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Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.
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Corticosteroides , Quimioterapia Combinada , Inibidores de Checkpoint Imunológico , Síndrome de Stevens-Johnson , Inibidores do Fator de Necrose Tumoral , Humanos , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/mortalidade , Síndrome de Stevens-Johnson/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Idoso , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Resultado do Tratamento , Infliximab/uso terapêutico , Infliximab/efeitos adversosRESUMO
With the rapid development of high and new technology, rubidium and its compounds show broad application prospect and market demand with their unique characteristics. At present, the production of rubidium metal is mainly prepared by calcium thermal reduction of rubidium chloride. Rubidium metal obtained by reduction requires multi-step vacuum distillation to obtain high-purity rubidium metal. The purity of rubidium metal depends on the purity of the raw material rubidium chloride. Rubidium metal is relatively active and is easy to oxidize and explode in air. Therefore, a method combining vacuum decomposition and vacuum distillation to reduce impurity elements in rubidium chloride from raw materials is proposed in this paper. The experimental results show that under the conditions of pressure of 5-10 Pa, distillation temperature of 823 K and vacuum distillation time of 60 min, the contents of Si and Zn impurities are reduced from 1206 mg/kg and 310 mg/kg to less than 0.1 mg/kg, and the removal rates are 99.99% and 99.97%, respectively. Rubidium chloride has almost no loss, and through one-step vacuum distillation, the impurity elements silicon and zinc can be deeply removed, reducing the flammability and explosiveness, high cost, long process and other problems caused by the subsequent preparation of high-purity rubidium metal.
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BACKGROUND: The present study aimed to compare the clinical and radiologic outcomes of oblique lumbar interbody fusion (OLIF) combined with lateral screw fixation and minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) for the treatment of single-level degenerative lumbar spondylolisthesis (DLS). METHODS: Data regarding clinical and radiologic outcomes for single-level DLS treated using OLIF combined with lateral screw fixation or Mis-TLIF between November 2017 and June 2020 were retrospectively analyzed. RESULTS: Seventy-five patients with single-level DLS (≥2 years' follow-up) were included and divided into two groups according to the surgical method used: OLIF (n = 33) and Mis-TLIF (n = 42). Operative time, intraoperative blood loss, and length of hospital stay were significantly lower in the OLIF group than that in the Mis-TLIF group. There were no significant differences in preoperative low back pain (LBP), leg pain (LP), visual analog scale (VAS) scores, and Oswestry Disability Index (ODI) between the two groups, although the OLIF group had significantly lower LBP VAS scores at 1, 3, and 6 months postoperatively. Additionally, the LP VAS score was significantly lower in the Mis-TLIF group than that in the OLIF group at 1 month postoperatively, and the ODI of the OLIF group at 3 months postoperatively was significantly lower than that of the Mis-TLIF group. There was no significant difference in the preoperative and postoperative lumbar lordosis angles between the two groups, whereas the postoperative surgical segmental lordosis angle and disk height (at 1, 6, 12, and 24 months) in the OLIF group were significantly higher than those in the Mis-TLIF group. Additionally, there was no significant difference in complication rates between the two groups (18.2% in the OLIF group vs. 11.9% in the Mis-TLIF group; p = 0.520). CONCLUSION: OLIF combined with lateral screw fixation yielded better clinical and radiologic outcomes than Mis-TLIF in patients with single-level DLS.
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Graphene/silicon heterojunction photodetectors suffer from a high dark current due to the high surface states and low barrier height at the interface, which limits their application. In this study, we introduce an HfOx interfacial layer via magnetron sputtering to address this issue. With this new structure, the dark current is reduced by six times under a bias voltage of -2 V. Under 460 nm illumination, the responsivity is 0.228A/W, the detectivity is 1.15 × 1011 cmHz1/2W-1, and the noise equivalent power is 8.75 × 10-5 pW/Hz1/2, demonstrating an excellent weak light detection capability. Additionally, the oxygen vacancies in the HfOx interfacial layer provide a conductive channel for charge carriers, resulting in a 2.03-fold increase in photocurrent and an external quantum efficiency of 76.5%. The photodetector maintains good photoresponse ability at a low bias voltage. This work showcases the outstanding performance of HfOx films as interfacial layer materials and provides a new solution for high-performance photodetectors, as well as a new path to improve the photovoltaic conversion efficiency of solar cells.
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Elefantíase , Linfedema , Humanos , Elefantíase/diagnóstico , Elefantíase/etiologia , Extremidade InferiorRESUMO
With the extensive use of lithium-ion batteries (LIBs), neglecting to recycle graphite anodes from LIBs leads to environmental pollution and the waste of graphite resources. Thus, developing an efficient and environment-protecting approach to reusing spent graphite anodes is necessary. Here, high value-added graphene sheets (GS), carbon nanohorns (CNHs), fluorine-doped CNHs (F-CNHs), and amorphous carbon nanoballs (ACNs) were prepared from spent graphite anodes of LIBs via DC arc plasma. In order to control the conversion of spent graphite anodes into various carbon nanomaterials, the growth mechanism of carbon nanomaterials is investigated by quenching rate. Benefiting from the extremely high quenching rates (>1.8 × 106 K/s) produced by DC arc plasma, the particle size of the prepared ACNs and CNHs is small and evenly distributed. The CNHs show a "dahlia-like" structure, and the number of graphene layers is only 3-8. Furthermore, the structural transformation mechanism of carbon nanomaterials is researched by deposition temperature. The ACNs, few-layer GS, and CNHs produced by the high quenching rates are unstable and prone to structural transformation. When these carbon nanomaterials are deposited on the cathode surface and cathode holder, the ACNs, "dahlia-like" CNHs, and GS undergo processes of fusing and overlaying at high temperatures, respectively, resulting in the agglomeration and increased particle size of ACNs and "seed-like" CNHs. Meanwhile, the GS is bent and converted into carbon nanocages (CBCs). Overall, the carbon nanomaterials prepared using spent anodes from LIBs by arc plasma are a facile, environment-friendly, and economical strategy to achieve high value-added utilization of the graphite.
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Grafite , Nanoestruturas , Grafite/química , Carbono/química , Lítio/química , Íons , Nanoestruturas/química , EletrodosRESUMO
Background/purpose: At present, there are no recognized guidelines or consensus for the treatment strategy of the asymptomatic tooth with external root resorption caused by an embedded tooth (et-ERR). Most clinicians would like prophylactic or concomitant root canal therapy (RCT) along with the extraction of the embedded tooth. The purpose of this study was to report the prognosis of external root resorption (ERR) and investigate the possibility to preserve the vital pulp of ERR tooth. Materials and methods: The patients who had asymptomatic et-ERR teeth were included. After extraction of the embedded tooth, the clinical process, prognosis, and adverse events were observed, including symptoms, clinical, and radiographic examination throughout the follow-up period. Results: A total of four cases with special features were reported. Over a follow-up period of up to 12 months, on clinical examination, 3 ERR teeth preserved pulp vitality without additional intervention except for tooth extraction and have kept normal function free from any symptoms. Radiographic examination showed bone regeneration and recovery of periodontal tissue. While one case failed to keep the vital pulp and ended in intentional replantation. Conclusion: As to et-ERR, if the embedded tooth can be promptly extracted with a minimally invasive technique and effective infection control, the pulp vitality of the et-ERR tooth is likely to be preserved. In this situation, the preferred management of asymptomatic et-ERR tooth is just followed up without prophylactic RCT.
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BACKGROUND: Nail apparatus melanoma is a malignant tumor with a high incidence in Chinese melanoma patients. Slow Mohs micrographic surgery is an emerging technique for treating nail apparatus melanoma in situ (NAMIS). OBJECTIVE: This study evaluated the efficacy and safety of slow Mohs micrographic surgery for treating NAMIS. METHODS: Patients were enrolled in this retrospective study and treated in a single center from October 1, 2016, to June 30, 2022. Each patient underwent standard slow Mohs micrographic surgery, and follow-up was regularly conducted at clinics. RESULTS: Ten patients were enrolled in the study. Two patients underwent one Mohs stage, seven underwent two Mohs stages, and one underwent seven Mohs stages. The resection margin ranged from 5 to 25 mm. No severe complications were reported in the treatment, and recurrence of NAMIS was not observed during the follow-up period. CONCLUSION: Slow Mohs micrographic surgery is a valuable surgical method to treat NAMIS that preserves digit function and can be well tolerated by patients.
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Melanoma , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Cirurgia de Mohs/efeitos adversos , Melanoma/cirurgia , Melanoma/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Melanoma Maligno CutâneoRESUMO
Objective: To investigate the short-term effectiveness of transverse antecubital incision in the treatment of failed closed reduction of Gartland type â ¢ supracondylar humeral fractures (SHFs) in children. Methods: Between July 2020 and April 2022, 20 children with Gartland type â ¢ SHFs who failed in closed reduction were treated with internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision. There were 9 boys and 11 girls with an average age of 3.1 years (range, 1.1-6.0 years). The causes of injuries were fall in 12 cases and fall from height in 8 cases. The time from admission to operation ranged from 7 to 18 hours, with an average of 12.4 hours. The healing of the incision and the occurrence of complications such as nerve injury and cubitus varus were observed after operation; the elbow flexion and extension range of motion after removing the gypsum, after removing the Kirschner wire, and at last follow-up were recorded and compared, as well as the elbow flexion and extension and forearm rotation range of motion at last follow-up between healthy and affected sides; the Baumann angle was measured on the X-ray film, and the fracture healing was observed. At last follow-up, the effectiveness was evaluated according to the Flynn elbow function evaluation criteria. Results: All incisions healed by first intention, and there was no skin necrosis, scar contracture, ulnar nerve injury, and cubitus varus. Postoperative pain occurred in the radial-dorsal thumb in 2 cases. The gypsum was removed and elbow flexion and extension exercises were started at 2-4 weeks (mean, 2.7 weeks) after operation, and the Kirschner wire was removed at 4-5 weeks (mean, 4.3 weeks). All the 20 patients were followed up 6-16 months, with an average of 12.4 months. The fracture healing time was 4-5 weeks, with an average of 4.5 weeks, and there was no complication such as delayed healing and myositis ossificans. The flexion and extension range of motion of the elbow joint gradually improved after operation, and there were significant differences between the time after removing the gypsum, after removing the Kirschner wire, and at last follow-up ( P<0.017). There was no significant difference in the flexion and extension of the elbow joint and the forearm rotation range of motion between the healthy and affected sides at last follow-up ( P>0.05). There was no significant difference in Baumann angle between the time of immediate after operation, after removing the Kirschner wire, and at last follow-up ( P>0.05). According to Flynn elbow function evaluation standard, 16 cases were excellent and 4 cases were good, the excellent and good rate was 100%. Conclusion: The treatment of Gartland type â ¢ SHFs in children with failed closed reduction by internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision has the advantages of complete soft tissue hinge behind the fracture for easy reduction and wire fixation, small incision, less complications, fast fracture healing, early functional recovery, reliable reduction and fixation, and can obtain satisfactory results.
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Fraturas do Úmero , Procedimentos de Cirurgia Plástica , Masculino , Feminino , Humanos , Criança , Pré-Escolar , Sulfato de Cálcio , Úmero , Fraturas do Úmero/cirurgia , Fixação Interna de Fraturas/métodos , Fios Ortopédicos , Consolidação da Fratura , Resultado do Tratamento , Amplitude de Movimento ArticularRESUMO
BACKGROUND: There are limited reports on nanoparticle albumin bound-paclitaxel (nab-paclitaxel) regimens as second- or third-line treatments for advanced esophageal squamous cell carcinoma (ESCC). Additionally, its safety and efficacy in ESCC patients after failure of first-line programmed cell death protein-1 (PD-1) blockade plus chemotherapy have not been reported. In this study, we aimed to assess the efficacy and tolerability of nab-paclitaxel regimens as second- or later-line treatment in advanced ESCC. METHODS: We retrospectively reviewed clinical data of advanced ESCC patients who participated in a randomized phase III clinical study and received serplulimab or placebo plus chemotherapy at our institution, and consecutive patients who received subsequent nab-paclitaxel-based regimens as second- or later-line treatment were included for data collection and analysis. RESULTS: A total of 39 patients were included, 25 (64.1%) received serplulimab plus chemotherapy and 14 (35.9%) received chemotherapy alone as first-line treatment. Treatment strategies included nab-paclitaxel monotherapy (7/39, 17.9%), or in combination with other chemotherapy (19/39, 48.7%), with anti-PD-1 antibodies (12/39, 30.8%) or with nimotuzumab (1/39, 2.6%). Overall, the objective response rate (ORR) and disease control rate (DCR) were 33.3% (13/39) and 61.5% (24/39), respectively. With a median follow-up of 9.7 months, the median progression-free survival and median overall survival were 5.0 and 7.9 months, respectively. The most common adverse events were neuropathy peripheral (30.8%), anemia (30.8%), neutrophil count decreased (23.1%), and nausea (20.5%). CONCLUSIONS: Nab-paclitaxel-based regimen could be a safe and effective option as second- or later-line treatment in patients with advanced ESCC, regardless of their previous exposure to PD-1 inhibitors.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Pulmonares , Nanopartículas , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/etiologia , Estudos Retrospectivos , Paclitaxel , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Background/purpose: Analysis of endoplasmic reticulum stress (ERS)-related long noncoding RNAs (LncRNAs) may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to comprehensively analyze the ERS-related LncRNAs signature and its effects on the prognosis, tumorigenesis, and tumor immune microenvironment in HNSCC. Materials and methods: The transcriptome data of HNSCC were obtained from TCGA. Least absolute shrinkage selection operator algorithm, and multivariate Cox regression were used to screen LncRNAs for the signature construction. Somatic mutation, gene enrichment, and immune infiltration analyses were further performed. Results: 458 ERS-related LncRNAs were identified and 55 of which were correlated with HNSCC prognosis. Ten ERS-related LncRNAs were selected to establish a risk prediction signature. When dividing patients into high-risk and low-risk groups by signature score, high-risk group correlated with worse survival rates (hazard ratio = 1.211; 95% confidence interval 1.123-1.306, P < 0.001). The area under the curve was 0.751 and 0.716 in the training and validation cohorts at 3-year. Moreover, high-risk group have increased somatic mutation rates and reduced infiltration abundancy of B cells and CD8+ T cells. Conclusion: The prognostic signature based on ERS-related LncRNAs may serve as a predictor of altered oncogene mutations and immune microenvironment, which provided an insight into the relationship between ERS, LncRNAs, and tumor progression.
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The Dzyaloshinskii-Moriya interaction (DMI) is an antisymmetric exchange interaction that stabilizes spin chirality. One scientific and technological challenge is understanding and controlling the interaction between spin chirality and electric field. In this study, we investigate an unconventional electric field effect on interfacial DMI, skyrmion helicity, and skyrmion dynamics in a system with broken inversion symmetry. We design heterostructures with a 3d-5d atomic orbital interface to demonstrate the gate bias control of the DMI energy and thus transform the DMI between opposite chiralities. Furthermore, we use this voltage-controlled DMI (VCDMI) to manipulate the skyrmion spin texture. As a result, a type of intermediate skyrmion with a unique helicity is created, and its motion can be controlled and made to go straight. Our work shows the effective control of spin chirality, skyrmion helicity, and skyrmion dynamics by VCDMI. It promotes the emerging field of voltage-controlled chiral interactions and voltage-controlled skyrmionics.
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Premature ovarian failure (POF) is a prevalent gynecological disease. In traditional Chinese medicine, it is believed that POF is directly related to abnormal function of the liver and kidneys. As such, regulation of the liver metabolism through the use of medicinal and edible substances is important for the treatment of POF. Pine pollen, a traditional Chinese medicinal and edible pollen variety, contains various active substances, such as sex hormones and phytohormones, which have been used to inhibit inflammation, regulate the immune system, and protect reproductive tissues. Using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS), this study examined the influence of pine pollen on the liver metabolome of cyclophosphamide-induced POF model Sprague Dawley (SD) rats. The variations in the metabolites present in the liver tissue of control SD rats, model SD rats, and SD rats treated with various doses of pine pollen or estrogen were analyzed using principal component analysis (PCA) in combination with orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical methods to reveal the mechanism of pine pollen intervention in the livers of POF SD rats. An animal model experiment was conducted using six groups of ten-week-old rats. Cyclophosphamide was administered intraperitoneally to the model group and four intervention groups at a dosage of 60 mg/kg for 1 d followed by a dosage of 10 mg/kg for 14 d. Within the following four weeks, each of the four intervention groups received the intragastric administration of 0.1, 0.5, or 1.5 g/kg bodyweight (BW) of pine pollen, or 0.075 g/kg BW of conjugated estrogens (positive control). Equal quantities of normal saline were administered to the control and cyclophosphamide-treated model groups. Subsequently, the rat livers were subject to pseudotargeted metabolomics, and a total of 687 liver metabolites were discovered using both positive and negative ions. The metabolites differing in content were screened using the t-test (p<0.05) and the fold change (FC>2 or <0.5) in univariate analysis, and the variable importance in projection (VIP>1) in multivariate analysis. It was found that in comparison with the control group, the contents of 32 metabolites significantly increased, while those of 28 metabolites significantly decreased in the model group. The majority of these metabolites were involved α-linolenic acid metabolism, vitamin B6 metabolism, and purine metabolism, along with the lysine degradation and glycolysis/gluconeogenesis metabolic pathways. Compared with the cyclophosphamide-induced model group, the estrogen group exhibited increased levels of 47 metabolites and decreased levels of 29 metabolites, wherein 34 metabolites were restored to the levels found in the control group. These metabolites mainly involved the vitamin B6, lysine, glycolysis/gluconeogenesis, arginine and proline, and cysteine and methionine metabolic pathways. In the low/medium/high-dose pine pollen groups, the contents of 34/32/34 metabolites increased, the contents of 30/37/24 metabolites decreased, and the contents of 47/38/34 metabolites were restored to the levels found in the control group, respectively. These metabolites were mainly involved in vitamin B6 metabolism, purine metabolism, and the glycolysis/gluconeogenesis metabolic pathway. These results therefore indicate that the restoring effect of pine pollen is equivalent or superior to that of conjugated estrogen. Additionally, based on the known metabolic pathways, it appears that when estrogen interferes with the liver metabolism, the key metabolic pathways that become affected are the arginine and proline metabolism and cysteine and methionine metabolism pathways. In contrast, pine pollen intervention affected existing metabolic pathways that were known to be disordered by cyclophosphamide. The use of pine pollen may therefore restore the levels of many metabolites. It should be noted that 23 overlaps exist between the estrogen-restored metabolites and the pine pollen-restored metabolites, including a variety of acylcarnitines, such as ACar 10â¶0. As a result, pine pollen extract may be able to normalize the liver metabolic abnormalities induced by POF. This study therefore establishes a theoretical reference for the development of functional applications for pine pollen and for the treatment of POF.
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Medicamentos de Ervas Chinesas , Insuficiência Ovariana Primária , Humanos , Feminino , Ratos , Animais , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Insuficiência Ovariana Primária/tratamento farmacológico , Cisteína , Lisina , Medicamentos de Ervas Chinesas/química , Metabolômica , Cromatografia Líquida de Alta Pressão , Fígado/metabolismo , Estrogênios , Ciclofosfamida , Purinas , Biomarcadores/urinaRESUMO
PURPOSE: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells. METHODS: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis. RESULTS: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3. CONCLUSION: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.
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Neoplasias do Colo do Útero , Feminino , Humanos , Apoptose/fisiologia , Proteína X Associada a bcl-2/metabolismo , Proteínas de Transporte , Caspase 3/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Células HeLa , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Processamento de RNA/genética , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: This study was designed to investigate the clinical application, efficacy, and safety of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer in the real world. METHODS: A retrospective, observational analysis was conducted on patients treated with ICIs in four tertiary hospitals in the region from January 2015 to March 2021, to evaluate the clinical efficacy of ICIs single-agent or combined chemotherapy and anti-vascular drugs in the first-line or second-line treatment of patients with lung cancer. RESULTS: Three hundred and fifteen patients were enrolled in this study. In patients with stage III-IV adenocarcinoma and Squamous cell carcinoma, the objective response rate (ORR) and disease control rate (DCR) were 35.5% (87/245) and 93.5% (229/245), respectively, the median progression-free survival (PFS) was 10.8 months, and the median overall survival (OS) was not reached. A total of 132 patients received ICIs as the first-line treatment, the median treatment cycle was 8 cycles (2-20 cycles), the short-term efficacy ORR was 38.6%, DCR was 93.9%, and the median PFS was 11.4 months. One hundred thirteen patients received ICIs treatment as second-line treatment, the median treatment cycle was five cycles (2-10 cycles), the short-term efficacy ORR was 31.9%, DCR was 92.9%, and the median PFS was 10.0 months. There were no statistically significant differences in ORR, DCR, or median PFS with ICIs as the first-line treatment compared with the second-line treatment(P > 0.05). The results of subgroup analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), epidermal growth factor receptor (EGFR) mutation status, pathological type and number of treatment lines were not correlated with median PFS(P > 0.05). However, there were statistically significant differences in programmed death-ligand 1(PD-L1) expression, corticosteroid interference, and antibiotic (Abx) treatment among all groups (P < 0.05). In terms of safety, the overall incidence of adverse reactions in 315 patients was 62.5%, and the incidence of immune-related adverse events (irAEs) was 13.7%. Grade 1-2 and 3-4 incidence of adverse events were 34.9 and 27.65%, respectively. There were four patients who experienced fatal irAEs, two cases were liver damage leading to liver failure, one case was immune related pneumonia, and one case was immune related myocarditis. CONCLUSION: In the real world, ICIs has a good effect on patients with lung cancer and significantly improves ORR and PFS.
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Adenocarcinoma , Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/complicações , Análise de Dados , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos RetrospectivosRESUMO
Background: The aim of this study was to build and validate a radiomics nomogram by integrating the radiomics features extracted from the CT images and known clinical variables (TNM staging, etc.) to individually predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC). Methods: A total of 1,480 patients with clinical data and pretreatment CT images during January 2013 and May 2018 were enrolled in this study. We randomly assigned the patients into training (N = 1036) and validation cohorts (N = 444). We extracted 1,288 quantitative features from the CT images of each patient. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was applied in feature selection and radiomics signature building. The radiomics nomogram used for the prognosis prediction was built by combining the radiomics signature and clinical variables that were derived from clinical data. Calibration ability and discrimination ability were analyzed in both training and validation cohorts. Results: Eleven radiomics features were selected by LASSO Cox regression derived from CT images, and the radiomics signature was built in the training cohort. The radiomics signature was significantly associated with NSCLC patients' OS (HR = 3.913, p < 0.01). The radiomics nomogram combining the radiomics signature with six clinical variables (age, sex, chronic obstructive pulmonary disease, T stage, N stage, and M stage) had a better prognostic performance than the clinical nomogram both in the training cohort (C-index, 0.861, 95% CI: 0.843-0.879 vs. C-index, 0.851, 95% CI: 0.832-0.870; p < 0.001) and in the validation cohort (C-index, 0.868, 95% CI: 0.841-0.896 vs. C-index, 0.854, 95% CI: 0.824-0.884; p = 0.002). The calibration curves demonstrated optimal alignment between the prediction and actual observation. Conclusion: The established radiomics nomogram could act as a noninvasive prediction tool for individualized survival prognosis estimation in patients with NSCLC. The radiomics signature derived from CT images may help clinicians in decision-making and hold promise to be adopted in the patient care setting as well as the clinical trial setting.
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INTRODUCTION: This prospective study was designed to determine the prognosis of second molars with external root resorption (ERR-M2s) caused by embedded third molars (EM3s) following EM3 removal and explore related predictors. METHODS: This study consecutively enrolled 58 participants who had asymptomatic second molars with apical external root resorption caused by EM3s. EM3s were extracted, and follow-up examinations were conducted at 1 week, 4 weeks, and 6 months. The primary outcome was prognosis of ERR-M2s after third molar extraction without any further intervention, as assessed via clinical and radiographic examinations. Potential predictors (sex, age, number of roots, EM3s position, type and degree of external root resorption) of prognosis were analyzed via univariable and multivariable analyses. RESULTS: A total of 63 ERR-M2s from 58 patients (16 males and 42 females; 19-57 years of age) were evaluated. At the last follow-up, 56 teeth (89%) remained asymptomatic and normal response to heat and cold tests. According to univariable analyses, ERR-M2s were more likely to remain normal response to heat and cold tests in younger patients. In the multivariable analysis, older age (odds ratio, 1.118; 95% confidence interval, 1.026-1.219; P < .05) and the type of all roots affected (odds ratio, 0.073; 95% confidence interval, 0.007-0.754; P < .05) were significantly associated with poor prognosis. CONCLUSIONS: Asymptomatic ERR-M2s have a high probability of remaining normal pulp without further intervention after EM3 extraction, especially in younger patients. No intervention except follow-up and observation is necessary.