Copper-catalyzed [3+2] annulation of O-acyl ketoximes with 2-aryl malonates for the synthesis of 3-aryl-4-pyrrolin-2-ones.

A copper-catalyzed [3+2] annulation of O-acyl ketoximes with 2-aryl malonates for the concise synthesis of 3-aryl-4-pyrrolin-2-ones has been developed. The advantage of this method lies in the use of O-acyl oximes as an internal oxidant to generate the nucleophilic enamines and electrophilic p-quinone methides concurrently. The subsequent nucleophilic addition undergoes selectively on the α-C of malonates.

Copper-Catalyzed Annulation of O-Acyl Oximes with Cyclic 1,3-Diones for the Synthesis of 7,8-Dihydroindolizin-5(6H)-ones and Cyclohexanone-Fused Furans.

A copper-catalyzed annulation of O-acyl oximes with cyclic 1,3-diones has been developed for the concise synthesis of 7,8-dihydroindolizin-5(6H)-ones and cyclohexanone-fused furans through the substituent-controlled selective radical coupling process. 2-Alkyl cyclic 1,3-diones undergo C-C radical coupling, while 2-unsubstituted cyclic 1,3-diones undergo C-O radical coupling.

Robotic-assisted unicompartmental knee arthroplasty: a review.

PURPOSE: Presented here is an up-to-date review concerning robotic-assisted unicompartmental knee arthroplasty (rUKA), including its rationale, operative system, pros and cons. METHODS: We did a systematic research in electronic databases, including PubMed, Cochrane Library, Web of Science, and Embase up to March 30, 2020 to retrieve literature pertaining to rUKA. The search strategies "(robotic* AND knee arthroplasty OR knee replacement)" and "(knee arthroplasty OR knee replacement NOT total)" were used. Studies describing rUKA and clinical trials, dry bone or cadaveric researches regarding technologies, positioning, alignment, function, or survivorship of implants were included in this review. All retrieved studies were first browsed for eligibility on the basis of title and abstract, and the selected studies were further evaluated by reading full text for final inclusion. RESULTS: Robotic-assisted technology has been found to increase the accuracy of bone preparation and implant placement, reduce technical variability and outliers, and enhance reproduction of limb alignment. Additionally, early clinical outcomes were excellent, but mid-term follow-up showed no superiority in component survivorship. The potential drawbacks of the robotic-assisted technology include relatively-low time- and cost-effectiveness, development of some rUKA-related complications, and lack of support by high-quality literature. CONCLUSION: This review shows that rUKA can decrease the number of outliers concerning the optimal implant positioning and limb alignment. However, due to absence of extensive studies on clinical outcomes and long-term results, it remains unclear whether the improved component positioning translates to better clinical outcomes or long-term survivorship of the implant. Nevertheless, since an accurate implant position is presumably beneficial, robotic-assisted technology is worth recommendation in UKA.

High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure.

BACKGROUND: Patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) present a complex and poor prognosis. Systemic inflammation plays an important role in its pathogenesis, and interleukin-6 (IL-6) as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration. Whether serum IL-6 influences HBV-ACLF prognosis has not been studied. AIM: To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF. METHODS: We performed a retrospective study of 412 HBV-ACLF patients. The findings were analyzed with regard to mortality and the serum IL-6 level at baseline, as well as dynamic changes of serum IL-6 within 4 wk. RESULTS: The serum IL-6 level was associated with mortality. Within 4 wk, deceased patients had significantly higher levels of IL-6 at baseline than surviving patients [17.9 (7.3-57.6) vs 10.4 (4.7-22.3), P = 0.011]. Patients with high IL-6 levels (> 11.8 pg/mL) had a higher mortality within 4 wk than those with low IL-6 levels (≤ 11.8 pg/mL) (24.2% vs 13.2%, P = 0.004). The odds ratios calculated using univariate and multivariate logistic regression were 2.10 (95% confidence interval [CI]: 1.26-3.51, P = 0.005) and 2.11 (95%CI: 1.15-3.90, P = 0.017), respectively. The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%, which was significantly higher than the 6.6% mortality rate in patients with low IL-6 levels at 4 wk (hazard ratio = 2.39, 95%CI: 1.05-5.41, P = 0.037). The mortality was 5.0% in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk, 7.5% in patients with low IL-6 levels both at baseline and at 4 wk, 11.5% in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk, and 16.7% in patients with high IL-6 levels both at baseline and at 4 wk. The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant (P for trend = 0.023). CONCLUSION: A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF. Furthermore, a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Achillon versus modified minimally invasive repair treatment in acute Achilles tendon rupture.

PURPOSE: To date, the best treatment of acute Achilles tendon rupture (AATR) is still inconclusive. Achillon seems to be a promising approach with satisfactory function and low complication rate. We hypothesize a modified minimally invasive repair (MMIR), which provides direct visualization of proximal tendon stump without specialized equipment that could provide comparable results. This trial is aimed to evaluate the functional and surgical outcomes of MMIR comparing with Achillon. METHODS: From February 2013 to February 2017, 114 patients with AATR were enrolled in this trial, underwent an alternative operation (Achillon or MMIR), and accelerated rehabilitation protocol. Forty-four patients took the Achillon and the other 70 patients took the MMIR at their subjective choice. One hundred eleven full follow-up data were obtained including Achilles tendon total rupture score (ATRS), time back to work, rerupture rate, overall complication rate, and operation time. RESULTS: There was no significant difference between groups in demographic characters. There was no statistical difference between both groups regarding to time return to work and ATRS at 3rd, 6th, 12th, and 24th month, respectively. Five reruptures and two Achilles tendons tethering to skins were found in the Achillon group, and two reruptures and one sural nerve injury in the MMIR group. No wound infection and dehiscence occurred. Overall complication rate in the Achillon group is higher (16.3% vs. 4.4%, p = 0.044). The operation time of Achillon is less than MMIR (34.84 vs. 39.71, p < 0.001). CONCLUSION: Both techniques combining with accelerated rehabilitation showed to be reliable and effective. MMIR is safer and more economical, and Achillon is faster.

MiR-96-5p promotes breast cancer migration by activating MEK/ERK signaling.

BACKGROUND: Breast cancer is the leading cause of cancer deaths in women worldwide. The purpose of the current study was to investigate the potential role of miR-96-5p in breast cancer. METHODS: Breast cancer tissues and matched para-cancerous tissues were collected. The expression of microRNA-96-5p (miR-96-5p) and arginine kinase 3 (AK3) was detected by quantitative real-time PCR (qRT-PCR). The correlation between miR-96-5p and AK3 was calculated by Pearson's Chi-square test. Moreover, mimics or inhibitors of miR-96-5p were applied to explore whether miR-96-5p influences the migration capacity in Transwell and wound healing assays. Bioinformatics analysis was performed to identify the target genes of miR-96-5p through the TargetScan, miRDB and miRanda databases. A luciferase reporter assay was performed to verify AK3 as a downstream target gene of miR-96-5p. RESULTS: The expression of miR-96-5p was significantly increased in breast cancer tissue and breast cancer cell lines compared with para-cancerous tissue and a breast cell line, respectively. The expression of miR-96-5p negatively correlated with AK3 gene expression. AK3 was demonstrated to be a direct mRNA target of miR-96-5p. AK3 was positively associated with the overall survival of breast cancer patients. Kaplan-Meier curve and log rank test analyses revealed that decreased AK3 levels were significantly associated with reduced overall survival. miR-96-5p was shown to promote the migration of breast cancer cells through the MEK/ERK signaling pathway. CONCLUSION: Our results identify a role for miR-96-5p in promoting breast cancer cell migration through activation of MEK/ERK signaling by targeting AK3.

Characterization of Nucleobases in Broadband Terahertz Spectra from 0.5 to 10 THz with the Air-Biased-Coherent-Detection Technique.

Terahertz time-domain spectroscopy (THz-TDS) is an effective coherent detection technique for deeply understanding the structures and functions of biomolecules. However, generally not full information in the whole THz range can be obtained due to the limited detection bandwidth (usually less than 5 THz) of the traditional THz-TDS systems. In this paper, effective THz absorption spectra in 0.5⁻10 THz range of five typical nucleobases of DNA/RNA are characterized with a super broadband THz detection technique, called the air-biased- coherent-detection (THz-ABCD) technique. Few unexpected characteristic absorption peaks appeared in the low-frequency region and meanwhile a series of anticipated characteristic absorption peaks are found in the high-frequency region. The fingerprint spectra of these nucleobases are helpful for further analysis on the vibration and twisting behavior of hydrogen bonds, van der Waals and electrostatic forces etc. between and within DNA/RNA biomolecules.

Association between the concurrence of pre-existing chronic liver disease and worse prognosis in patients with an herb- Polygonum multiflorum thunb. induced liver injury: a case-control study from a specialised liver disease center in China.

OBJECTIVES: The present study aimed to evaluate the association between the concurrence of pre-existing chronic liver diseases (CLD) and worse prognosis in patients with HILI. DESIGN: A case-control study. SETTING: Tertiary hospital specialising in liver diseases in China. PARTICIPANTS: 145 hospitalised HILI patients were assessed with respect to prognosis by comparing HILI with or without pre-existing CLD from February 2007 to January 2017. Twenty-five HILI cases with pre-existing alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) and 200 ALD or NAFLD controls matched 1:8 for sex, age (±4 years old), body mass index (±2 kg/m2), the type of CLD, alcohol intake (±5 g/d) and the presence or absence of cirrhosis. PRIMARY OUTCOME MEASURES: Mortality and chronicity in HILI patients with or without pre-existing CLD, and matched CLD patients. RESULTS: Of the 193 714 hospitalised patients with liver diseases, 5703 patients met the diagnostic criteria for drug-induced liver injury (DILI), which was attributed to Polygonum multiflorum Thunb. (PMT) in 145 patients. Among these HILI patients, 22.8% (33 of 145) had pre-existing CLD, including 17 (51.5%) with ALD, 8 (24.2%) with NAFLD, 5 (15.2%) with chronic viral hepatitis and 3 (9.1%) with autoimmune liver disease. Compared with HILI patients without CLD, HILI patients with pre-existing CLD showed higher mortality (0.9% vs 9.1%, p=0.037) and higher chronicity (12.5% vs 30.3%, p=0.016). Compared with matched ALD (136 patients) or NAFLD (64 patients) patients, HILI patients with pre-existing ALD showed higher chronicity (35.3% vs 11.8%, p=0.019). Multivariate logistic regression analysis found that concurrence of pre-existing CLD was an independent risk factor for both of chronicity and mortality (OR 3.966, 95% CI 1.501 to 10.477, p=0.005), especially the chronicity (OR 3.035, 95% CI 1.115 to 8.259, p=0.030). CONCLUSIONS: Concurrence of pre-existing CLD could be an independent risk factor for worse prognosis, especially chronicity, in PMT-related HILI.

[Autogenous femoral head bone grafting combined with total hip arthroplasty for the treatment of old dislocation of hip joint center in 16 cases].

OBJECTIVE: To study effects of autogenous femoral head bone grafting combined with total hip replacement for the treatment of old center dislocation of hip joint, and to evaluate the superiority of acetabular defect reconstruction with autogenous bone. METHODS: From March 2008 to December 2013, 16 patients (16 hips) with old center dislocation of hip joint were treated with autologous bone graft combined with total hip replacement. There were 11 males and 5 females, ranging in age from 41 to 72 years old, with an average of 56.3 years old. The duration of the disease ranged from 3.6 to 37.2 years. Twelve patients had injuries caused by traffic accidents and 4 patients were caused by falling down. The hip joint pain at the first month after operation, Harris score and hip joint movement of all patients were observed by using electronic case follow-up system. RESULTS: All the patients were followed up, and the duration ranged from 11 to 78 months, with an average of 27.3 months. The postoperative hip joint movement of (56.2±23.4)° VAS 86.3±7.2 and Harris score 32.6±12.6 were all better than preoperative (181.8±17.6)°, 11.1±2.6 and 86.3±7.2. The joint pain was reduced and the function limitation was improved after operation, and the prosthesis position was good. CONCLUSION: When the autologous femoral head bone grafting combined with total hip arthroplasty is used to treat old hip central dislocation, the initial and long-term stability of acetabular bone grafting is good, and the technique can avoid allogeneic bone complications, bone source rationally and reduce the economic burden of patients.

Metabolomic Profiling of Autoimmune Hepatitis: The Diagnostic Utility of Nuclear Magnetic Resonance Spectroscopy.

Autoimmune hepatitis (AIH) is often confused with other liver diseases because of their shared nonspecific symptoms and serological and histological overlap. This study compared the plasma metabolomic profiles of patients with AIH, primary biliary cirrhosis (PBC), PBC/AIH overlap syndrome (OS), and drug-induced liver injury (DILI) with those of healthy subjects to identify potential biomarkers of AIH. Metabolomic profiling and biomarker screening were performed using proton nuclear magnetic resonance spectroscopy (1H NMR) coupled with a partial least-squares discriminant analysis. Compared with the levels in healthy volunteers and other liver disease patients, AIH patients exhibited relatively high levels of plasma pyruvate, lactate, acetate, acetoacetate, and glucose. Such metabolites are typically related to energy metabolism alterations and may be a sign of metabolic conversion to the aerobic glycolysis phenotype of excessive immune activation. Increased aromatic amino acids and decreased branched-chain amino acids were found in the plasma of AIH patients. The whole NMR profiles were stepwise-reduced, and nine metabolomic biomarkers having the greatest significance in the discriminant analysis were obtained. The diagnostic utility of the selected metabolites was assessed, and these biomarkers achieved good sensitivity, specificity, and accuracy (all above 93%) in distinguishing AIH from PBC, DILI, and OS. This report is the first to present the metabolic phenotype of AIH and the potential utility of 1H NMR metabolomics in the diagnosis of AIH.