Catalyst-Free, Zn-Mediated Decarboxylative Coupling of Chlorostibines to Access Alkylstibines with Stable C(sp3)-Sb Bonds.

Herein, decarboxylative C(sp3)-Sb coupling of aliphatic carboxylic acid derivatives with chlorostibines to access alkylstibines has been achieved. This catalyst-, ligand-, and base-free approach using zinc as a reductant affords various kinds of benzyldiarylstibines and other monoalkyldiarylstibines and tolerates various functional groups, including chlorine, bromine, hydroxyl, amide, sulfone, and cyano groups. The late-stage modification and the gram-scale experiments illustrate its potential application.

Protective effects of the secondary metabolites from Quercus salicina Blume against gentamicin-induced nephrotoxicity in zebrafish (Danio rerio) model.

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

Tuning Dynamic Structural Evolution of Bi24O31Cl10 for Enhancing Piezo-Photocatalytic Nitrogen Oxidation to Nitrate.

Direct nitrogen oxidation into nitrate under ambient conditions presents a promising strategy for harsh and multistep industrial processes. However, the dynamic structural evolution of active sites in surface reactions constitutes a highly intricate endeavor and remains in its nascent stage. Here, we constructed a Bi24O31Cl10 material with moiré superlattice structure (BCMS) for direct piezo-photocatalytic oxidation of nitrogen into nitrate. Excitingly, BCMS achieved excellent nitric acid production (15.44 mg g-1 h-1) under light and pressure conditions. Detailed experimental results show that the unique structure extracts the local strain tensor from the constricting Bi-Bi bond and Bi-O bond for internal structural reconstruction, which promotes the formation of electron and reactive molecule vortexes to facilitate charge transfer as well as N2 and O2 adsorption. Ultimately, these initiatives strengthen electron exchange between the superoxide radical and nitrogen as well as the binding strength of multiple intermediates, which swayingly adjusts the reaction path and energy barriers.

Local weak hydrogen bonds induced dipole-dipole interactions in polymer for enhancing photocatalytic oxidation.

Functionalizing organic polymers is an effective strategy for enhancing their photocatalytic performance. However, this approach is currently limited by specific motifs, complex preparation methods, and an unclear electron transfer mechanism. Here, we present a meticulously designed structure of perylene diimide connected with poly (barbituric acid trimer) through self-assembled hydrogen bonding. In particular, the local chemical environment of the two components is adjusted by hydrogen bond-induced dipole-dipole interactions, leading to the emergence of a significant inherent electric field. Additionally, the formation of hydrogen bonds provides electronic pathways that facilitate charge transfer from perylene to adjacent units. Moreover, the distinctive electronic structure enhances polarity transfer and improves activation and adsorption capabilities for reactive molecules. Ultimately, B-PDI exhibits outstanding oxidation rates for benzylamine to N-benzylidene-benzylamine (10.03 mmol g-1h-1) and selectivity (>99.99 %). Our work offers a widely popular approach for enhancing the photocatalytic activity of organic semiconductor materials by constructing hydrogen bonds in heterogeneous molecules.

Exosomal Tenascin-C primes macrophage pyroptosis amplifying aberrant inflammation during sepsis-induced acute lung injury.

Sepsis-induced acute lung injury (ALI) is a serious complication of sepsis and the predominant cause of death. Exosomes released by lung tissue cells critically influence the progression of ALI during sepsis by modulating the inflammatory microenvironment. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbates ALI in septic infection remain undefined. Our study found increased levels of exosomal Tenascin-C (TNC) in the plasma of both patients and mice with ALI, showing a strong association with disease progression. By integrating exosomal proteomics with transcriptome sequencing and experimental validation, we elucidated that LPS induce unresolved endoplasmic reticulum stress (ERs) in alveolar epithelial cells (AECs), ultimately leading to the release of exosomal TNC through the activation of PERK-eIF2α and the transcription factor CHOP. In the sepsis mouse model with TNC knockout, we noted a marked reduction in macrophage pyroptosis. Our detailed investigations found that exosomal TNC binds to TLR4 on macrophages, resulting in an augmented production of ROS, subsequent mitochondrial damage, activation of the NF-κB signaling pathway, and induction of DNA damage response. These interconnected events culminate in macrophage pyroptosis, thereby amplifying the release of inflammatory cytokines. Our findings demonstrate that exosomal Tenascin-C, released from AECs under unresolved ER stress, exacerbates acute lung injury by intensifying sepsis-associated inflammatory responses. This research provides new insights into the complex cellular interactions underlying sepsis-induced ALI.

Local polarization redistribution in ZnmIn2S3+m for the enhancing synergetic piezo-photocatalytic overall water splitting.

Piezo-photocatalytic water (deuterium oxide) decomposition is a promising strategy for realizing renewable energy, but the manipulation of the polar center remains a big challenge. This study uses a simple low-temperature hydrothermal process to successfully manufacture ZnmIn2Sm+3 (m = 1-3) (ZnIn2S4, Zn2In2S5 and Zn3In2S6). Incorporating both experimental and theoretical analyses, the structural contraction and local polarization of the Zn-S bond in Zn2In2S5 enhance the piezoelectric response and surface charge accumulation, which facilitate charge transfer and reduce the activation energy of water. Remarkably, Zn2In2S5 exhibits excellent piezoelectric photocatalytic total water splitting performance (H2/O2: 4284.72/1967.00 µmol g-1h-1), which is 1.77 times that of photocatalytic performance. Moreover, a significant enhancement in D2O splitting performance can be obtained for the optimized Zn2In2S5. Our work offers valuable insights into the disclosure of local polarization in catalysts for enhancing piezo-photocatalytic overall water splitting.

Analysis of influencing factors and construction of prediction model for postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy: a single-center retrospective cohort study.

BACKGROUND: With the increasing number of bariatric surgeries, the high incidence of postoperative nausea and vomiting (PONV) associated with this surgery has also gradually attracted attention. Among the common bariatric surgery methods, patients undergoing sleeve gastrectomy (SG) have the highest incidence of nausea and vomiting. The mechanism of occurrence of PONV is very complex. This study aims to explore the influencing factors of PONV in patients undergoing laparoscopic sleeve gastrectomy (LSG) and construct a nomogram prediction model based on these factors. METHODS: With the approval of the Ethics Committee, the electronic medical records of patients who underwent LSG from July 2022 to May 2023 were collected retrospectively. RESULTS: A total of 114 patients with complete medical records who underwent LSG from July 2022 to May 2023 were included in this study. Among them, 46 patients developed PONV, resulting in a PONV incidence rate of 40.4%. Multivariate logistic regression analysis revealed that female gender, the use of inhalation anesthesia, and operation time ≥ 120 min were risk factors for PONV in LSG. Additionally, the use of more than two kinds of antiemetic drugs was identified as a protective factor. Based on these factors, a nomogram model was constructed. CONCLUSION: PONV in patients undergoing LSG is related to gender, type of anesthesia, duration of surgery, and combination therapy with antiemetic drugs. The nomogram prediction model constructed in this study demonstrates high accuracy and discrimination in predicting the occurrence of PONV in patients undergoing LSG.

Effect of rmEGF combined with ELF-EMF on promoting wound healing in rats.

BACKGROUND: The process of wound healing is complex, and expediting it remains a challenge. The advantages of extremely low frequency electric and magnetic fields (ELF-EMF) are its non-invasive treatment, promotes healing and promotes myogenesis of C2C12 cells. Epidermal growth factor (EGF) is known to play a vital role in promoting wound healing, so a combination of ELF-EMF and EGF can have far-reaching significance. OBJECTIVE: To study the effect of recombinant murine epidermal growth factor (rmEGF) combined with ELF-EMF on wound healing. METHODS: Thirty-six rats were randomly divided into three groups: normal control group, EGF group, and ELF-EMF+EGF group, and a 20 mm × 20 mm dorsal wound was made. The wound healing rate of rats was calculated on the 3rd, 7th, 11th and 15th day. HE staining was used to observe the micro-morphological changes during the wound healing process. RESULTS: The wound healing rate of EGF+ELF-EMF group was better than other groups. On the 15th day of wound healing, the wounds of each group were completely healed. On the 3rd, 7th, 11th and 15th day of HE staining, the early inflammatory cell infiltration, the arrangement of fibroblasts and the number of new capillaries in the wounds of EGF+ELF-EMF group were better than those of the other groups. CONCLUSIONS: rmEGF combined with ELF-EMF significantly promotes wound healing in SD rats.

A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

Effect of ultrasound-guided lung recruitment to reduce pulmonary atelectasis after non-cardiac surgery under general anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: At present, the application of bedside lung ultrasound is increasing gradually, but there is no relevant expert consensus or guidance for its evaluation in the field of perioperative anesthesia. Through this meta-analysis, we tried to determine the impact of ultrasound-guided lung recruitment maneuvers (LRM) on perioperative patients. METHODS: We searched PubMed, Cochrane Library database, Embase, and Clinical Trials gov for the randomized controlled trials (RCTs) published up to December 31, 2022. The primary outcome was the incidence of postoperative atelectasis. Secondary outcomes included lung ultrasound score (LUS) and LUS of each part. A total of 443 patients were examined in nine randomized controlled trials. RESULTS: The incidence of atelectasis after surgery in patients with ultrasound-guided LRM was less (RR 0.31; 95% CI 0.25-0.40; p < 0.05). The LUS (WMD - 6.24; 95% CI - 6.90-5.59; p < 0.05) and the LUS of each part (LUS in front lung region (WMD - 2.00; 95% CI - 2.49 to - 1.51; p < 0.05); LUS in lateral lung region (WMD - 2.50; 95% CI - 3.20 to - 1.80; p < 0.05); LUS in posterior lung region (WMD - 3.24; 95% CI - 4.23 to - 2.24; p < 0.05)) in patients with ultrasound-guided LRM were lower. CONCLUSION: Ultrasound-guided lung recruitment maneuvers have been shown to be a promising approach for improving perioperative lung ventilation by increasing aeration while mitigating the development of atelectasis. In comparison to non-ultrasound-guided methods, this technique has exhibited superior effects.

Zn-Catalyzed Dehydroxylative Phosphorylation of Allylic Alcohols with P(III)-Nucleophiles.

A novel and efficient protocol for the synthesis of diarylallyl-functionalized phosphonates, phosphinates, and phosphine oxides through the zinc-catalyzed dehydroxylative phosphorylation of allylic alcohols with P(III)-nucleophiles via a Michaelis-Arbuzov-type rearrangement is reported. A broad range of allylic alcohols and P(III)-nucleophiles (P(OR)3, ArP(OR)2, and Ar2P(OR)) are well tolerated in this reaction, and the expected dehydroxylative phosphorylation products could be synthesized with good to excellent yields under the optimal reaction conditions. The reaction can be easily scaled up at a gram-synthesis level. Furthermore, through the step-by-step control experiments, kinetic study experiments, and 31P NMR tracking experiments, we acquired insights into the reaction and proposed the possible mechanism for this transformation.

Trivalent Organostibines: Sb,N Ligands in Double N-Arylation of Primary Amines toward Functionalized Carbazoles.

A Sb,N ligand (L-Sb) for Pd-catalyzed double N-arylation of primary amines was developed. This trivalent ligand L-Sb, containing a 5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine skeleton and stable under air and moisture, could be synthesized facilely on a gram scale from chlorostibine (1) and cyclopentylmagnesium bromide. L-Sb showed excellent catalytic performance in Pd2(dba)3-catalyzed double N-arylation of 2,2'-dibromo-1,1'-biphenyl (2) with primary amines (3), affording functionalized carbazoles in good yields. This Pd2(dba)3/L-Sb-catalyzed double N-arylation, the first example of the application of trivalent organostibines as a ligand in N-arylation, featured the following advantages: small catalyst loading, wide functional group tolerance, good yields, and ease of gram-scale synthesis.

Nickel-Catalyzed C(sp3)-Sb Coupling of Chlorostibines with Unactivated Alkyl Chlorides and In Vitro Anticancer Activity of Products.

In this study, we present a nickel-catalyzed reductive C(sp3)-Sb coupling of unactivated alkyl chlorides with chlorostibines. This approach is highly versatile, tolerating various functional groups such as acetal, alkene, nitrile, amine, ester, silyl ether, thioether, and various heterocyclic compounds. Notably, the late-stage modification of bioactive molecules and the satisfactory anticancer activity against cancerous MDA-MB-231 also demonstrate the potential application.

[Effects of Tomato Planting Years on Soil Physical and Chemical Properties and Microbial Communities].

Long-term continuous cropping of facility soils could influence soil properties; however, the differences in soil properties among different continuous cropping years are still not well understood. The objective of this study was to explore the effects of continuous cropping years of tomato on the physical and chemical properties and biological characteristics of facility soil. Conventional analysis, high-throughput sequencing, and other methods were used to examine the soil physicochemical properties, soil microbial community diversity, and enzyme activities in facility soil after continuous tomato cropping for 1-3 years, 5-7 years, and more than 10 years. As the continuous tomato cropping years increased, soil bulk density and pH decreased; soil maximal water holding capacity increased; and organic matter, total nitrogen, and total phosphorus accumulated. As continuous cropping years increased, the total salt and EC value decreased with continuous cropping for 5-7 years and increased from 5-7 years to more than 10 years continuous cropping and showed a trend of secondary soil salinization. There was a significant increase in alkaline phosphatase for 1-3 years to 5-7 years continuous tomato cropping. There were significant differences in fungal community abundance among different cropping years. The Simpson index and Shannon index of fungi showed a trend of increasing first and then decreasing with the extension of continuous cropping years and reached the maximum value at 5 years of continuous cropping. The Chao1 index decreased continuously following the cropping years. As continuous cropping years increased, Streptomyces became the dominant bacteria, and Aspergillus and Pseudaleuria became the dominant fungi. The key factors affected by continuous cropping years were available potassium and available nitrogen based on the redundancy analysis. The results of this study lay the foundation for future research on the influence of continuous cropping years on the health of facility soil.

[Microbial Diversity and Population Structure of Different Salinized Soil Types in Hebei Province].

The objective of this study was to explore the microbial diversity and community composition under saline soil and to screen the salt-tolerant microbial flora from salinization habitats. The soil from three different habitats(primary salinization, secondary salinization, and healthy soil) in Hebei Province were sampled. The convention method and high-throughput sequencing technology were used to examine the physicochemical properties and microorganism diversity. The soil chemical properties of the three habitats were significantly different. Compared with those of field soil, the soil OM, AP, AK, TS, and EC values of greenhouse soil and TS and EC values of coastal saline soil were significantly higher. However, other chemical indexes of coastal saline soil were significantly lower. The diversity index and abundance of soil bacteria in greenhouse soil were the highest, followed by those in field soil and coastal saline soil as the lowest. The diversity index and abundance of fungi in two saline habitats were significantly lower than that in field soil. The community structure of saline soil was analyzed at the phylum and genus levels. Chloroflexi and its genera and Ascomycota and its genera, such as Trichocladium and Fusarium, were the dominant microbial groups in saline soil. EC and TS were the main factors affecting microbial diversity and community composition. EC and TS were positively correlated with unclassified_A4b, unclassified_Chloroflexi, unclassified_α-Proteobacteria, Trichocladium, unclassified_Chaetomiaceae, Crassicarpon, Cephaliophora, and Sodiomyces. The results of this study lay the foundation for future research on screening microbial resources needed for saline soil remediation.

Ruthenium-Catalyzed 1,6-Hydroalkylation of para-Quinone Methides with Ketones via the in Situ Activation of C(sp3)-H Bonds.

A simple and efficient method for the ruthenium-catalyzed 1,6-hydroalkylation of para-quinone methides (p-QMs) with ketones via the in situ activation of C(sp3)-H bonds has been disclosed. Without the need for preactivation of the substrates and oxidant, a broad range of p-QMs and ketones are well tolerated, producing the expected 1,6-hydroalkylation products with moderate to good yields. Step-by-step control experiments and DFT calculation were conducted systematically to gain insights for the plausible reaction mechanism. This finding may have potential application in the selective diarylmethylation of ketones at the α-C position in organic synthesis.

Is acupoint injection the optimal way to administer mecobalamin for diabetic peripheral neuropathy? A meta-analysis and trial sequential analysis.

Objective: Mecobalamin is a commonly used drug in the treatment of diabetic peripheral neuropathy (DPN). This study aimed to systematically evaluate the efficacy and safety of acupoint injection of mecobalamin for DPN. Methods: Relevant clinical trials on acupoint injection of mecobalamin for DPN published before 31 January 2023 were searched in eight commonly used databases. After screening and confirming the included studies, meta-analysis and trial sequential analysis were performed. Results: A total of 10 relevant studies were confirmed, and the total sample size was 927 cases. On the efficacy endpoints, meta-analysis showed that compared with other administration methods, acupoint injection of mecobalamin significantly increased the clinical effective rate by 27% [RR = 1.27, 95% CI = (1.19, 1.36), P < 0.00001], motor nerve conduction velocity (median nerve) by 5.93 m/s [MD = 5.93, 95% CI = (4.79, 7.07), P < 0.00001], motor nerve conduction velocity (common peroneal nerve) by 5.66 m/s [MD = 5.66, 95% CI = (2.89, 8.43), P < 0.0001], sensory nerve conduction velocity (median nerve) by 4.83 m/s [MD = 4.83, 95% CI = (3.75, 5.90), P < 0.00001], and sensory nerve conduction velocity (common peroneal nerve) by 3.60 m/s [MD = 3.60, 95% CI = (2.49, 4.71), P < 0.00001], and trial sequential analysis showed these benefits were conclusive. In terms of safety endpoints, meta-analysis indicated that the total adverse events for acupoint injection were comparable to other methods of administration, and trial sequential analysis suggested that the results needed to be validated by more studies. Subgroup analysis demonstrated that the benefits of acupoint injections of mecobalamin were not limited by the dose, duration of treatment, or number of acupoints reported in the included studies. Harbord's test showed no significant publication bias (P = 0.106). Conclusion: The efficacy of acupoint injection of mecobalamin for DPN was significantly better than other administrations, and its safety was comparable to other administrations. Therefore, acupoint injection may be the optimal method of mecobalamin for DPN. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=454120, identifier: CRD42023454120.

Gastrointestinal adverse events of tirzepatide in the treatment of type 2 diabetes mellitus: A meta-analysis and trials sequential analysis.

BACKGROUND: Tirzepatide (TZP) is a novel drug for type 2 diabetes mellitus (T2DM), but the gastrointestinal (GI) adverse events (AEs) is a limiting factor in clinical application. Therefore, this study systematically evaluated the GI AEs of TZP for T2DM. METHODS: Clinical trials of TZP for T2DM were retrieved from eight databases published only from the establishment of the database to February 2023. Revman5.3 and TSA0.9.5.10 Beta were used for meta-analysis and trials sequential analysis (TSA). RESULTS: Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05). TSA showed that the differences in total GI AEs, nausea, decreased appetite and constipation were conclusive. Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05), and dyspepsia was significantly increased with TZP 15 mg (P < .05). TSA showed that these differences were all conclusive. Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg, total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05), while nausea, vomiting, dyspepsia and constipation were significantly different in all dose groups, abdominal pain were not significantly different (P < .05) and TSA showed no conclusive results in this group. CONCLUSION: The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA. Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose. GI AEs of TZP decrease gradually over time, so long-term steady medication may be expected to reduce GI AEs.

A real-world study of recombinant human endostatin combined with PD-1/PD-L1 blockade and chemotherapy for patients with advanced non-small cell lung cancer negative for actionable molecular biomarkers.

The ongoing ENPOWER study exploring the efficacy and safety of the recombinant human endostatin (endostar) combined with programmed cell death 1 antibody sintilimab and chemotherapy showed encouraging efficacy and safety in advanced non-squamous non-small cell lung cancer. To evaluate the real-world efficacy and safety of endostar combined with immune checkpoint inhibitor and chemotherapy (EIC) for advanced non-squamous non-small cell lung cancer patients negative for actionable molecular biomarkers (NSCLCnm), patients with advanced NSCLCnm hospitalized to Zhejiang Provincial People's Hospital from January 2020 to December 2022 were screened for eligibility. The included patients were analyzed for the objective response rate (ORR) and disease control rate (DCR). The pre- and posttreatment expression levels of serum tumor associated biomarkers, chemokines and subpopulations of immune cells in peripheral blood were compared. For the 31 patients with advanced NSCLCnm treated with EIC, the median follow-up and treatment cycles were 18.0 months and 4, respectively. The ORR and DCR were 38.7% and 90.3%, respectively. For those who received EIC as first-line treatment, the ORR and DCR were 63.2% and 94.7%, respectively. EIC significantly decreased expression levels of carcinoma antigen 125, carcinoma embryonic antigen and cytokeratin 19 (P<0.05) in patients who were partial remission or stable disease. Among the 31 patients, 27 (87.1%) experienced at least 1 treatment-related adverse events, and 13 (41.9%) had the treatment-related adverse events of grade 3 or higher. No antiangiogenesis-related adverse events were observed. The current study showed that EIC was potentially effective for patients with NSCLCnm, especially when used as first-line therapy, and well tolerated.