Characteristics of inclusions in chang 7 member and shale oil accumulation stages in Zhijing-Ansai area, Ordos Basin.

In order to further clarify the shale oil accumulation period of the Chang 7 member of the Mesozoic Triassic Yanchang Formation in the Zhijing-Ansai area of the central Ordos Basin, Using fluid inclusion petrography analysis, microscopic temperature measurement, salinity analysis and fluorescence spectrum analysis methods, combined with the burial history-thermal history recovery in the area, the oil and gas accumulation period of the Chang 7 member of the Yanchang Formation in the Zhijing-Ansai area was comprehensively analyzed. Sixteen shale oil reservoir samples of the Mesozoic Triassic Yanchang Formation in seven typical wells in the study area were selected.The results show that the fluid inclusions in the Chang 7 member of Yanchang Formation can be divided into two stages. The first stage inclusions mainly develop liquid hydrocarbon inclusions and a large number of associated brine inclusions, which are mainly beaded in fracture-filled quartz and fracture-filled calcite. The fluorescence color is blue and blue-green, and the homogenization temperature of the associated brine inclusions is between 90-110°C. The second stage inclusions are mainly gas-liquid two-phase hydrocarbon inclusions, gas inclusions and asphalt inclusions. Most of them are distributed in the fracture-filled quartz, and the temperature of the associated brine inclusions is between 120-130°C. Fluid inclusions in Chang 7 member of the Yanchang Formation can be divided into two stages. The CO2 inclusions and high temperature inclusions in the Chang 7 member of the Yanchang Formation are mainly derived from deep volcanic activity in the crust.

Multi-omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma.

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.

Nuclear deformation and cell division of single cell on elongated micropatterned substrates fabricated by DMD lithography.

Cells sense mechanical signals from the surrounding environment and transmit them to the nucleus through mechanotransduction to regulate cellular behavior. Microcontact printing, which utilizes elastomer stamps, is an effective method for simulating the cellular microenvironment and manipulating cell morphology. However, the conventional fabrication process of silicon masters and elastomer stamps requires complex procedures and specialized equipment, which restricts the widespread application of micropatterning in cell biology and hinders the investigation of the role of cell geometry in regulating cell behavior. In this study, we present an innovative method for convenient resin stamp microfabrication based on digital micromirror device planar lithography. Using this method, we generated a series of patterns ranging from millimeter to micrometer scales and validated their effectiveness in controlling adhesion at both collective and individual cell levels. Additionally, we investigated mechanotransduction and cell behavior on elongated micropatterned substrates. We then examined the effects of cell elongation on cytoskeleton organization, nuclear deformation, focal adhesion formation, traction force generation, nuclear mechanics, and the growth of HeLa cells. Our findings reveal a positive correlation between cell length and mechanotransduction. Interestingly, HeLa cells with moderate length exhibit the highest cell division and proliferation rates. These results highlight the regulatory role of cell elongation in mechanotransduction and its significant impact on cancer cell growth. Furthermore, our methodology for controlling cell adhesion holds the potential for addressing fundamental questions in both cell biology and biomedical engineering.

Spinal sirtuin 2 attenuates bone cancer pain by deacetylating FoxO3a.

Bone cancer pain (BCP) is refractory to currently used analgesics. Recently, sirtuin 2 (SIRT2) was reported to play a vital role in neuropathic pain but its role in BCP remains unknown. It was hypothesized that spinal SIRT2 attenuates BCP by deacetylating FoxO3a and suppressing oxidative stress. The mouse model of BCP established by injecting tumor cells into the intramedullary space of the femur demonstrated that spinal SIRT2 and FoxO3a were downregulated in BCP development. Intrathecal administration of LV-SIRT2 reduced pain hypersensitivity (mechanical and thermal nociception) in BCP mice. Spinal SIRT2 overexpression upregulated FoxO3a and antioxidant genes (SOD2 and catalase) and inhibited FoxO3a acetylation, phosphorylation, and ubiquitination. Moreover, intrathecal administration of SIRT2 shRNA induced pain hypersensitivity in normal mice. Spinal SIRT2 knockdown downregulated FoxO3a and antioxidant genes and increased FoxO3a acetylation, phosphorylation, and ubiquitination. In summary, spinal SIRT2 increases FoxO3a expression in BCP mice and inhibits oxidative stress by deacetylating FoxO3a and further reducing FoxO3a phosphorylation, ubiquitination, and degradation, leading to BCP relief.

Experience in the treatment of long-gap esophageal atresia by intraluminal esophageal stretching elongation.

Objective: To summarize the experience with intraluminal esophageal stretching elongation (ILESE) in the successful treatment of long-gap esophageal atresia (LGEA) at a single center. Methods: Clinical data of 68 neonates who underwent LGEA between February 2015 and January 2022 were retrospectively analyzed. Four patients died of multiple associated severe malformations and did not undergo ILESE. Esophageal anastomosis was successfully performed in 60 cases (93.75%) and failed in 4 cases (6.25%) treated with ILESE. The ILESE techniques, esophageal reconstruction, results, postoperative complications, and follow-up treatment were analyzed. Results: The beginning time of performing ILESE preoperation was 53.4 ± 39.4 days after birth, and the age of esophageal reconstruction was 122.2 ± 70.3 days after birth in 60 cases. The gap length of proximal and distal esophageal segments which were evaluated the first time at admission was 4.8 ± 1.3 vertebral bodies, whereas the gap before anastomosis was -0.46 ± 0.90 vertebral bodies. Among the patients with esophageal primary-anastomosis, 55 received thoracoscopic surgery, and 5 underwent thoracotomy in the early stage. Of the 60 children with ILESE, 58 underwent end-to-end esophagostomy, of which 17 cases were combined with circular esophagotomy (livaditis), and 2 cases of esophageal lengthening were combined with the reversal of the ligulate loop of the proximal esophagus (flap). Overall, 59 cases were cured (98.3%), and 1 patient died of respiratory failure postoperatively. All patients were followed up for 7-96 months. Postoperative anastomotic leakage occurred in 16 patients (27.6%), all of whom were successfully treated conservatively. Anastomotic stenosis occurred in 49 cases (83.1%), all of which were successfully managed by non-surgical treatment, including 12.7 ± 9.3 times of esophageal balloon dilatation and 2 cases of stent dilatation. Gastroesophageal reflux occurred in 44 patients (74.6%), including associated or acquired esophageal hiatal hernia in 22 patients, and Nissen fundoplication was performed in 17 patients. Conclusions: ILESE is an effective method for prolonging the proximal and distal esophagus of the LGEA to reconstruct esophageal continuity using its esophageal tissue, with an efficacy rate of 93.75%. Postoperative anastomotic stricture and gastroesophageal reflux are common and require long-term, standardized follow-up and treatment.

Prognostic factors of palatal adenoid cystic carcinoma: A single-center analysis of 85 cases.

Objective: The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. Methods: The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Results: Median follow-up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5-year OS and disease-free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p < .001). Positive margins (p = .001) and high histological grade (p = .031) were significantly associated with shorter OS. Conclusion: Positive surgical margins are a strong adverse prognostic factor affecting LR and OS in patients with ACC; apart from that, high histopathological grade is an independent predictor of poor OS. Level of Evidence: Level 3 (Prognosis - Cohort study).

Performance and Interfacial Microstructure of Al/Steel Joints Welded by Resistance Element Welding.

In this study, an upper sheet of an A6061 aluminum alloy and a lower sheet of Q235 steel were welded by resistance element welding with a steel rivet. The temperature field during welding was calculated using ABAQUS numerical simulation software, and the interfacial microstructure was observed. A nugget was formed between the rivet shank and the lower sheet. With increases in welding current and welding time, the tensile shear load of the joint increased first and then decreased slightly. When the welding current was 14 kA and the welding time was 300 ms, the tensile shear load of the joint reached a maximum of 7.93 kN. The smaller the distance from the position to the lower sheet along the interface between the rivet shank and upper sheet, the longer the high-temperature duration and the higher the peak temperature during welding. At the junction of the rivet shank, upper sheet, and lower sheet in the joint, the high-temperature duration was the longest, at about 392 ms, and the peak temperature was the highest, at about 1237 °C. The results show that the smaller the distance from the position to the lower sheet along the interface between the rivet shank and the upper sheet in the joint, the thicker the reaction layer generated there, and that the thickness of the reaction layer was about 2.0 µm at the junction of the rivet shank, upper sheet, and lower sheet in the joint.

Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney.

The functional and structural changes in the proximal tubule play an important role in the occurrence and development of diabetic kidney disease (DKD). Diabetes-induced metabolic changes, including lipid metabolism reprogramming, are reported to lead to changes in the state of tubular epithelial cells (TECs), and among all the disturbances in metabolism, mitochondria serve as central regulators. Mitochondrial dysfunction, accompanied by increased production of mitochondrial reactive oxygen species (mtROS), is considered one of the primary factors causing diabetic tubular injury. Most studies have discussed how altered metabolic flux drives mitochondrial oxidative stress during DKD. In the present study, we focused on targeting mitochondrial damage as an upstream factor in metabolic abnormalities under diabetic conditions in TECs. Using SS31, a tetrapeptide that protects the mitochondrial cristae structure, we demonstrated that mitochondrial oxidative damage contributes to TEC injury and lipid peroxidation caused by lipid accumulation. Mitochondria protected using SS31 significantly reversed the decreased expression of key enzymes and regulators of fatty acid oxidation (FAO), but had no obvious effect on major glucose metabolic rate-limiting enzymes. Mitochondrial oxidative stress facilitated renal Sphingosine-1-phosphate (S1P) deposition and SS31 limited the elevated Acer1, S1pr1 and SPHK1 activity, and the decreased Spns2 expression. These data suggest a role of mitochondrial oxidative damage in unbalanced lipid metabolism, including lipid droplet (LD) formulation, lipid peroxidation, and impaired FAO and sphingolipid homeostasis in DKD. An in vitro study demonstrated that high glucose drove elevated expression of cytosolic phospholipase A2 (cPLA2), which, in turn, was responsible for the altered lipid metabolism, including LD generation and S1P accumulation, in HK-2 cells. A mitochondria-targeted antioxidant inhibited the activation of cPLA2f isoforms. Taken together, these findings identify mechanistic links between mitochondrial oxidative metabolism and reprogrammed lipid metabolism in diabetic TECs, and provide further evidence for the nephroprotective effects of SS31 via influencing metabolic pathways.

Deep-Learning-Based Nanomechanical Vibration for Rapid and Label-Free Assay of Epithelial Mesenchymal Transition.

Cancer is a profound danger to our life and health. The classification and related studies of epithelial and mesenchymal phenotypes of cancer cells are key scientific questions in cancer research. Here, we investigated cancer cell colonies from a mechanical perspective and developed an assay for classifying epithelial/mesenchymal cancer cell colonies using the biomechanical fingerprint in the form of "nanovibration" in combination with deep learning. The classification method requires only 1 s of vibration data and has a classification accuracy of nearly 92.5%. The method has also been validated for the screening of anticancer drugs. Compared with traditional methods, the method has the advantages of being nondestructive, label-free, and highly sensitive. Furthermore, we proposed a perspective that subcellular structure influences the amplitude and spectrum of nanovibrations and demonstrated it using experiments and numerical simulation. These findings allow internal changes in the cell colony to be manifested by nanovibrations. This work provides a perspective and an ancillary method for cancer cell phenotype diagnosis and promotes the study of biomechanical mechanisms of cancer progression.

Chemically Tailored Single Atoms for Targeted and Light-Controlled Bactericidal Activity.

Single-atom (SA) nanoparticles exhibit considerable potential in terms of photothermal properties for bactericidal applications. Nevertheless, the restricted efficacy of their targeted and controlled antibacterial activity has hindered their practical implementation. This study aims to overcome this obstacle by employing chemical modifications to tailor SAs, thereby achieving targeted and light-controlled antimicrobial effects. By conducting atomic-level modifications on palladium SAs using glutathione (GSH) and mercaptophenylboronic acid (MBA), their superior targeted binding capabilities toward Escherichia coli cells are demonstrated, surpassing those of SAs modified with cysteine (Cys). Moreover, these modified SAs effectively inhibit wound bacteria proliferation and promote wound healing in rats, without inducing noticeable toxicity to major organs under 808 nm laser irradiation. This study highlights the significance of chemical engineering in tailoring the antibacterial properties of SA nanoparticles, opening avenues for combating bacterial infections and advancing nanoparticle-based therapies.

Sole brachytherapy for inoperable, recurrent, and irradiated salivary gland cancer.

BACKGROUND AND PURPOSE: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs. MATERIALS AND METHODS: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated. RESULTS: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events. CONCLUSIONS: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control.

Panax notoginseng saponin R1 improves glucocorticoid-inhibited airway epithelium repair via glucocorticoid receptor ß.

BACKGROUND: Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma. OBJECTIVE: This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma. METHODS: In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRß-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRß-siRNA and detected cell proliferation and migration. The expression of GRß and key components of MKP-1 and Erk1/2 were detected by western blotting. RESULTS: In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRß expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair. CONCLUSIONS: Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRß expression and activating the MAPK pathway.

Platelet membrane-based biochemotactic-targeting nanoplatform combining PDT with EGFR inhibition therapy for the treatment of breast cancer.

Presently, the commonly used anti-tumor drugs lack targeting ability, resulting in a limited therapeutic efficacy and significant side effects. In this view, platelet membranes (PMs) not only exhibit specific binding of its P-selectin protein with CD44, which is highly expressed on breast cancer cells, to promote tumor-active targeting by PM biomimetic nanoplatforms, but also respond to vascular damage, thus inducing biochemotactic targeting to further facilitate the aggregation of these nanoplatforms. Therefore, in this study, a PM was applied to construct a biochemotactic-targeting nanotherapeutic platform based on dendritic large pore mesoporous silica nanoparticles (DLMSNs) co-loaded with chlorin e6 (Ce6) and lapatinib (LAP) to achieve the combination of photodynamic therapy (PDT) and EGFR inhibition therapy for breast cancer. Under laser irradiation, PM@DLMSN/Ce6/Lap could not only effectively kill breast tumor cells by the PDT, but also damage blood vessels. By combining the EGFR inhibition of LAP, PM@DLMSN/Ce6/Lap could better inhibit the migration and movement of tumor cells. In vitro and in vivo results showed that PM@DLMSN/Ce6/Lap could achieve active-targeting drug delivery to breast tumors and further recruit more nanoparticles to accumulate at tumor sites after the PDT-induced damage of blood vessels through biochemotactic targeting, achieving continuous EGFR inhibition to prevent tumor proliferation and metastasis. In conclusion, this study not only provides a new strategy for the clinical treatment of breast cancer, but also provides a design idea for improving the targeted delivery of anti-tumor drugs.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

BACKGROUND: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. METHODS: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. RESULTS: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. CONCLUSIONS: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.

Structurally, FL118 is a camptothecin analogue and possesses exceptional antitumor efficacy against human cancer through a novel mechanism of action (MOA). In this report, we have synthesized and characterized 24 FL118 Position 7-substituted and 24 FL118 Position 9-substituted derivatives. The top compounds were further characterized for their MOA in colorectal cancer (CRC) models using CRC patient-derived xenograft (PDX) models and pancreatic cancer PDX models to evaluate their antitumor activities. Four FL118 Position 7-substituted derivatives showed significantly better antitumor efficacy than the FL118 Position 9-substituted derivatives. The four identified compounds also appeared to have better antitumor activity than their parental platform FL118. Interestingly, RNA-Seq analyses indicated that three of the four compounds exerted antitumor effects via an MOA similar to FL118, which provided an intriguing opportunity for follow-up studies. Extended in vivo studies revealed that FL77-6 (7-(4-ethylphenyl)-FL118), FL77-9 (7-(4-methoxylphenyl)-FL118), and FL77-24 (7-(3, 5-dimethoxyphenyl)-FL118) exhibit potential for further development toward clinical trials.

Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: a real-world retrospective study.

Objectives: The treatment of locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC) is surgery and radiotherapy or chemoradiotherapy but with unsatisfactory survival rate. Neoadjuvant programmed death-1 (PD-1) therapy are being used in several clinical trials. Therefore, in this retrospective study we aimed to determine the feasibility of neoadjuvant tislelizumab plus chemotherapy followed by surgery for LAOOPSCC. Materials and methods: The clinical data of 33 patients with LAOOPSCC who received neoadjuvant PD-1 inhibitors and chemotherapy between April 2021 and October 2022 were retrospectively analyzed. Patients with stage III-IV LAOOPSCC received tislelizumab, albumin-bound paclitaxel, and cisplatin every 3 weeks (Q3W) for two cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. A median follow-up period was 20 months. Results: The objective response rate (ORR) was 66.7%, with the major pathological response (MPR) rate at 54.5%, and the pathological complete response (pCR) rate was 33.3%. Sixteen patients underwent limited surgeries, and 15 patients were remitted from undergoing mandibulectomy and 9 patients were remitted from undergoing near total glossectomy or total glossectomy. A significant difference in the overall survival (OS) and disease-free survival (DFS) was observed in patients who achieved major pathological response (MPR) than who did not. The most common adverse events in neoadjuvant therapy were alopecia, decreased appetite or anorexia, leukopenia, and fatigue. Conclusion: Neoadjuvant PD-1 inhibitors combined with chemotherapy are feasible and safe, with a high pathological response and possible organ preservation in oral or oropharyngeal squamous cell carcinoma. However, further studies with a larger cohort of patients and longer follow-up period is required to strengthen our findings and evaluate the survival benefits of the treatment.

Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment: A Systematic Review and Meta-Analysis.

Importance: Growing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals with cancer who receive immune checkpoint inhibitor (ICI) treatment. Objective: To identify whether the presence of cirAEs and their subtypes subsequent to ICI administration is associated with enhanced cancer prognosis. Data Sources: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications examining the association between cirAE development during ICI treatment and subsequent cancer prognosis. The initial search was limited to English-language publications from database inception until December 31, 2022; a subsequent search was performed on May 21, 2023. Study Selection: Two reviewers independently scrutinized the identical articles and included those that constituted original research evaluating the association between cirAE development and cancer prognosis. Data Extraction and Synthesis: The search terms, study objectives, and methodological protocols were defined before study initiation. The aforementioned 2 reviewers performed data extraction independently and resolved discrepancies through agreement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The protocol was prospectively registered with PROSPERO. Data analyses were conducted between May 21 and June 1, 2023. Main Outcomes and Measures: The major outcome end points were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were also conducted according to cirAE type, cancer type, geographic region, study design, and ICI type. Given the heterogeneity inherent in the included studies, a DerSimonian-Laird random-effects model was adopted. Results: This systematic review and meta-analysis included 23 studies with a total of 22 749 patients treated with ICIs. The occurrence of cirAEs was associated with improved OS (hazard ratio [HR], 0.61 [95% CI, 0.52-0.72]; P < .001) and PFS (HR, 0.52 [95% CI, 0.41-0.65]; P < .001). Consistent results were observed across all subgroups stratified by study design, geographic region, ICI type, and cancer type, aligning with the overall estimate of OS and PFS improvement. However, no statistically significant differences were identified in terms of PFS within studies conducted in the US. Conclusions and Relevance: In this systematic review and meta-analysis, the presence of cirAEs and their subtypes was associated with improved prognosis for individuals with cancer undergoing ICI treatment. These findings suggest that cirAEs may have useful prognostic value in ICI treatment.

Methods of Immobilization after Achilles Tendon Rupture Repair: A Comparative Study in Rat Model.

OBJECTIVE: The Achilles tendon (AT) is the most frequently ruptured in the human body. Literature describing different immobilization methods' impact on tendon healing after AT repair is lacking. We compare plaster cast, splint, and K-wire to determine which is the most stable and has the fewest complications. METHODS: Sixty rats aged 5-6 months were selected to establish Achilles tendon injury in two hind legs model. After suturing the ends of the AT together with a modified "Kessler" method (Prolene 5-0). The skin incision was interrupted and sutured with 1-0 thread. Rats were divided into three immobilization methods (plaster cast group, splint group, and K-wire group). In plaster cast group, the hind leg was cast with plaster in the extended position of the hip and knee joints, and the ankle joint was at 150°. Splint and K-wire group used splints and 0.8-mm K-wires, separately. The fixed period was 4 weeks. The incidence of stability and complications (death, necrosis of the legs, necrosis of the skin, and incisional infection) were recorded. Differences were detected using the chi-square test. RESULTS: Within 4 weeks observation, K-wires showed better stability (90%) compared with the other two ways (40% in plaster cast group, 65% in splint group; p < 0.05). Rats immobilized with K-wires (10%) suffered significantly lower complications compared with plaster cast and splint group (15%; p < 0.05). CONCLUSION: K-wire has better stability, lower complication rate than other methods. Immobilization with K-wire may be a promising tool in future clinical Achilles tendon rupture applications.

Postoperative intraocular lens stability following cataract surgery with or without primary posterior continuous curvilinear capsulorrhexis: an intra-individual randomized controlled trial.

PURPOSE: To evaluate the effect of primary posterior continuous curvilinear capsulorrhexis (PPCCC) on the positional stability of IOLs. METHODS: This study is a prospective intra-individual comparative randomized controlled trial including 31 patients (62 eyes). Eyes of the same patient were randomly assigned to the PPCCC group (18 right eyes and 13 left eyes) or group without PPCCC (NPCCC group). Eyes in both groups were implanted with a one-piece foldable hydrophobic acrylic IOL via routine cataract surgery. Patients in the PPCCC group underwent additional manual PPCCC before IOL implantation. Examinations were performed 1 day, 1 week, 1 month and 3 months postoperatively. IOL tilt (x, y), decentration (x, y), anterior chamber depth (z) and refractive prediction error data were collected and analyzed with Pentacam. RESULTS: Postoperatively, the range of IOL position change over 3 months in PPCCC group was comparable to NPCCC group, which indicated smaller value in every tilt and decentration index. PPCCC eyes showed comparable tilt and decentration with NPCCC eyes in this study endpoint: mean tilt (x, y), decentration (x, y) and anterior chamber depth (ACD) were 1.04 ± 0.56°, 0.90 ± 0.64°, 0.239 ± 0.140 mm, 0.233 ± 0.133 mm and 4.01 ± 0.32 mm, respectively, in the PPCCC group vs. 1.09 ± 0.76°, 1.10 ± 0.82°, 0.252 ± 0.153 mm, 0.244 ± 0.155 mm and 4.01 ± 0.38 mm, respectively, in the NPCCC group. Refractive prediction error in the PPCCC group demonstrated a mild hyperopic shift vs. the NPCCC group (0.13 ± 0.50 vs. 0.05 ± 0.39; p = 0.208), and corrected distance visual acuity (CDVA) did not differ between the two groups (0.027 ± 0.014 vs. 0.059 ± 0.185; p = 0.377). CONCLUSIONS: Comparable IOL tilt, decentration, ACD and refractive prediction error were observed in PPCCC eyes with that underwent routine cataract surgery. Little IOL position fluctuation and good visual acuity were shown in PPCCC group over time. TRAIL REGISTRATION: The study was registered at the Chinese Clinical Trial Register Center on May 27th, 2020 (protocol code ChiCTR2000033304, 27/05/2020).