blood samples of Cr (VI)-exposed workers compared to normal workers, and forced expression of miR-199a in the cells suppressed IL8 levels. miR-199a suppression induced expression of hypoxia-inducible factor 1α (HIF-1α) and nuclear factor kappa B (NF-κB) p65 to increase IL8 expression. With animal experiment, the results showed that miR-199a overexpression inhibited tumor growth and angiogenesis through inhibiting IL8, HIF-1α and NF-κB p65 expression in vivo. These results show that miR-199a/IL8 pathway is important in Cr(VI)-induced carcinogenesis and angiogenesis.

LncRNA FIRRE stimulates PTBP1-induced Smurf2 decay, stabilizes B-cell receptor, and promotes the development of diffuse large B-cell lymphoma.

Sustained expression of B-cell receptor (BCR) critically contributes to the development of diffuse large B-cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull-down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull-down, and mRNA stability assays. Smurf2-mediated BCR ubiquitination was investigated using co-immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up-regulated in and essentially maintained multiple malignant behaviors of BCR-dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE-PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.

Reconstruction of upper mediastinal pleura reduces postoperative complications in enhanced recovery surgery system after esophagectomy: A propensity score matching study.

OBJECTIVES: This study aimed to explore the effect of suturing upper mediastinum pleura on postoperative complications, surgery-related mortality, and hospital stay. METHODS: Four hundred and thirty-eight patients with esophageal cancer who underwent esophagectomy were identified. Patients were divided into two groups: those in the test group who received reconstruction of upper mediastinal pleura, those in the conventional group who did not. The incidence of postoperative complications, surgery-related mortality, and hospital stay were compared. To reduce the impact of confounding factors, a propensity score matching (PSM) method was performed. RESULTS: A total of 273 patients were treated with suturing upper mediastinal pleura and 165 were not. After PSM, compared with the conventional group, the incidence of atelectasis (7.2% vs. 1.4%, p = 0.035), anastomotic leakage (5.8% vs. 0.7%, p = 0.036), and delayed gastric emptying (10.8% vs. 3.6%, p = 0.034) were significantly lower in the test group. And suturing the upper mediastinal pleura could reduce the severity of leakage (p = 0.045), consistent with the results before PSM. Moreover, there were no significant differences in the incidence of other complications, postoperative hospital stay, and 30-day mortality (all p > 0.05). CONCLUSIONS: In this study, suturing the upper mediastinal pleura can reduce the incidence of atelectasis, anastomotic leakage, and delayed gastric emptying, and the severity of leakage, without increasing the incidence of other complications, surgery-related death, and postoperative hospital stay.

Synthesis and antidepressant activity of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives selectively targeting SSRI/5-HT1A.

A series of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives were synthesized and evaluated for the serotonin reuptake inhibitory abilities and binding affinities to the 5-HT1A receptor. The metabolic stabilities of these compounds were measured in vitro using human or mouse liver microsomes and the antidepressant activities were explored In vivo using the forced swimming test (FST) and tail suspension test (TST) in mice. The results indicated that the compound 12a exhibited strongest serotonin reuptake inhibition (IC50 = 8.2 nM) and marked 5-HT1A receptor affinity (Ki = 0.069 nM), which were significantly superior to lead compounds Ⅰ and Ⅱ. Meanwhile, compound 12a showed good metabolic stability in vitro and exhibited potential antidepressant-like effects in the FST and TST in mice.

Iridium-Catalyzed Asymmetric Allylic Benzylation with Photogenerated Hydroxy-o-Quinodimethanes.

An iridium-catalyzed asymmetric allylic benzylation of aryl vinyl carbinols under light irradiation is described. 2-Methylbenzophenone derivatives are employed and activated to hydroxy-o-quinodimethanes by an ultraviolet (UV) light. This approach enables asymmetric allylic benzylation with high enantioselectivity (up to 99 % ee) from readily available 2-methylbenzophenones without the utilization of strong bases, and pre-activation or pre-functionalization of the substrates. Moreover, deuterium experiments reveal the generation of nucleophilic benzyl species from 2-methylbenzophenone under UV irradiation.

Iodination/Amidation of the N-Alkyl (Iso)quinolinium Salts.

The NaIO4-mediated sequential iodination/amidation reaction of N-alkyl quinolinium iodide salts has been first developed. This cascade process provides an efficient way to rapidly synthesize 3-iodo-N-alkyl quinolinones with high regioselectivity and good functional group tolerance. This protocol was also amenable to the isoquinolinium salts, thus providing a complementary method for preparing the 4-iodo-N-alkyl isoquinolinones.

Synthesis and biological evaluation of novel antipsychotic trans-4-(2-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)ethyl)cyclohexan-1-amine derivatives targeting dopamine/serotonin receptor subtypes.

In this study, a series of trans-4-(2-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)ethyl)cyclohexan-1-amine derivatives as potential antipsychotics were synthesized and biologically evaluated to discover potential antipsychotics with good drug target selectivity. The preliminary structure-activity relationship was discussed, and optimal compound 12a showed both nanomolar affinity for D2/D3/5-HT1A/5-HT2A receptors and weak α1 and H1 receptor binding affinity. In addition, 12a was metabolically stable in vitro, displayed micromolar affinity for the hERG channel, and exhibited antipsychotic efficacy in the animal model of locomotor-stimulating effects of phencyclidine.

Debridement, Antibiotics, and Implant Retention in Periprosthetic Joint Infection: What Predicts Success or Failure?

BACKGROUND: Debridement, antibiotics and implant retention (DAIR) is the treatment of choice for acute postoperative and acute hematogenous periprosthetic joint infection (PJI). There is limited literature on predictive prognostic factors for DAIR. We aim to report the outcomes of DAIR and investigate the predictive prognostic factors. METHODS: We retrospectively reviewed 106 DAIRs. Failure was defined as requiring removal of TKA implants. Predictive factors that may influence success of DAIR treatment such as age, gender, body mass index, ethnicity, American Society of Anesthesiologists score, comorbidities, preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein, symptom duration, time between total knee arthroplasty and DAIR, cultures, rifampicin use, polyethylene liner change, and antibiotic duration were analyzed. RESULTS: The success rate of DAIR was 69.8% (74/106 patients). For successes, mean time from DAIR-to-mortality was longer than failures (61.6 ± 42.7 vs 9.75 ± 9.60 months, P = .0150). Methicillin-susceptible Staphylococcus aureus PJI (odds ratio [OR] 3.64, confidence interval [CI] 1.30-10.2, P = .0140) was a significant predictor for failure of DAIR. Higher preoperative ESR correlated to failure (OR 1.02, CI 1.01-1.04, P = .008). In successes, mean ESR was 75.4 (66.1-84.6), whereas mean ESR in failures was 116 (88.3-143) (P = .011). An ESR > 107.5 predicted failure with a sensitivity of 51.5 and specificity of 85.2. ESR > 107.5 correlated to failure (OR 6.60, CI 2.29-19.0, P < .001). Repeat DAIRs were strongly correlated to failure (OR 5.27, CI 1.99-13.9, P < .01). CONCLUSION: DAIR failure is associated with earlier time to mortality. Repeat DAIRs, elevated ESR > 107.5, and S aureus PJI are associated with treatment failure and 2-stage revision is recommended.

Forensic Application of ForenSeqTM DNA Signature Prep Kit in Zhengjiang She Ethnic Group.

OBJECTIVES: To evaluate the ability of the ForenSeqTM DNA Signature Prep kit (ForenSeq kit) in analyzing the sequence information of STRs in Zhejiang She ethnic group and its forensic application efficacy. METHODS: A total of 50 Zhejiang She ethnic group samples were sequenced with the ForenSeq kit on the MiSeq FGx platform. The data was analyzed using ForenSeqTM universal analysis software to obtain the motif structure and flank regions of the 58 STRs, then compared with PCR-CE typing results to test the consistency. At last, the allele frequency and population genetic parameters were calculated. RESULTS: A total of 448 sequence polymorphic alleles were detected in 50 samples of Zhejiang She ethnic group. Compared with fragment length polymorphism detected by PCR-CE, 82 alleles were increased by MPS detection based on ForenSeq kit, and 7 SNPs variation were detected in the flanking regions of 6 loci. The 22 male individuals were genotyped, and total 19 haplotypes were detected in 24 Y chromosome STRs of these 22 males. The cumulative discrimination power of the 27 autosomal STRs was 1-8.87×10-30, the cumulative probability of exclusion of duo-testing was 0.999 999 962 640 657, the cumulative probability of exclusion of trios-testing was 0.999 999 999 999 633. CONCLUSIONS: Based on MPS typing technology, using the ForenSeq kit greatly improves the detection efficiency. In addition, the 58 STRs have good genetic polymorphisms in Zhejiang She ethnic group, which are suitable for individual identification and paternity identification in forensic application.

Surgical Strategies for the Treatment of Bismuth Type I and II Hilar Cholangiocarcinoma: Bile Duct Resection with or Without Hepatectomy?

BACKGROUND: The role of hepatic resection in the treatment of type I and II hilar cholangiocarcinoma (HCCA) remains controversial. In the present study, we aimed to identify whether hepatic resection was necessary for type I and II HCCA. METHODS: A total of 23 patients classified as type I and II HCCA undergoing surgical resection were included in this study. The patients were divided into two groups: bile duct resection (BDR) group (n = 15) and hepatic resection (HR) group (n = 8). Systematic review and meta-analysis were performed to compare the R0 resection and long-term survival between BDR and HR for Bismuth type I and II HCCA. A total of 7 studies with 260 cases were included in this meta-analysis. RESULTS: In our cohort, the R0 resection rate was 73.3% in BDR group and 87.5% in HR group. The HR group had a higher number of postoperative complications than the BDR group (P = 0.002). There was no difference in long-term survival (P = 0.544) and recurrence (P = 0.846) between BDR and HR in Bismuth type I and II HCCA. The meta-analysis showed that HR was associated with better R0 resection rate (RR 4.45, 95% CI 2.34-8.48) and overall survival (HR 2.15, 95% CI 1.34-3.44) compared with BDR group. There was no publication bias and undue influence of any single study. CONCLUSIONS: The meta-analysis showed that HR was associated with better R0 resection rate and overall survival compared with BDR for type I and II HCCA patients. More aggressive surgical strategies should be increasingly considered for the treatment of type I and II HCCA patients.

Sarcopenia and Short-Term Outcomes After Esophagectomy: A Meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate the value of preoperative sarcopenia in predicting complications after esophagectomy. Clinicopathologic characteristics of sarcopenia patients, which may support sarcopenia management, also were studied. METHODS: This study searched for articles describing an association between sarcopenia and short-term outcomes after esophagectomy using PubMed, EMBASE, and the Cochrane Library. Mantel-Haenszel and inverse variance models were used for the meta-analyses of end points. RESULTS: The meta-analysis included 14 studies comprising a total of 2387 patients. Sarcopenia was significantly associated with advanced age (weighted mean difference [WMD], 3.48; 95% confidence interval [CI], 2.22-4.74), lower body mass index (WMD - 2.22; 95% CI - 2.65 to - 1.79), squamous cell carcinoma (odds ratio [OR], 2.78; 95% CI 1.72-4.47), advanced clinical tumor stage (OR 1.65; 95% CI 1.28-2.15), and neoadjuvant therapy (OR 1.87; 95% CI 1.38-2.53). The sarcopenia patients showed lower preoperative albumin levels (WMD - 0.11; 95% CI - 0.19 to - 0.04) than the nonsarcopenia patients. Sarcopenia was significantly predictive of pneumonia (OR 2.58; 95% CI 1.75-3.81) and overall complications (OR 1.52; 95% CI 1.07-2.15) after esophagectomy. The sarcopenia patients also showed nonsignificant increases in the risks of anastomotic leakage (OR 1.29; 95% CI 0.99-1.67), vocal cord palsy (OR 2.03; 95% CI 0.89-4.64), and major complications (≥ Clavien-Dindo grade III; OR 1.30; 95% CI 0.95-1.79) but not increased operation time, blood loss, or mortality. CONCLUSIONS: Preoperative sarcopenia assessment showed considerable potential for predicting postoperative complications for esophageal cancer patients. To realize this potential, more effective diagnostic criteria and severity classifications for sarcopenia are warranted.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a single-Centre, open-label, randomized, controlled, clinical trial (HCHTOG1903).

BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.

Palladium-Catalyzed Direct Arylation of Alkylpyridine via Activated N-Methylpyridinium Salts.

An efficient Pd-catalyzed arylation of alkylpyridine based on the pyridinium activation strategy has been developed for synthesis of mixed aryl alkylpyridines. It was found that (1) the N-methyl group in the pyridinium salts acted as a transient activator and could be automatically departed after the reaction, (2) CuBr was an indispensable additive for achieving the C6-selective arylation, (3) the α-branched alkyl chain on the alkylpyridine greatly increased the yield of the product. Deuterium labelling experiment revealed that in the case of the α-branched alkylpyridine, the presence of CuBr completely inhibited the H/D exchange at the benzylic position and thus enabled the selective arylation at the C6 position. This protocol demonstrates a broad substrate scope, and with respect to both the aryl iodides and the α-branched alkylpyridine, the desired mixed aryl alkylpyridines were obtained in generally good to excellent yields.

Dehydrogenation of Alcohols to Carboxylic Acid Catalyzed by in Situ-Generated Facial Ruthenium-CPP Complex.

A selective catalytic system for the dehydrogenation of primary alcohols to carboxylic acids using a facial ruthenium complex generated in situ from the [Ru(COD)Cl2]n and a hybrid N-heterocyclic carbene (NHC)-phosphine-phosphine ligand (CPP) has been first reported. The facial coordination model was unveiled by NMR analysis of the reaction mixture. Such a fac-ruthenium catalyst system exhibited high catalytic activity and stability, and a high turnover number of 20 000 could be achieved with catalyst loading as low as 0.002 mol %. The exceedingly high catalyst stability was tentatively attributed to both the anchoring role of NHC and the hemi-lability of phosphines. The catalytic system also features a wide substrate scope. In particular, the facial coordination of CPP ligands was found to be beneficial for sterically hindered alcohols, and ortho-substituted benzylic alcohols and bulky adamantanyl methanol as well as cholesterol were all found to be viable dehydrogenation substrates.