OBJECTIVES: To construct a nomogram for predicting the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (aNSCLC) by integrating chest CT radiomics signature that reflects the tumor microenvironment (TME) and clinical parameters of the patients. METHODS: Transcriptomic and CT imaging data from TCGA, GEO and TCIA databases were integrated for weighted gene co-expression network analysis (WGCNA) of the GEO cohort to identify the immunotherapy-related genes (IRGs) associated with ICIs response. A prognostic model was built using these IRGs in the TCGA cohort to assess immune microenvironment features across different risk groups. Radiomics features were extracted from TCIA lung_3 cohort using PyRadiomics, and 94 features showing strong association with IRGs (|r|>0.4) were selected. A retrospective cohort consisting of 210 aNSCLC patients receiving first-line ICIs at Guangdong Provincial People's Hospital was analyzed and divided into training (n=147) and validation (n=63) groups. Least absolute shrinkage and selection operator was used for radiomic features selection, and logistic regression was applied to construct a combined clinical-radiomic model and nomogram for predicting ICIs therapy response. The performance of the model was evaluated using ROC curve, calibration curve, and decision curve analysis. RESULTS: WGCNA identified 84 IRGs enriched in immune activation pathways. The combined model outperformed individual models in both the training (AUC=0.725, 95% CI: 0.644-0.807) and validation cohorts (AUC=0.706, 95% CI: 0.577-0.836). Calibration curve and decision curve analyses confirmed the clinical efficacy of the nomogram for predicting ICIs therapy response in aNSCLC patients. CONCLUSIONS The genomic-radiomic-clinical multidimensional predictive framework established in this study provides an interpretable biomarker combination and clinical decision-making tool for evaluating ICIs efficacy in aNSCLC, potentially facilitating personalized immunotherapy decision-making.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Tumor Microenvironment ; Lung Neoplasms/therapy* ; Immunotherapy ; Tomography, X-Ray Computed ; Nomograms ; Retrospective Studies ; Immune Checkpoint Inhibitors/therapeutic use* ; Prognosis ; Male ; Female ; Radiomics

Objective To explore the identification of adverse reactions of type 1 diabetes during lung cancer treat-ment with cardonilimab and the pharmaceutical monitoring of patient's blood glucose management,and to accumulate ex-perience for the prevention,treatment,and pharmaceutical services of related diseases.Methods The clinical pharmacist assisted doctors in judging adverse drug reactions and identifying suspicious drugs in a patient with lung cancer who devel-oped type 1 diabetes.At the same time,the clinical pharmacist provided suggestions for clinical treatment by referring to clinical evidence,and providing medication education,pharmaceutical care,and long-term follow-up for the patient's blood glucose management.Results After intensive insulin therapy and dietary control,the patient's high glucose symptoms were relieved,and the blood glucose gradually stabilized.The patient continued to be challenged using cardonilimab immu-notherapy,and the condition was stable.Conclusions Clinical pharmacists assist physicians in identifying adverse drug reactions on time and participate in the full process management of patient medication.They play an active therapeutic role in the medical team and reflect the value of pharmaceutical services.

Objective:To explore the effects of vitamin D supplementation combined with suspended lumbar abdominal muscle training on rehabilitation and bone metabolism indexes of patients after OVCF.Methods:A total of 140 patients with osteoporotic vertebral compression fractures (OVCF) treated at Yantaishan Hospital from Jun. 2021 to Jun. 2024 were included in this study. Patients were randomly assigned to a control group and an observation group using a random number table, with 70 patients in each group. The control group received suspension lumbar and abdominal muscle training, while the observation group received vitamin D supplementation combined with suspension lumbar and abdominal muscle training. Outcomes evaluated included VAS scores, Oswestry Disability Index (ODI) , Cobb Angle, lumboabdominal muscle strength, and serum levels of 25-hydroxyvitamin D [25 (OH) D], bone mineral density T value, and bone metabolism markers [serum osteocalcin (OC) , calcitonin (CT) , total type I collagen amino-terminal propeptide (tPINP) , type I collagen carboxy-terminal peptide β special sequence (β-CTX) , intact parathyroid hormone (iPTH) , and bone-specific alkaline phosphatase (BALP) ] measured by chemiluminescence.Results:In comparison with the control group, the VAS and ODI scores in the observation group were lower after treatment ( t=13.66, t=9.87, P < 0.05) . Compared to the control group, the lumbar muscle strength score of the observation group, the 25 (OH) D level and bone mineral density T value was higher after treatment ( t=57.63, t=6.64, t=5.01, P < 0.05) , and the Cobb Angle was smaller ( t=9.21, P < 0.05) .Compared with the control group, the bone metabolism indexes OC, CT, tPINP, and BALP were higher in the observation group after treatment ( t=4.21, t=3.05, t=2.66, t=3.16, P < 0.05) , while the iPTH and β-CTX were lower ( t=7.28, t=3.50, P < 0.05) . Conclusions:Vitamin D supplementation combined with suspended lumbar and abdominal muscle training can promote postoperative rehabilitation of OVCF patients and improve the level of bone metabolism indexes after surgery.

Objective:To explore the effects of vitamin D supplementation combined with suspended lumbar abdominal muscle training on rehabilitation and bone metabolism indexes of patients after OVCF.Methods:A total of 140 patients with osteoporotic vertebral compression fractures (OVCF) treated at Yantaishan Hospital from Jun. 2021 to Jun. 2024 were included in this study. Patients were randomly assigned to a control group and an observation group using a random number table, with 70 patients in each group. The control group received suspension lumbar and abdominal muscle training, while the observation group received vitamin D supplementation combined with suspension lumbar and abdominal muscle training. Outcomes evaluated included VAS scores, Oswestry Disability Index (ODI) , Cobb Angle, lumboabdominal muscle strength, and serum levels of 25-hydroxyvitamin D [25 (OH) D], bone mineral density T value, and bone metabolism markers [serum osteocalcin (OC) , calcitonin (CT) , total type I collagen amino-terminal propeptide (tPINP) , type I collagen carboxy-terminal peptide β special sequence (β-CTX) , intact parathyroid hormone (iPTH) , and bone-specific alkaline phosphatase (BALP) ] measured by chemiluminescence.Results:In comparison with the control group, the VAS and ODI scores in the observation group were lower after treatment ( t=13.66, t=9.87, P < 0.05) . Compared to the control group, the lumbar muscle strength score of the observation group, the 25 (OH) D level and bone mineral density T value was higher after treatment ( t=57.63, t=6.64, t=5.01, P < 0.05) , and the Cobb Angle was smaller ( t=9.21, P < 0.05) .Compared with the control group, the bone metabolism indexes OC, CT, tPINP, and BALP were higher in the observation group after treatment ( t=4.21, t=3.05, t=2.66, t=3.16, P < 0.05) , while the iPTH and β-CTX were lower ( t=7.28, t=3.50, P < 0.05) . Conclusions:Vitamin D supplementation combined with suspended lumbar and abdominal muscle training can promote postoperative rehabilitation of OVCF patients and improve the level of bone metabolism indexes after surgery.

Objective To explore the identification of adverse reactions of type 1 diabetes during lung cancer treat-ment with cardonilimab and the pharmaceutical monitoring of patient's blood glucose management,and to accumulate ex-perience for the prevention,treatment,and pharmaceutical services of related diseases.Methods The clinical pharmacist assisted doctors in judging adverse drug reactions and identifying suspicious drugs in a patient with lung cancer who devel-oped type 1 diabetes.At the same time,the clinical pharmacist provided suggestions for clinical treatment by referring to clinical evidence,and providing medication education,pharmaceutical care,and long-term follow-up for the patient's blood glucose management.Results After intensive insulin therapy and dietary control,the patient's high glucose symptoms were relieved,and the blood glucose gradually stabilized.The patient continued to be challenged using cardonilimab immu-notherapy,and the condition was stable.Conclusions Clinical pharmacists assist physicians in identifying adverse drug reactions on time and participate in the full process management of patient medication.They play an active therapeutic role in the medical team and reflect the value of pharmaceutical services.

White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.
Humans ; Depressive Disorder, Major/pathology* ; White Matter/pathology* ; Male ; Female ; Support Vector Machine ; Adult ; Magnetic Resonance Imaging ; Middle Aged ; Case-Control Studies ; Sensorimotor Cortex ; Brain

BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Three hundred and twenty endophytic actinobacterial strains were isolated from psammophytes collected from Taklamakan Desert and identified.Among them,three strains already had been identified as new species of two genera and sixteen isolates showed relatively low 16S rRNA similarities＜98.6％to validly described species.Seventy-five of the isolates were selected as representative strains to screen antibacterial activity and mechanism.Forty-seven strains showed antagonistic activity against at least one of the indicator bacteria.Two Streptomyces strains produced bioactive compounds inducing DNA damage,and two Streptomyces strains produced bioactive compounds with inhibitory activity on protein biosynthesis.Notably,the strain Streptomyces sp.8P21H-1 that demonstrated both strong antibacterial activity and inhibitory activity on protein biosynthesis was prioritized for exploring new antibiotics.Under the strategy of integrating genetics-based discovery program and MS/MS-based molecular networking,two new streptogramin-type antibiotics,i.e.,acetyl-griseoviridin and desulphurizing gri-seoviridin,along with known griseoviridin,were isolated from the culture broth of strain 8P21H-1.Their chemical structures were determined by HR-MS,and 1D and 2D NMR.Desulphurizing griseoviridin and griseoviridin exhibited antibacterial activities by inhibiting translation.

Objective:To explore the correlations of α-melanocyte stimulating hormone ( α-MSH) levels in serum and synovial fluid with progression of primary knee osteoarthritis (KOA). Methods:A retrospective analysis was conducted of the 96 patients who had been diagnosed as primary KOA at Department of Orthopedics, The First Hospital of Huizhou from October 2018 to October 2019. Radiographic severity of KOA was determined by Kellgren-Lawrence (K-L) grades; α-MSH levels were measured by enzyme-linked immunosorbent assay (ELISA). Levels of pro-inflammatory cytokine interleukin-1 β (IL-1 β) and matrix metalloproteinase-3 (MMP-3) were also detected. Another 64 patients with patellar dislocation, matched in age and gender, were enrolled as controls. The Numeric Pain Scale (NPS) and revised Oxford Knee Score (OKS) were employed to evaluate their symptomatic severity. Receiver operating characteristics (ROC) curve was used to compare α-MSH, IL-1 β and MMP-3 with regard to their diagnostic values in the K-L grading. Results:There were no statistically significant difference in age, gender and body mass index between the 2 groups, showing they were comparable ( P> 0.05). The α-MSH levels in synovial fluid were significantly lower in the KOA patients than in the controls [(16.9±3.8) pg/mL versus (18.8±2.7) pg/mL] ( P<0.001); there were no significant differences between the KOA patients and the controls in the serum α-MSH levels [(24.9±1.8) pg/mL versus (24.8±1.7) pg/mL] ( P>0.05). The α-MSH levels in synovial fluid were negatively correlated with K-L grades ( r=-0.382, P<0.001) and negatively correlated with NPS ( r=-0.382, P<0.001) but positively correlated with OKS ( r=0.339, P<0.001). Moreover, the α-MSH levels in synovial fluid were negatively correlated with the IL-1 β levels in synovial fluid ( r=-0.483, P<0.001) and with the MMP-3 levels in synovial fluid ( r=-0.336, P< 0.001). Conclusions:The level of serum α-MSH may not be correlated with the progression of KOA but the synovial fluid α-MSH is negatively correlated with the progression of KOA. Therefore, the expression level of α-MSH in joint synovial fluid can be used as a potential biomarker for assessment of severity of knee osteoarthritis.

Extralevator abdominoperineal excision (ELAPE) has been suggested to potentially improve oncological outcomes in advanced low rectal cancer patients. However, the urogenital function impairment as one of the main complications deteriorates the quality of life in these patients. The key point to prevent urogenital function impairment is to avoid autonomic nerve injury, including the superior and inferior hypogastric nerve plexus and neurovascular bundle. Three areas should be especially focused during surgery, including the posterolateral aspect of the prostate during the separation of the rectum from prostate, the lateral wall of ischioanal fossa and the area in front of anal canal. Previous presumption supposed that extended resection, though promoting oncologic outcomes, might lead to enlarged injury to surrounding vessels and nerves that deteriorated patients′ urogenital function. But recent studies show that postoperative urogenital function outcomes of rectal cancer patients who underwent ELAPE are not inferior to conventional APE after the induction of minimal invasive approaches including laparoscopic and robotic surgery. Their quality of life can be comparable with patients who underwent conventional APE, and are even better in some particular area. Moreover, as further improvement of ELAPE procedure has been made, the concept of individualized ELAPE addressed the importance of personalized surgical procedure based on tumor stage and location, dedicating to avoid injury to vessels and nerves through preserving more surrounding tissues. Urogenital function outcomes, as part of postoperative outcomes, get more and more attention in recent years. We review current studies on urogenital function after ELAPE from anatomy to clinical research, in order to raise surgeons′ attention of nerve preservation technique and to improve their understanding of ELAPE procedure.