Azvudine versus paxlovid for oral treatment of COVID-19 in Chinese patients.

PURPOSE: To explore the effect of azvudine as compared to paxlovid for oral treatment of hospitalized patients with SARS-CoV-2 infection. METHODS: We analyzed data from a cohort of patients with SARS-CoV-2 infection in Shandong provincial hospital between February 15 and March 15, 2023. The primary outcome was time to sustained clinical recovery through Day 28 and secondary outcomes included the percentage of participants who died from any cause by Day 28, the average hospitilization time and expenses, the changes in liver and kidney function and adverse events. The Kaplan-Meier method and Cox regression model was used for statistical analysis. RESULTS: There was no significant difference between azvudine and paxlovid in terms of time to sustained clinical recovery (p = 0.429) and death rates (p = 0.687). As for hospitalization time and fee, no significant differences were observed between azvudine group and paxlovid group (Hospitalization time: p = 0.633; Hospitalization fee: p = 0.820). In addition, there were no significant differences in the effects of the two drugs on liver and kidney function (p > 0.05). CONCLUSION: Among adults who were hospitalised with SARS-CoV-2 infection, azvudine was noninferior to paxlovid in terms of time to sustained clinical recovery, death rates, hospitalization time and cost, with few safety concerns. TRIAL REGISTRATION: ChiCTR2300071309; Registered 11 May 2023. LEVEL OF EVIDENCE: Level III; Retrospective cohort study.

Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion.

The diagnostic value of the 9P21 gene determined using fluorescence in situ hybridization (FISH) combined with BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) expression detection by immunohistochemistry, was investigated in serous effusion samples of malignant mesothelioma. A total of 70 serous disease samples with serous effusion were collected from June 2017 to June 2020. Following biopsy specimen pathological diagnosis, samples were divided into malignant mesothelioma and benign mesothelioma. Differential expression of BAP1 and MTAP genes were identified in mesothelioma and mesenchymal hyperplasia. The 9P21 gene fragment was lost in mesothelioma. The positive rates of FISH, BAP1 and MTAP in biopsy specimens were 98.00, 94.00 and 90.00%. The specificity of the three were 96.00, 85.71 and 77.27%, the sensitivity were 90.00, 95.92 and 93.75%, and the positive rate of the combined detection of the three was 93.33%. The positive rate of serous fluid samples detected by the three methods (9P21 FISH probe combined with BAP1 and MTAP expression detected immunohistochemically) was 96.00, 92.00 and 88.00%, the specificity were 90.00, 77.27 and 71.43%, the sensitivity was 96.00, 93.75 and 89.80%, and the positive rate of the three combined detections was 91.33%. It was demonstrated that there was a high consistency between serous fluid samples and biopsy samples. According to clinicopathological analysis, sex, age, lesion site, Ki67 had little association with the occurrence and development of malignant mesothelioma, while asbestos exposure history was closely associated to the occurrence of mesothelioma. A high level of BAP1 gene was positively associated with the prognosis of mesothelioma, while a high level of MTAP gene was negatively associated with the prognosis of mesothelioma (P<0.05). Therefore, 9P21 FISH probe combined with BAP1 and MTAP can be used as a new method for the detection of malignant mesothelioma, and provide an important basis for the early diagnosis of mesothelioma.

Mid-infrared hyperchaos of interband cascade lasers.

Chaos in nonlinear dynamical systems is featured with irregular appearance and with high sensitivity to initial conditions. Near-infrared light chaos based on semiconductor lasers has been extensively studied and has enabled various applications. Here, we report a fully-developed hyperchaos in the mid-infrared regime, which is produced from interband cascade lasers subject to the external optical feedback. Lyapunov spectrum analysis demonstrates that the chaos exhibits three positive Lyapunov exponents. Particularly, the chaotic signal covers a broad frequency range up to the GHz level, which is two to three orders of magnitude broader than existed mid-infrared chaos solutions. The interband cascade lasers produce either periodic oscillations or low-frequency fluctuations before bifurcating to hyperchaos. This hyperchaos source is valuable for developing long-reach secure optical communication links and remote chaotic Lidar systems, taking advantage of the high-transmission windows of the atmosphere in the mid-infrared regime.

Frequency noise reduction of delay-coupled quantum cascade lasers.

This work theoretically investigates the frequency noise and spectral linewidth characteristics of mutually delay-coupled quantum cascade lasers, which are operated in the stable locking regime. We demonstrate that the mutual injection significantly reduces the frequency noise at proper coupling phases. However, the relative intensity noise is insensitive to the mutual injection. Influences of the pump current, the linewidth broadening factor, the coupling phase, and the delay time on the frequency noise are discussed as well. In addition, it is found that the appearance of multiple compound laser modes can deteriorate the frequency noise performance of the lasers.

Relative intensity noise of a mid-infrared quantum cascade laser: insensitivity to optical feedback.

This article experimentally demonstrates that the relative intensity noise (RIN) of a mid-infrared quantum cascade laser is insensitive to the optical feedback for feedback ratios up to 31% (-5.1 dB). The RIN of the free-running laser is in the range of -150 dB/Hz to -160 dB/Hz, while the optical feedback induced RIN variation is less than ± 2.0 dB. In addition, the feedback-induced lasing frequency variation is less than 2.0 GHz. Rate equation analyses of the laser are in good agreement with the experimental observations.

Frequency noise suppression of optical injection-locked quantum cascade lasers.

This work theoretically investigates the frequency noise (FN) characteristics of quantum cascade lasers subject to the optical injection through a set of coupled rate equations with Langevin noise sources. It is shown that the low-frequency FN is completely suppressed by the optical injection, and the suppression bandwidth increases with the increasing injection ratio. The optimal FN peak suppression ratio at an injection ratio of 10 dB reaches 2.9 dB. In addition, it is found that the optical injection at positive frequency detunings close to the locking boundary invokes an additional peak in the FN spectrum, which can be higher than the carrier noise-induced one of free-running lasers. This peak amplitude strongly depends on the value of the linewidth broadening factor. Unlike injection-locked interband lasers, the FN peak does not necessarily exhibit a resonance.

TASK-1 induces gefitinib resistance by promoting cancer initiating cell formation and epithelial-mesenchymal transition in lung cancer.

Cancer initiating cell (CIC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in lung cancer cell invasion and metastasis. They have been shown to occur in gefitinib resistance. Studying the molecular mechanisms of CICs, EMT and acquired gefitinib resistance will enhance the understanding of the pathogenesis and progression of the disease and offer novel targets for effective therapies. TWIK-related acid-sensitive K(+) (TASK-1) is expressed in a subset of non-small-cell lung cancer (NSCLC) cell lines, where it promotes cell proliferation while inhibiting apoptosis. In the present study, TASK-1 was demonstrated to induce gefitinib resistance in the A549 NSCLC cell line. Overexpression of TASK-1 promoted the acquisition of CIC-like traits by A549 cells. CD133, octamer-binding transcription factor 4 (OCT-4) and Nanog have been suggested to be markers of CICs in lung cancer. It was demonstrated that overexpression of TASK-1 promoted CD133, OCT-4 and Nanog protein expression in A549 cells. Increased formation of stem cell-like populations results in EMT of cancer cells. The present study found that overexpression of TASK-1 promoted EMT of A549 cells. Thus, downregulation of TASK-1 may represent a novel strategy for EMT reversal, decreasing CIC-like traits and increasing gefitinib sensitivity of NSCLCs.

Rate equation modeling of the frequency noise and the intrinsic spectral linewidth in quantum cascade lasers.

This work theoretically investigates the frequency noise (FN) characteristics of quantum cascade lasers (QCLs) through a three-level rate equation model, which takes into account both the carrier noise and the spontaneous emission noise through the Langevin approach. It is found that the power spectral density of the FN exhibits a broad peak due to the carrier noise induced carrier variation in the upper laser level, which is enhanced by the stimulated emission process. The peak amplitude is strongly dependent on the gain stage number and the linewidth broadening factor. In addition, an analytical formula of the intrinsic spectral linewidth of QCLs is derived based on the FN analysis. It is demonstrated that the laser linewidth can be narrowed by reducing the gain coefficient and/or accelerating the carrier scattering rates of the upper and the lower laser levels.

Early enteral and parenteral nutritional support after hepatectomy in patients with hepatic carcinoma: a systematic review and meta-analysis.

BACKGROUND: This study sought to conduct a systematic review providing a comparative analysis of enteral nutrition (EN) and parenteral nutrition (PN) after hepatectomy. METHODS: PubMed, Embase, and the China National Knowledge Infrastructure databases were searched for publications describing randomized controlled trials that compared early EN and PN after hepatectomy. The time period for this search was from January 1990 to December 2013. In accordance with the inclusion criteria of this study, two researchers independently screened the retrieved literature, extracted data, and assessed methodological quality. A meta-analysis of the included publications was then performed using RevMan 5.2 software. RESULTS: The meta-analysis results indicated statistically significant differences between the group that received EN and the group that received PN during the early stages after hepatectomy with respect to average total bilirubin and alanine aminotransferase levels after nutrition, pre-albumin levels, incidence of diarrhea and abdominal bloating, time to flatus, and average cost of nutrition. To varying degrees, better results were observed in the EN group than in the PN group for these metrics. CONCLUSION: During the early stages after hepatectomy, EN has obvious advantages relative to PN; thus, EN merits more widespread promotion and application in this clinical context.

[Effects of trichostatin A and paclitaxel on apoptosis and mitochondrial membrane potential of human endometrial carcinoma Ark2 cells].

BACKGROUND & OBJECTIVE: Patients suffered from advanced endometrial cancer have poor prognosis. The five-year survival is only 25%. Histone deacetylase inhibitors have shown promise in the treatment for a variety of malignancies. In combination with traditional cytotoxic chemotherapy, histone deacetylase inhibitors can enhance the survival rate of cancer patients. This study was to investigate the effect and mechanism of trichostatin A (TSA), a histone deacetylase inhibitor, combined with paclitaxel (PTX) on the apoptosis of human endometrial carcinoma cell line Ark2. METHODS: Ark2 cells were cultured in RPMI-1640 and treated with PTX alone, TSA alone or the two drugs in combination. Cell apoptosis was detected using Annexin V and Hoechst staining; perturbation of mitochondrial membrane potential was detected using MitoTracker red Poly (ADP-ribose) polymerase; caspase-9 degradation products and tubulin acetylation were detected by Western blot. RESULTS: Results of Annexin V showed that PTX (1.5 nmol/L) plus TSA (25 nmol/L) induced a significantly higher apoptotic rate (45.2%) than PTX alone (14.1%) or TSA alone (11.2%) did in Ark2 cells after drug treatment for three days. The results of Hoechst staining and Annexin V were consistent. A loss of mitochondrial membrane potential could activate the apoptotic cascade. Cleavages of PARP and caspase-9 were significantly apparent in PTX plus TSA group than in PTX group or TSA group (P<0.05). PTX and TSA could induce tubulin acetylation. PTX in combination with TSA increased acetylated tublins and microtubule stability compared with either drug alone. The loss of mitochondrial membrane potential was more dramatic in the drug combination group than the single drug group. The effects of TSA and PTX were synergistic (q=2.54). CONCLUSION: TSA and PTX could induce apoptosis of Ark2 cells, which may be through the loss of mitochondrial membrane potential and acetylation of non-histone proteins induced by histone deacetylase inhibitors.