Single-arm study of camrelizumab plus apatinib for patients with advanced mucosal melanoma.

BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers. METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR). RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response. CONCLUSION: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023277.

Tunable thermoresponsive hydrogels for temperature regulation and warning in fruit and vegetables preservation.

Fresh fruit and vegetables usually suffer from quality deterioration when exposed to inappropriate temperatures. Common energy-input temperature regulation is widely applied but there remain challenges of increasing energy consumption. Passive temperature management regulates the heat transfer without energy consumption, showing a sustainable strategy for food preservation. Here, thermoresponsive hydrogels were constructed by incorporating NaCl and sodium dodecyl sulfate (SDS) micelles into a poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-co-AM)) network. Due to the excellent mechanical properties and reversible thermochromism at 14 °C and 37 °C, Gel-8 wt%-NaCl could inhibit temperature rise and avoid sunburn damage to peppers under direct sunlight by blocking the input of solar energy and accelerating moisture evaporation. Additionally, hydrogels could act as a feasible sensor by providing real-time visual warnings for inappropriate temperatures during banana storage. Based on the self-adaptive thermoresponsive behaviour, the prepared hydrogels showed effective performance of temperature regulation and quality preservation of fruit and vegetables.

Pt/Al2O3@Ce/ZrO2-S bifunctional catalysts prepared by mechanically milling for selective catalytic oxidation of high-concentration ammonia.

The selective catalytic oxidation (SCO) is an effective method for removing slipped high-concentration ammonia from NH3-fueled engine exhaust gas. Herein a novel bifunctional catalyst was synthesized by mechanically mixing sulfated Ce/ZrO2 (Ce/ZrO2-S) with a small fraction of Pt/Al2O3 (Pt 0.1 wt.%) for SCO of NH3. As expected, the introduction of a small amount of Pt/Al2O3 significantly improved NH3 conversion ability of Ce/ZrO2-S catalysts toward low-temperature direction. When the mass ratio of Pt/Al2O3 to Ce/ZrO2-S was 7.5% (the corresponding mixed catalyst was denoted as P@CZS-7.5), T90 temperature was 312 °C. More importantly, P@CZS-7.5 catalyst exhibited a much better N2 selectivity (> 96%) in a wide temperature range (320 ~ 450 °C). H2-TPR results revealed that the addition of a trace amount of Pt/Al2O3 significantly led to a distinct shift of reduction temperature peak toward low-temperature direction, thereby greatly improved the low-temperature redox performance of mixed catalysts. Furthermore, NH3-TPD and BET results showed that P@CZS-7.5 catalyst exhibited a similar NH3 adsorption capacity to Ce/ZrO2-S catalyst, while the former had a relatively higher specific surface area than the latter. It was considered as a crucial factor for P@CZS-7.5 catalyst maintaining superior N2 selectivity in high-concentration NH3 (5000 ppm) removal processes. In situ DRIFTS results indicated that P@CZS-7.5 catalyst followed the internal selective catalytic reduction (i-SCR) mechanism in NH3-SCO reactions.

D-mannose alleviates intervertebral disc degeneration through glutamine metabolism.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. METHODS: The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. RESULTS: In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. CONCLUSIONS: In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.

SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1ß pathway.

Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

MiRNA-192-5p-targeted activated leukocyte cell adhesion molecule improved inflammatory injury of neonatal necrotizing enterocolitis.

BACKGROUND: Neonatal necrotizing enterocolitis (NEC) is a common gastrointestinal emergency in neonates. MiRNA-192-5p was found associated with ulcerative colitis (UC) progression, also with aberrant expression in intestinal cancer tissue. However, the effects of miRNA-192-5p on NEC have not been reported. METHODS: Based on the bioinformatics analysis of the GEO dataset, miR-192-5p was identified as the differentially expressed miRNA in NEC, and activated leukocyte cell adhesion molecule (ALCAM) was predicted as its target. After that, in vitro, rat intestinal epithelial cell-6 (IEC-6) were stimulated with LPS to construct a cell model of NEC. IEC-6 cells were transfected with miRNA-192-5p mimics, miRNA-192-5p inhibitors, or miRNA-192-5p inhibitors + sh-ALCAM, and relevant negative control. In vivo, SD rats were treated with artificial feeding, hypoxic reoxygenation, cold stimulation, and LPS gavage to induce NEC, followed by injection of agomiR-NC or agomiRNA-192-5p. Then effects of miRNA-192-5p on NEC model IEC-6 cell viability, apoptosis, ALCAM expression, Interleukin (IL)-1ß and IL-6 levels, intestinal injury, intestinal permeability were detected. RESULTS: MiRNA-192-5p expression was downregulated in NEC IEC-6 cells, whose overexpression increased IEC-6 cell viability. MiRNA-192-5p inhibitors increased IL-1ß, IL-6 levels and promoted IEC-6 cell apoptosis. MiRNA-192-5p targeting of ALCAM decreased ALCAM expression, IL-1ß, and IL-6 levels. AgomiRNA-192-5p decreased ALCAM, IL-1ß, and IL-6 levels in intestinal tissue and pathological damage and increased miRNA-192-5p levels. CONCLUSION: MiR-192-5p protects against intestinal injury by inhibiting ALCAM-mediated inflammation and intestinal epithelial cells, which would provide a new idea for NEC treatment.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

Motor symptoms of Parkinson's disease are affected by temperature: A controlled pilot study.

PURPOSE: The motor symptoms (MS) of Parkinson's disease (PD) have been affecting the quality of life in patients. In clinical practice, most patients with PD report that MS are more severe in winter than in summer, and hyperthermic baths (HTB) could temporarily improve MS. The study aimed to evaluate the effects of seasonal variation and aquatic thermal environment of HTB on the MS of PD. PATIENTS AND METHODS: A cross-sectional study of 203 Chinese Han patients was performed. Univariate and multivariate analyses were performed to analyze seasonal variation in MS relative to baseline data (sex, age at onset, duration, season of birth, Hoehn and Yahr stage, family history, levodopa equivalent dose, and the effect of HTB on MS). Ten subjects participated in the HTB study, and one patient dropped out. The paired Wilcoxon rank test was used to assess the differences in the Movement Disorder Society-United Parkinson's disease Rating Scale (MDS-UPDRS) part III motor examination total scores and the modified Webster Symptoms Score between non-HTB and before HTB and between non-HTB and after HTB. RESULTS: The improvement of MS after HTB was an independent risk factor for seasonal variation in MS (OR, 25.203; 95% CI, 10.951-58.006; p = .000). Patients with PD had significant improvements in the MDS-UPDRS part III motor examination total scores, especially in bradykinesia (p = .043), rigidity (p = .008), posture (p = .038), and rest tremor amplitude (p = .047). CONCLUSION: Seasonal variation in temperature and water temperature of HTB may affect MS in some patients with PD. Simple HTB could be recommended as physiotherapy for patients with PD who report temperature-sensitive MS.

The differential computed tomography features between small benign and malignant solid solitary pulmonary nodules with different sizes.

Background: Computed tomography (CT) has been widely known to be the first choice for the diagnosis of solid solitary pulmonary nodules (SSPNs). However, the smaller the SSPN is, the less the differential CT signs between benign and malignant SSPNs there are, which brings great challenges to their diagnosis. Therefore, this study aimed to investigate the differential CT features between small (≤15 mm) benign and malignant SSPNs with different sizes. Methods: From May 2018 to November 2021, CT data of 794 patients with small SSPNs (≤15 mm) were retrospectively analyzed. SSPNs were divided into benign and malignant groups, and each group was further classified into three cohorts: cohort I (diameter ≤6 mm), cohort II (6 mm < diameter ≤8 mm), and cohort III (8 mm < diameter ≤15 mm). The differential CT features of benign and malignant SSPNs in three cohorts were identified. Multivariable logistic regression analyses were conducted to identify independent factors of benign SSPNs. Results: In cohort I, polygonal shape and upper-lobe distribution differed significantly between groups (all P<0.05) and multiparametric analysis showed polygonal shape [adjusted odds ratio (OR): 12.165; 95% confidence interval (CI): 1.512-97.872; P=0.019] was the most effective variation for predicting benign SSPNs, with an area under the receiver operating characteristic curve (AUC) of 0.747 (95% CI: 0.640-0.855; P=0.001). In cohort II, polygonal shape, lobulation, pleural retraction, and air bronchogram differed significantly between groups (all P<0.05), and polygonal shape (OR: 8.870; 95% CI: 1.096-71.772; P=0.041) and the absence of pleural retraction (OR: 0.306; 95% CI: 0.106-0.883; P=0.028) were independent predictors of benign SSPNs, with an AUC of 0.778 (95% CI: 0.694-0.863; P<0.001). In cohort III, 12 CT features showed significant differences between groups (all P<0.05) and polygonal shape (OR: 3.953; 95% CI: 1.508-10.361; P=0.005); calcification (OR: 3.710; 95% CI: 1.305-10.551; P=0.014); halo sign (OR: 6.237; 95% CI: 2.838-13.710; P<0.001); satellite lesions (OR: 6.554; 95% CI: 3.225-13.318; P<0.001); and the absence of lobulation (OR: 0.066; 95% CI: 0.026-0.167; P<0.001), air space (OR: 0.405; 95% CI: 0.215-0.764; P=0.005), pleural retraction (OR: 0.297; 95% CI: 0.179-0.493; P<0.001), bronchial truncation (OR: 0.165; 95% CI: 0.090-0.303; P<0.001), and air bronchogram (OR: 0.363; 95% CI: 0.208-0.633; P<0.001) were independent predictors of benign SSPNs, with an AUC of 0.869 (95% CI: 0.840-0.897; P<0.001). Conclusions: CT features vary between SSPNs with different sizes. Clarifying the differential CT features based on different diameter ranges may help to minimize ambiguities and discriminate the benign SSPNs from malignant ones.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Variability in Leaf Color Induced by Chlorophyll Deficiency: Transcriptional Changes in Bamboo Leaves.

The diversity of leaf characteristics, particularly leaf color, underscores a pivotal area of inquiry within plant science. The synthesis and functionality of chlorophyll, crucial for photosynthesis, largely dictate leaf coloration, with varying concentrations imparting different shades of green. Complex gene interactions regulate the synthesis and degradation of chlorophyll, and disruptions in these pathways can result in abnormal chlorophyll production, thereby affecting leaf pigmentation. This study focuses on Bambusa multiplex f. silverstripe, a natural variant distinguished by a spectrum of leaf colors, such as green, white, and green-white, attributed to genetic variations influencing gene expression. By examining the physiological and molecular mechanisms underlying chlorophyll anomalies and genetic factors in Silverstripe, this research sheds light on the intricate gene interactions and regulatory networks that contribute to leaf color diversity. The investigation includes the measurement of photosynthetic pigments and nutrient concentrations across different leaf color types, alongside transcriptomic analyses for identifying differentially expressed genes. The role of key genes in pathways such as ALA biosynthesis, chlorophyll synthesis, photosynthesis, and sugar metabolism is explored, offering critical insights for advancing research and plant breeding practices.

Clinical and non-contrast computed tomography characteristics and disease development in patients with benign pulmonary subsolid nodules with a solid component ≤ 5 mm.

OBJECTIVES: To evaluate the clinical and non-contrast computed tomography (CT) features of patients with benign pulmonary subsolid nodules (SSNs) with a solid component ≤ 5 mm and their development trends via follow-up CT. METHODS: We retrospectively collected 436 data from patients who had SSNs with a solid component ≤ 5 mm, including 69 with absorbable benign SSNs (AB-SSNs), 70 with nonabsorbable benign SSNs (NB-SSNs), and 297 with malignant SSNs (M-SSNs). Models 1, 2, and 3 for distinguishing the different types of SSNs were then developed and validated. RESULTS: Patients with AB-SSNs were younger and exhibited respiratory symptoms more frequently than those with M-SSNs. The frequency of nodules detected during follow-up CT was in the following order: AB-SSNs > NB-SSNs > M-SSNs. NB-SSNs were smaller than M-SSNs, and ill-defined margins were more frequent in AB-SSNs than in NB-SSNs and M-SSNs. Benign SSNs exhibited irregular shape, target sign, and lower CT values more frequently compared to M-SSNs, whereas the latter demonstrated bubble lucency more commonly compared to the former. Furthermore, AB-SSNs showed more thickened interlobular septa and satellite lesions than M-SSNs and M-SSNs had more pleural retraction than AB-SSNs (all p < 0.017). The three models had AUCs ranging 0.748-0.920 and 0.790-0.912 in the training and external validation cohorts, respectively. A follow-up CT showed nodule progression in four benign SSNs. CONCLUSIONS: The three SSN types have different clinical and imaging characteristics, with some benign SSNs progressing to resemble malignancy. CRITICAL RELEVANCE STATEMENT: A good understanding of the imaging features and development trends of benign SSNs may help reduce unnecessary follow-up or interventions. This retrospective study explores the CT characteristics of benign SSNs with a solid component ≤ 5 mm by comparing AB-SSNs, NB-SSNs, and M-SSNs and delineates their development trends via follow-up CT. KEY POINTS: 1. Different subsolid nodule types exhibit distinct clinical and imaging features. 2. A miniscule number of benign subsolid nodules can progress to resemble malignancy. 3. Knowing the clinical and imaging features and development trends of benign subsolid nodules can improve management.

Meckel's diverticulum mimicking acute appendicitis in children: a retrospective cohort study.

BACKGROUND: The aims of this study were to summarize the clinical presentation and histological results of 20 cases of complicated Meckel diverticulum (MD) who were presumed to have acute appendicitis before surgery, as well as to improve the diagnosis and treatment of complicated MD in children. MATERIALS AND METHODS: We retrospectively reviewed the records of 20 complicated MD admitted to our institution who were preoperatively diagnosed with acute appendicitis from January 2012 to January 2019. Patients were divided into the perforated MD group and the Meckel's diverticulitis group. Patient demographics, clinical manifestations, laboratory data, auxiliary examinations, surgical methods, and the result of heterotopic tissue were recorded. RESULTS: A total of 20 cases of complicated MD (perforated or diverticulitis) were identified. Children were aged from 3 to 13 years, with a mean age of 7.75 years (median 7.75; range, 1-13 years). Perforated Meckel's diverticulum occurred in 5 of 20 (25%) cases. For perforated MD versus diverticulitis, no significant differences were found between age, time to intervention, length of hospital stay, and distance from the ileo-cecal valve. Heterotopic tissue was confirmed on histopathology in 75% of all patients, including 10 cases of gastric mucosa, 3 cases of coexistent gastric mucosa and pancreatic tissue, and 2 cases of pancreatic tissue. All patients underwent diverticulectomy or partial ileal resection under laparoscopy or laparotomy; two cases combined with appendectomy owing to slight inflammation of the appendix. CONCLUSIONS: The most common presentation of symptomatic MD is painless rectal bleeding; however, it can present symptoms of acute abdomen mimicking acute appendicitis. The key point of diverticulectomy is to remove the ectopic mucosa completely.

Clinical study of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma.

Herein, we aimed to evaluate the efficacy and safety of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma (OSCC). Fifty-one patients with OSCC, treated from July 2020 to October 2022, were analyzed. Of them, 41 patients underwent surgery 4-8 weeks after undergoing two cycles of camrelizumab (200 mg IV Q3W) combined with docetaxel (75 mg/m2 IV Q3W) and carboplatin (area under the curve = 5-6 IV Q3W). The primary endpoint was the pathological complete response rate. All 51 patients (100%) experienced treatment-related grades 1-2 adverse events, and 2 patients (3.9%) experienced grade 4 events (including elevated alanine transaminase/aspartate transferase levels and Guillain-Barre syndrome). Fifty patients were evaluated for the treatment efficacy. Of them, 13 achieved complete response, and the objective response rate was 74%. Only 41 patients underwent surgical treatment. The pathological complete response rate was 17.1%, the major pathological response rate was 63.4%, and the R0 resection rate was 100%. Approximately 22% of the patients had tumor regression grades 0. Eight patients (19.5%) developed surgery-related complications. The median follow-up time was 18 months (range: 3-29 months). Four patients experienced disease progression, while four died. The median disease-free survival and overall survival were not reached. Camrelizumab combined with docetaxel and carboplatin is an effective and safe neoadjuvant treatment for locally advanced OSCC. This regimen may afford a potential strategy to treat patients with locally advanced OSCC.

Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis / 中华儿科杂志

Objective: To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH). Methods: This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children's hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate. Results: Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive. Conclusions: For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Identification and characterization of the cupin_1 domain-containing proteins in ma bamboo (Dendrocalamus latiflorus) and their potential role in rhizome sprouting.

Cupin_1 domain-containing protein (CDP) family, which is a member of the cupin superfamily with the most diverse functions in plants, has been found to be involved in hormone pathways that are closely related to rhizome sprouting (RS), a vital form of asexual reproduction in plants. Ma bamboo is a typical clumping bamboo, which mainly reproduces by RS. In this study, we identified and characterized 53 Dendrocalamus latiflorus CDP genes and divided them into seven subfamilies. Comparing the genetic structures among subfamilies showed a relatively conserved gene structure within each subfamily, and the number of cupin_1 domains affected the conservation among D. latiflorus CDP genes. Gene collinearity results showed that segmental duplication and tandem duplication both contributed to the expansion of D. latiflorus CDP genes, and lineage-specific gene duplication was an important factor influencing the evolution of CDP genes. Expression patterns showed that CDP genes generally had higher expression levels in germinating underground buds, indicating that they might play important roles in promoting shoot sprouting. Transcription factor binding site prediction and co-expression network analysis indicated that D. latiflorus CDPs were regulated by a large number of transcription factors, and collectively participated in rhizome buds and shoot development. This study significantly provided new insights into the evolutionary patterns and molecular functions of CDP genes, and laid a foundation for further studying the regulatory mechanisms of plant rhizome sprouting.

Solitary lung adenocarcinoma: follow-up CT, pathological-molecular characteristics, and surgical prognosis for different morphological classifications.

OBJECTIVE: To investigate the dynamic changes during follow-up computed tomography (CT), histological subtypes, gene mutation status, and surgical prognosis for different morphological presentations of solitary lung adenocarcinomas (SLADC). MATERIALS AND METHODS: This retrospective study compared dynamic tumor changes and volume doubling time (VDT) in 228 patients with SLADC (morphological types I-IV) who had intermittent growth during follow-ups. The correlation between the morphological classification and histological subtypes, gene mutation status, and surgical prognosis was evaluated. RESULTS: Among the 228 patients, 66 (28.9%) were classified as type I, 123 (53.9%) as type II, 16 (7%) as type III, and 23 (10.1%) as type IV. Type I had the shortest VDT (254 days), followed by types IV (381 days) and III (501 days), and then type II (993 days) (p < 0.05 each). Type I had a greater proportion of solid/micropapillary-predominant pattern than type II, and the lepidic-predominant pattern was more common in type II and III than in type I (p < 0.05 each). Furthermore, type II and IV SLADCs were correlated with positive epidermal growth factor receptor mutation (p < 0.05 each). Lastly, the Kaplan-Meier curves showed that the disease-free survival was longest for patients with type II tumors, followed by those with type III and IV tumors, and then those with type I tumors (p < 0.001 each). CONCLUSION: A good understanding of the natural progression and pathological-molecular characteristics of different morphological SLADC types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes. CRITICAL RELEVANCE STATEMENT: A good understanding of the natural progression and pathological-molecular characteristics of different morphological solitary lung adenocarcinoma types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes. KEY POINTS: • Type I-IV solitary lung adenocarcinomas exhibit varying natural progression on serial CT scans. • Morphological classification of solitary lung adenocarcinomas predicts histological subtype, gene status, and surgical prognosis. • This classification of solitary lung adenocarcinomas may help improve diagnostic, therapeutic, and prognosticating abilities.