Establishment and validation of a predictive model for tracheotomy in critically ill patients and analysis of the impact of different tracheotomy timing on patient prognosis.

BACKGROUND: In critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial. METHODS: Clinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed. RESULTS: A total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876-0.919), and 0.896 (95% CI: 0.866-0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups. CONCLUSION: The prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.

Mice harboring the T316N variant in the GABAAR γ2 subunit exhibit sleep-related hypermotor epilepsy phenotypes and hypersynchronization in the thalamocortical pathway.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by seizures that predominantly occur during sleep. The pathogenesis of these seizures remains unclear. We previously detected rare variants in GABRG2, which encodes the γ2 subunit of γ-aminobutyric acid type A receptor (GABAAR), in patients with SHE and demonstrated that these variants impaired GABAAR function in vitro. However, the mechanisms by which GABRG2 variants contribute to seizure attacks during sleep remain unclear. METHODS: In this study, we designed a knock-in (KI) mouse expressing the mouse Gabrg2 T316N variant, corresponding to human GABRG2 T317N variant, using CRISPR/Cas9. Continuous video-electroencephalogram monitoring and in vivo multichannel electrophysiological recordings were performed to explore seizure susceptibility to pentylenetetrazol (PTZ), alterations in the sleep-wake cycle, spontaneous seizure patterns, and synchronized activity in the motor thalamic nuclei (MoTN) and secondary motor cortex (M2). Circadian variations in the expression of total, membrane-bound, and synaptic GABAAR subunits were also investigated. RESULTS: No obvious changes in gross morphology were detected in Gabrg2T316N/+ mice compared to their wild-type (Gabrg2+/+) littermates. Gabrg2T316N/+ mice share key phenotypes with patients, including sleep fragmentation and spontaneous seizures during sleep. Gabrg2T316N/+ mice showed increased susceptibility to PTZ-induced seizures and higher mortality after seizures. Synchronization of the local field potentials between the MoTN and M2 was abnormally enhanced in Gabrg2T316N/+ mice during light phase, when sleep dominates, accompanied by increased local activities in the MoTN and M2. Interestingly, in Gabrg2+/+ mice, GABAAR γ2 subunits showed a circadian increase on the neuronal membrane and synaptosomes in the transition from dark phase to light phase, which was absent in Gabrg2T316N/+ mice. CONCLUSION: We generated a new SHE mouse model and provided in vivo evidence that rare variants of GABRG2 contribute to seizure attacks during sleep in SHE.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

A 12 Week Fetus with Anophthalmia, Limb Anomalies and Infratemporal Teratoma.

Background: Microphthalmia is a rare autosomal recessive condition commonly known as Waardenburg anophthalmia syndrome (WAS) or oculo-acromal formation syndrome (MIM#206920). Case Description: Here, we report the case of a woman whose fetal ultrasonography at 12 weeks of pregnancy revealed multiple fetal abnormalities. These included the absence of the left upper limb, an unclear display of the right orbit, a visible maxillary space, and a round, echoless appearance measuring 4 mm in diameter in the middle of the forehead. There was also a significant echo in the sac wall. The possibility of a frontal meningocele or a proboscis-like nose was considered. The fetus was delivered with absence of the left upper limb, absence of the right eye, a cleft lip on the right side, and a milky white sac with a diameter of 5 mm on the forehead after the pregnancy was terminated at the hospital. Pathological investigation revealed a mature cystic teratoma. The conclusion was microphthalmia with limb anomalies (MLA) after missing limbs, absence of eyes, and cleft lip were input into the Online Mendelian Inheritance in Man database. The case was diagnosed with fetal microphthalmia with limb anomalies and an interfrontal teratoma. Conclusion: In this case, the entire exon analysis was not conducted, and as a result, the final diagnosis remains unclear. Based exclusively on the phenotype of the induced fetus, MLA was diagnosed. It is proposed that cases satisfying the requirements for a pathological diagnosis should undergo a pathological examination to establish a definitive diagnosis.

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice.

BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

On the genus Tegestria Roewer, 1936, new senior synonym of Gintingius Roewer, 1938 with the description of a new species (Opiliones: Epedanidae: Sarasinicinae).

Tegestria altmannae sp. nov. is described and illustrated based on male and female specimens collected in Malaysia. It is characterized by the unarmed dorsal scutum, and basal segment of chelicerae dorsally with three seta-tipped tubercles. The type species of the monotypic genus Gintingius Roewer, 1938, G. robustus Roewer, 1938, is treated as a new synonym of Tegestria coniata Roewer, 1938 and the genus Gintingius as a new synonym of Tegestria Roewer, 1936, accordingly.

Research progress of rhizosphere microorganisms in Fritillaria L. medicinal plants.

The soil's rhizosphere is a highly active place where the exchange of substances and information occurs among plants, soils, and microorganisms. The microorganisms involved are crucial to the activities of plant growth and development, metabolism, and reproduction. Fritillaria L. medicinal plants are unique Chinese medicinal ingredients, but the continuous cropping obstacles formed in the artificial planting process is severely harmful to the growth and development of these medicinal plants. In this review, we summarized the current species and distribution of Fritillaria L. in China, and analyzed the changes in microbial diversity (mainly among bacteria and fungi) in the rhizosphere of these plants under long-term continuous cropping. The fungi showed an increasing trend in the soil rhizosphere, resulting in the transition of the soil from the high-fertility "bacterial type" to the low-fertility "fungal type" as planting years increased. Furthermore, the interaction between Fritillaria L. medicinal plants and the rhizosphere microorganisms was reviewed, and promising applications for the rhizosphere microbiome in the cultivation of Fritillaria L. medicinal plants were suggested. It is expected that this review will facilitate the in-depth understanding of rhizosphere microorganisms in the growth, accumulation of active ingredients, and disease control of Fritillaria L.

Corneal histomorphology and electron microscopic observation of R124L mutated corneal dystrophy in a relapsed pedigree.

AIM: To investigate the histological characteristics and ultrastructure of recurrent Chinese R124L mutated corneal dystrophy after keratoplasty. METHODS: The subjects were enrolled from a Chinese family of corneal dystrophy with R124L heterozygous gene mutation and with a history of consanguineous marriage. Normal corneal samples were used as controls. RESULTS: In this family, 2 patients (3 eyes) underwent penetrating keratoplasty (PKP) and 2 patients (4 eyes) underwent lamellar keratoplasty (LKP). They had recurrence at 33.5±3.0 (range 30-36)mo after keratoplasty. Among them, 1 patient (1 eye) underwent PKP again and 1 patient (2 eyes) underwent LKP again. In the R124L mutated recurrent corneal dystrophy, the corneal turbidity was mainly distributed from the upper corneal cortex to the anterior stroma; the corneal epithelium surface was rougher and more uneven; and, the corneal erosions were larger. Hematoxylin-eosin staining showed that the thickness of the corneal epithelium was uneven; the arrangement of the epithelial cells was disordered; and, some corneal epithelial cells were swollen. The results of Congo red staining, Masson's trichrome staining and Periodic acid-Schiff staining were positive, while that of Alcian blue staining was negative. Under a transmission electron microscope, deposition of high electron density substances between epithelial and basal cells, and, apoptosis of basal cells were observed. Many high electron density depositions were observed in the sub-epithelial and anterior corneal matrix. CONCLUSION: In the Chinese family of recurrent corneal dystrophy with R124L gene mutation, the corneal epithelia of the recurrent cases are rougher, and the corneal depositions are extracellular amyloid fibrin.

A modified LC-MS/MS method for the detection of whole blood tacrolimus and its clinical value in Chinese kidney transplant patients.

Background: For patients who treated with tacrolimus after kidney transplant, therapeutic drug monitoring is essential to improve their prognosis. However, previous detection methods have limitations, such as the overestimation and unacceptable bias in the immunoassays. Precision medicine has been challenged. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is recognized as the gold standard due to its accuracy and specificity, but lack of throughput and complex process limits its clinical application. Therefore, an accurate, simple and high throughput method for tacrolimus monitoring is needed for clinical practice. Methods: A modified LC-MS/MS method was introduced and validated. Whole blood samples were prepared by a one-step protein precipitation method. Chromatographic separation was achieved using a Phenomenex Kinetex 2.6 µm XB-C18 2.1 × 50 mm column with a total run time of 3.5 min to avoid matrix effect. An electrospray ionization source (ESI) was used in positive ion multiple reaction monitoring (MRM) mode for mass spectrometric detection. In order to protect the mass spectrometer, only part of the sample after LC separation was allowed to enter the mass spectrum, through a two HPLC systems coupled one mass spectrometry design. In this way, the instrument throughput is also improved and realizing the detection of 2 samples within 3.5 min and carried out a shorter analyzing time for each sample of 1.75 min. Additionally, we calculated tacrolimus-intrapatient variant (Tac-IPV) based on this modified method and assessed the prognostic value of Tac-IPV in Chinese kidney transplant patients. Results: The LC-MS/MS was modified by streamlining the procedure and increasing the throughput. The method proved to be accurate and reproducible with all performance parameters suitably meeting the clinical requirements over a calibration ranged from 0.37 to 42.90 ng/mL. Parameters such as linearity, limit of quantification (LoQ) and dilution integrity were validated with a clinical reportable range from 0.37 to 343.20 ng/mL, which was particularly useful for high drug concentrations patients (rare but very serious). Both cross-contamination and matrix effects were negligible. Clinical data of 83 patients showed that Tac-IPV was associated with poor kidney transplant outcome in Chinese (Hazard Ratio (HR) = 3.96, 4.75; 95% Cl: 1.10-14.21, 1.23-18.36; P < 0.05). Conclusions: This modified LC-MS/MS method possessed high throughput and simple sample preparation, allowing it to meet daily clinical needs. At the same time, Tac-IPV based on this modified LC-MS/MS had excellent prognostic value in kidney transplantation. These advantages have great significance for the individualized treatment of Chinese kidney transplant patients and broad application of Tac-IPV.

Long Noncoding RNA RP11-732M18.3 Promotes Glioma Angiogenesis by Upregulating VEGFA.

Gliomas are the most aggressive and common type of malignant brain tumor, with limited treatment options and a dismal prognosis. Angiogenesis, a hallmarks of cancer, is one of two critical events in the progression of gliomas. Accumulating evidence has demonstrated that in glioma dysregulated molecules like long noncoding RNAs (lncRNAs), are closely linked to tumorigenesis and prognosis. However, the effects of and mechanisms of action of lncRNAs during tumor angiogenesis are poorly understood. The effect of lncRNA RP11-732M18.3 on angiogenesis was elucidated through an intracranial orthotopic glioma model, immunohistochemistry, and an in vitro angiogenesis assay. Co-culture experiments and cell migration assays were performed to investigate the function of lncRNA RP11-732M18.3 in vitro. lncRNA RP11-732M18.3 increased CD31+ microvessel density, and overexpression of lncRNA RP11-732M18.3 resulted in poor mouse survival. lncRNA RP11-732M18.3 promoted endothelial cell migration and tube formation. Nomogram and Kaplan-Meier survival analyses indicated that higher VEGFA is correlated with a poor prognosis. Mechanistically, lncRNA RP11-732M18.3 promotes angiogenesis by increasing the nuclear level of EP300 and facilitating the transcription and secretion of VEGFA. Our study contributes to the latest understanding of glioma angiogenesis and prognosis. lncRNA RP11-732M18.3 may be a potential treatment target in glioma.

A case report of otoendoscopic radiofrequency resection of squamous cell carcinoma of the external auditory canal.

Squamous cell carcinoma is the most common pathological type of external and middle ear malignancy. Squamous cell carcinoma of the external auditory canal and middle ear is closely associated with long-term chronic inflammatory irritation. The patient was admitted with a major complaint of a "stuffy feeling in the left ear for more than three months." The results of the otoendoscopic examination were as follows: The left external auditory canal was filled with a granuloma-shaped mass with an unsmooth surface that showed obvious oozing of blood. The tympanic membrane was not visible. After the completion of the relevant examinations, radiofrequency resection of the external auditory canal mass was performed under otoendoscopy and the wound healed well with postoperative dressing changes. Pathological results revealed a well-differentiated keratinizing cutaneous squamous cell carcinoma and there was no recurrence throughout the next 5 years after the operation. Proper preoperative evaluation and the correct selection of surgical approaches can be of great importance. The primary complication of ear squamous cell carcinoma was local recurrence with a low incidence of metastasis. Early and complete resection was determined to be the optimal course of treatment.

Rare variants in GABRG2 associated with sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome. The underlying pathophysiology is presumed to be closely related with disruption of GABAergic neurotransmission, which is mainly medicated by γ-aminobutyric acid type A receptor (GABAAR). Thus, it is reasonable to assume that rare GABAAR variants might contribute to the pathogenesis of SHE. To test this hypothesis, we performed next-generation sequencing in 58 SHE patients and analyzed the functional effects of the identified variants in both neuronal and non-neuronal cells using a combination of electrophysiology recordings, western blot, flow cytometry, and confocal microscopy. In our study, we detected three rare variants (NM_198904.2: c.269C > T, p.T90M; NM_198904.2: c.950C > A, p.T317N and NM_198903.2: c.649C > T, p.Q217X) in GABRG2 (MIM:137,164, encoding GABAAR γ2 subunit) in three unrelated patients. Two of the three rare variants were transmitted unaffected maternally (T90M) or unaffected paternally (Q217X), whereas the T317N variant arose de novo. The mother of proband carrying the T90M variant was unaffected and being mosaicism for this variant. Functional analysis showed that T90M and T317N variants decreased GABA-evoked current amplitudes by diverse mechanisms including impaired surface expression, endoplasmic reticulum retention, and channel gating defects. And Q217X variant reduced synaptic clustering and distribution of GABAAR. While a causal role of these variants cannot be established directly from these results, the functional assessment together with the genetic sequencing suggests that these rare GABRG2 variants may constitute genetic risk factors for SHE. Our study further expands the GABRG2 phenotypic spectrum and supports the view that GABAergic neurotransmission participates in the epileptogenesis of SHE.

Overexpression of Cpg15 Alleviates the Oxidative Stress in Neuronal Cells Via Regulating Redox Enzymes and Nrf2 Antioxidative Pathway.

Oxidative stress is becoming increasingly implicated in the development of a variety of neurological disorders. However, the underlying mechanism remains elusive. In the present study, we investigated the function and related signal pathway which Cpg15, a neuronal-specific expressed neurotrophic factor, plays in the oxidative stress of neurons using a H2O2-treated N2a cell model. The results showed that the Cpg15 expression was decreased under oxidative stress, and overexpression of Cpg15 increased the activity of antioxidative SOD enzymes and decreased the expression level of prooxidative COX2 enzyme, and the level of oxidative products malondialdehyde (MDA), indicating its function and potential mechanism in alleviating the oxidative stress of cells. The results also indicated that the Nrf2/HO-1 antioxidative pathway was involved in the Cpg15-mediated alleviation of oxidative stress. Also, overexpression of Cpg15 activated the Nrf2 antioxidative pathway in the thalamus of the REM sleep-deprived mice. In conclusion, our results implied that supplemental expression of Cpg15 may alleviate oxidative stress in neuronal cells via regulating the redox enzymes or activating the Nrf2 antioxidant pathway.

Phase I study of pegylated liposomal doxorubicin and cisplatin in patients with advanced osteosarcoma.

PURPOSE: The repeated use of doxorubicin is limited due to dose-limiting cardiac toxicity. Pegylated liposomal doxorubicin (PEG-LD, Duomeisu) has a reduced cardiac toxicity. This phase I study aimed to investigate the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the PEG-LD and cisplatin combination in patients with metastatic and recurrent osteosarcoma. METHODS: Patients were given PEG-LD at a dose of 40, 50, or 60 mg/m2 on day 1 of each 21-day cycle, according to a 3 + 3 approach for dose escalation. Cisplatin was administered as a fixed dose of 100 mg/m2 for every cycle. Toxicities and tumor response were observed. RESULTS: A total of 15 patients were enrolled in this trial, and nine of the patients had received prior doxorubicin. The MTD of PEG-LD was reached at 50 mg/m2 in this regimen, with neutropenic fever and stomatitis as DTLs. The main adverse event (AE) was myelosuppression. The most common non-hematological AEs were vomiting, hypoproteinemia, stomatitis and transient sinus arrhythmia. Grade 3-4 toxicity was neutropenia, leukopenia, thrombocytopenia, anemia and stomatitis in the whole cohort. All the AEs were relieved after symptomatic and supportive treatment. Totally, the overall response rate was 13.3% and disease control rate was 66.7%. For the six patients who have not received prior doxorubicin, one partial response and five stable diseases were observed. CONCLUSION: We provide the data showing that PEG-LD 50 mg/m2 combined with cisplatin 100 mg/m2 demonstrated an acceptable safety profile and promising clinical activity in advanced osteosarcoma, which merits further evaluation in phase II studies. TRIAL REGISTRATION: ChiCTR1900021550.

The therapeutic effects of basic fibroblast growth factor in nasal vestibulitis.

OBJECTIVE: To observe the effect of topical application of recombinant human basic fibroblast growth factor (bFGF) in patients with nasal vestibulitis. METHODS: One hundred patients with nasal vestibulitis were randomly divided into two groups. Local application of bFGF + conventional medication was administered in the treatment group, while conventional medication was conducted in the control group. The healing of the nasal vestibular mucosa was observed. RESULTS: The mucosal healing time was 18.3 ± 4.8 days in the treatment group and 36.2 ± 6.2 days in the control group. The data comparison revealed that the difference between groups was statistically significant (P < 0.01). The total effective rate was 98.0% in the treatment group and 90.0% in the control group, and the difference was not statistically significant between the two groups (P > 0.05). CONCLUSION: Topical application of bFGF in patients with nasal vestibulitis could promote the growth of nasal mucosa, shorten the healing time of mucosal erosion, enhance the clinical treatment effect, and save a lot of treatment time for patients.

Transdermal Photothermal Sterilization and Abscess Elimination Research of BSA-CuS Nanoparticles in vivo.

The treatment of subcutaneous abscess caused by drug-resistant bacteria is facing great difficulties and receiving more attention. In this work, we employed BSA-CuS nanoparticles as a photothermal reagent to apply photothermal therapy (PTT) to combat drug-resistant bacteria in vitro and subcutaneous abscess in vivo. The BSA-CuS nanoparticles were found to be stable and biocompatible without cytotoxicity toward NIH3T3 and 4T1 cells. In vitro experiments showed that three species of drug-resistant pathogens, including Escherichia coli, Staphylococcus aureus, and Candida albicans, could be effectively sterilized under co-incubation with BSA-CuS nanoparticles and then irradiation with 1064 nm NIR laser via tissue penetration. BSA-CuS nanoparticles together with 1064 nm NIR laser irradiation could also effectively diminish subcutaneous abscesses caused by drug-resistant bacteria on mice under PTT and depth PTT without causing any serious side effects and organic damage in vivo.That is OK, thank you!

Efficacy and safety of anti-PD-1 inhibitor combined with nab-paclitaxel in Chinese patients with refractory melanoma.

PURPOSE: This retrospective study aimed to evaluate the combined effect of anti-PD-1 inhibitor and nanoparticle albumin-bound (nab)-paclitaxel for refractory melanoma among Chinese patients. METHODS: Data from January 2018 to March 2021 were retrospectively collected and analyzed. Sixty-four patients were eligible for analysis from a single Chinese cancer center. RESULTS: The median follow-up was 16.0 months at data cutoff. The objective response rate (ORR) was 29.7%, and the disease control rate (DCR) was 67.2% in all patients. Treatment-naïve patients had significantly higher ORR than pretreated patients (42.9% vs 13.8%, p = 0.011). Cutaneous melanoma patients with NRAS gene mutation benefited more than non-mutated patients (DCR of 100% vs. 54.5%) (p = 0.030). The median progression-free survival (mPFS) of all patients was 5.2 months and the duration of response was 10.8 months. Median duration of disease control was 7.7 months. Prior treatment-naïve patients had significantly longer PFS than those who accepted prior treatments (7.2 vs. 5.1 months, p = 0.024). Patients with abnormally high LDH level had shorter mPFS (3.6 months vs. 6.6 months, p = 0.020). Median overall survival was not reached in this study. Most patients experienced adverse events (AEs), but only 17.2% of patients experienced grade 3 severe AEs. The most common AEs were alopecia (89.1%), neutropenia (18.8%), pruritus (15.6%), and arthralgia (14.1%). Some patients had immune related AEs (irAEs). No grade 4 or 5 AEs were observed. Patients with ≥ 3 AEs or with irAEs had longer mPFS (p < 0.05). CONCLUSION: Nab-paclitaxel combined with PD-1 antibody is a well-tolerated and effective regimen for Chinese patients with refractory melanoma.

Long non­coding RNA AL355711 promotes smooth muscle cell migration through the ABCG1/MMP3 pathway.

Atherosclerosis and related cardiovascular diseases pose severe threats to human health worldwide. There is evidence to suggest that at least 50% of foam cells in atheromas are derived from vascular smooth muscle cells (VSMCs); the first step in this process involves migration to human atherosclerotic lesions. Long non­coding RNAs (lncRNAs) have been found to play significant roles in diverse biological processes. The present study aimed to investigate the role of lncRNAs in VSMCs. The expression of lncRNAs or mRNAs was detected using reverse transcription­quantitative polymerase chain reaction. The Gene Expression Omnibus datasets in the NCBI portal were searched using the key words 'Atherosclerosis AND tissue AND Homo sapiens' and the GSE12288 dataset. Gene expression in circulating leukocytes was measured to identify patients with coronary artery disease (CAD) or controls, and used to analyze the correlation coefficient and expression profiles. The protein level of ATP­binding cassette sub­family G member 1 (ABCG1) and matrix metalloproteinase (MMP)3 was determined using immunohistochemistry and western blot analysis. The analysis of mouse aortic roots was performed using Masson's and Oil Red O staining. The expression of lncRNA AL355711, ABCG1 and MMP3 was found to be higher in human atherosclerotic plaques or in patients with atherosclerotic CAD. The correlation analysis revealed that ABCG1 may be involved in the regulation between lncRNA AL355711 and MMP3 in atherosclerotic CAD. The knockdown of lncRNA AL355711 inhibited ABCG1 transcription and smooth muscle cell migration. In addition, lncRNA AL355711 was found to regulate MMP3 expression through the ABCG1 pathway. The expression of ABCG1 and MMP3 was found to be high in an animal model of atherosclerosis. The results indicated that lncRNA AL355711 promoted VSMC migration and atherosclerosis partly via the ABCG1/MMP3 pathway. On the whole, the present study demonstrates that the inhibition of lncRNA AL355711 may serve as a novel therapeutic target for atherosclerosis. lncRNA AL355711 in circulating leukocytes may be a novel biomarker for atherosclerotic CAD.