Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: a meta-analysis of phase 3 clinical trials.

Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).

Efficacy of tyrosine kinase inhibitors in patients with advanced or metastatic sarcomas after prior chemotherapy: A meta-analysis.

BACKGROUND: Sarcoma is a heterogeneous malignancy arising from interstitial tissue. Anthracycline-based therapy is the first-line treatment recommended by guidelines for patients with locally advanced or metastatic unresectable sarcoma. Recently, targeted therapies, in particular tyrosine kinase inhibitors (TKIs), have made significant progress in the treatment of sarcoma, and their efficacy has been investigated in randomized controlled trials. The aim of this meta-analysis is to evaluate the efficacy of TKIs in patients with advanced or metastatic sarcoma who have previously received chemotherapy. METHODS: We completed a meta-analysis after conducting literature searches in PubMed, Embase, and Cochrane. The single-drug, placebo-controlled, randomized controlled clinical trials of TKIs in patients with advanced or progressive sarcoma who have previously received chemotherapy are available for inclusion in the study. The observation results were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The subgroup analysis was performed according to histological subtypes of sarcoma. RESULTS: This study included 6 studies, including 1033 patients. The ORR (OR: 7.99, 95% CI: 3.62-19.61, P < .00001), DCR (OR: 2.54, 95% CI: 1.27-5.08, P = .009), PFS (HR: 0.46, 95% CI: 0.34-0.62, P < .00001), and OS (HR: 0.80, 95% CI: 0.67-0.96, P = .02) of patients treated with TKIs were better than those in the placebo group. CONCLUSIONS: In patients with advanced sarcoma, TKIs have been shown to have advantages in terms of ORR, DCR and PFS and OS. Multi-targeted TKIs may be considered as one of the second-line treatment options for sarcoma patients who have received prior chemotherapy.

Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor-Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy.

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm-2). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

Efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in locally advanced esophageal cancer: An updated meta-analysis.

BACKGROUND: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. METHODS: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3 + AEs). RESULTS: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HR = 0.80; 95% CI: 0.68-0.94), PFS (HR = 0.78; 95% CI: 0.66-0.93), pCR (OR = 13.00; 95% CI: 7.82-21.61) and R0 resection (OR = 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (OR = 2.31; 95% CI: 1.26-4.25) and grade 3 + AEs (OR = 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (OR = 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HR = 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HR = 0.80; 95% CI: 0.63-1.08). CONCLUSIONS: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3 + AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.

Rectal metastasis of gastric cancer: a case report.

The most common metastatic sites of gastric cancer include the liver, peritoneum, lung, and bone. However, there is a lack of relevant clinical reports regarding rectal metastasis. Herein, we report the rare case of a patient with gastric cancer who developed rectal metastasis. A 57-year-old male patient was diagnosed with gastric cancer and underwent a radical gastrectomy in January 2016, followed by eight cycles of adjuvant chemotherapy. The patient subsequently developed a rectal mass in March 2021. He was diagnosed with rectal adenocarcinoma and underwent surgical resection of the rectal tumor. A mass was then found in the abdominal wall in September 2021 and was resected. Specimens obtained from the three surgeries were reviewed, and the rectal tumor and the mass in the abdominal wall were both found to be metastatic tumors from the gastric cancer. Metastasis of gastric cancer to the rectum is rare, but it is important to differentiate between rectal metastasis and primary rectal cancer to help avoid unnecessary treatment.

Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials.

Objective: Zolbetuximab is a "first-in-class" chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results: This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68-0.84) and PFS (HR = 0.64; 95% CI: 0.50-0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82-1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55-0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44-0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common. Conclusion: This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).

Pseudoprogression Disease in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy.

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is on the rise annually. It is characterized by low differentiation, high malignancy, and rapid growth. Consequently, treatment options are limited, and the patient's prognosis is poor. The emergence of immunotherapy has partially improved the survival and prognosis of SCLC patients. However, a unique response known as "pseudoprogression" during immunotherapy has raised concerns. The occurrence of tumor enlargement despite a positive response to immune checkpoint inhibitor therapy undoubtedly affects the assessment of clinical drug efficacy and the selection of subsequent treatment strategies. In this article, we analyze a clinical case of pseudoprogression in a patient with SCLC who received immune therapy (Durvalumab). Currently, there is insufficient evidence-based medicine to guide the diagnosis, differentiation and subsequent treatment strategies for pseudoprogression in SCLC following immunotherapy. Through this case report and literature review, we aim to provide diagnostic and therapeutic insights for the clinical use of immunotherapy in advanced SCLC. Additionally, we hope that fellow readers of this article can engage in further collaborative discussions through more clinical research.

Water-soluble fluorescent probes for differentiating cancer cells and normal cells by tracking lysosomal viscosity.

Lysosomal viscosity is a significant parameter of lysosomes and closely related to various diseases. Herein, two fluorescent probes, Lyso-vis-A and Lyso-vis-B, were developed, which demonstrate diverse advantages, including great water solubility, lysosome targeting ability and viscosity sensitivity. In particular, Lyso-vis-A exclusively showed fluorescence response toward viscosity but was not influenced by pH changes, rendering it a selective lysosomal viscosity probe. Furthermore, Lyso-vis-A was successfully applied to monitor lysosomal viscosity variations in living cells and differentiate cancer cells and normal cells.

Ascending colon cecal junction carcinoma with prostate metastasis: A case report and literature review.

RATIONALE: Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are the liver, lungs, peritoneum, and lymph nodes, while the incidence of metastases to the prostate is low. There are few relevant studies on colon carcinoma, most of them being case reports. PATIENT CONCERNS: A 76-year-old man treated with radical resection of right colon carcinoma due to primary poorly differentiated adenocarcinoma of the cecum. Postoperative pathological examination suggested that he had cancer at the junction of the ascending colon and the cecum. He had received adjuvant chemotherapy after surgery. One year later, he received transurethral plasma resection of the prostate due to urinary system discomfort. Postoperative pathological immunohistochemistry suggested prostate metastasis of colorectal carcinoma, and he received individualized treatment, but this produced no clear survival benefit. DIAGNOSES: Ascending colon cecal junction carcinoma with prostate metastasis. INTERVENTIONS: Radical resection, chemotherapy, anti-androgen therapy, surgery to relieve primary lesion obstruction symptoms, and local radiotherapy of the prostate. OUTCOMES: At present, clinical cases of colon carcinoma with prostate metastasis are rare. By sharing a rare case of ascending colon cecal junction carcinoma with prostate metastasis and reviewing the relevant literature, this paper explores and optimizes the clinical treatment of colon carcinoma with prostate metastasis.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Universal Strategy to Develop Fluorogenic Probes for Lysine Deacylase/Demethylase Activity and Application in Discriminating Demethylation States.

Dynamically controlling the post-translational modification of the ε-amino groups of lysine residues is critical for regulating many cellular events. Increasing studies have revealed that many important diseases, including cancer and neurological disorders, are associated with the malfunction of lysine deacylases and demethylases. Developing fluorescent probes that are capable of detecting lysine deacylase and demethylase activity is highly useful for interrogating their roles in epigenetic regulation and diseases. Due to the distinct substrate recognition of these epigenetic eraser enzymes, designing a universal strategy for detecting their activity poses substantial difficulty. Moreover, designing activity-based probes for differentiating their demethylation states is even more challenging and still remains largely unexplored. Herein, we report a universal strategy to construct probes that can detect the enzymatic activity of epigenetic "erasers" through NBD-based long-distance intramolecular reactions. The probes can be easily prepared by installing the O-NBD group at the C-terminal residue of specific peptide substrates by click chemistry. Based on this strategy, detecting the activity of lysine deacetylase, desuccinylase, or demethylase with superior sensitivity and selectivity has been successfully achieved through single-step probe development. Furthermore, the demethylase probe based on this strategy is capable of distinguishing different demethylation states by both absorption and fluorescence lifetime readout. We envision that these newly developed probes will provide powerful tools to facilitate drug discovery in epigenetics in the future.

Decreased frequency of a novel T-lymphocyte subset, CD3+ CD4- CD7+ CD57- T cells, in hepatitis B virus-related end-stage liver disease might contribute to disease progression.

CD7 and CD57 are related to the differentiation and functional stages of CD8+ T cells. However, the role of their combined presence in CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3+ CD4- CD7+ CD57- T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3+ CD4- CD7+ CD57- T cell frequency. Furthermore, the prevalence of CD3+ CD4- CD7+ CD57- T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3+ CD4- CD7+ CD57- T cells in a dose-dependent manner. CD3+ CD4- CD7+ CD57- T cells displayed a B and T lymphocyte attenuator (BTLA)high CD25high CD127high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.

A single-center randomized controlled study of intraperitoneal hyperthermic chemoperfusion in combination of recombinant human tumor necrosis factor (TNF) in treatment of malignant ascites caused by advanced abdominal cancers.

INTRODUCTION: Malignant peritoneal effusion is a common complication of advanced malignancies, which has a poor prognosis for patients. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used in the treatment of advanced gynecological tumors, especially ovarian cancer (OC). Relative studies have indicated that HIPEC allows for direct exposure of tumor cells to high peritoneal concentrations of cytotoxic drugs without increasing systemic toxicity compared with intravenous treatment. Recombinant human tumor necrosis factor for injection (rmhTNF-NC) is a safely tolerated immunotherapeutic drug that has becoming a mainstay of treatment for malignant effusions. Currently, a prospective study is required to determining the efficacy of rmhTNF-NC plus cisplatin for the treatment of malignant peritoneal effusion for OC. METHODS: Design and setting: This is a single-center, open trial will be performed in Zhongshan Affiliated Hospital, Guangzhou University of Chinese Medicine. PARTICIPANTS: Eligible patients will be those with advanced gynecologic cancers and who would be suitable for HIPEC. INTERVENTION AND CONTROL: HIPEC with cisplatin and intraperitoneal perfusion with rmhTNF-NC. COINTERVENTIONS: Further chemotherapy will be offered to patients as per current practice.OutcomesPilot study: Patients and clinicians' acceptability of the trial to assist in optimization of recruitment.Primary outcome: One-year overall survival (OS).Secondary outcomes: Progression-free survival (PFS), adverse events.Follow-up: One-year follow-up for OS.Sample size: Twenty patients to demonstrate therapeutic effect of peritoneal effusion caused by OC. DISCUSSION: This trial will determine the effectiveness of HIPEC with cisplatin and intraperitoneal perfusion with rmhTNF-NC for advanced gynecologic cancers, and guide the optimal treatment for these patients.

Self-assembled nano-photosensitizer for targeted, activatable, and biosafe cancer phototheranostics.

Cancer treatment currently still faces crucial challenges in therapeutic effectiveness, precision, and complexity. Photodynamic therapy (PDT) as a non-invasive tactic has earned widespread popularity for its excellent therapeutic output, flexibility, and restrained toxicity. Nonetheless, drawbacks, including low efficiency, poor cancer specificity, and limited therapeutic depth, remain considerable during the cancer treatment. Although great effort has been made to improve the performance, the overall efficiency and biosafety are still ambiguous and unable to meet urgent clinical needs. Herein, this study integrates merits from previous PDT strategies and develops a cancer-targeting, activatable, biosafe photosensitizer. Owing to excellent self-assembly ability, this photosensitizer can be conveniently prepared as multifunctional nano-photosensitizers, namely MBNPs, and applied to in vivo cancer phototheranostics in "all-in-one" mode. This study successfully verifies the mechanism of MBNPs, then deploys them to cell-based and in vivo cancer PDT. Based on the unique cancer microenvironment, MBNPs achieve precise distribution, accumulation, and activation towards the tumor, releasing methylene blue as a potent photosensitizer for phototherapy. The PDT outcome demonstrates MBNPs' superior cancer specificity, remarkable PDT efficacy, and negligible toxicity. Meanwhile, in vivo NIR fluorescence and photoacoustic imaging have been utilized to guide the PDT treatment synergistically. Additionally, the biosafety of the MBNPs-based PDT treatment is ensured, thus providing potential for future clinical studies.

Systematic Screening of Trigger Moieties for Designing Formaldehyde Fluorescent Probes and Application in Live Cell Imaging.

Formaldehyde (FA) is involved in multiple physiological regulatory processes and plays a crucial role in memory storage. Meanwhile, FA has a notorious reputation as a toxic compound, and it will cause a variety of diseases if its level is unbalanced in the human body. To date, there have been numerous fluorescent probes for FA imaging reported. Among them, the probes based on the 2-aza-Cope rearrangement have attracted the most attention, and their applications in cell imaging have been greatly expanded. Herein, we screened the various trigger moieties of FA fluorescent probes based on the mechanism of 2-aza-Cope rearrangement. FA-2, in which a fluorophore is connected to a 4-nitrobenzylamine group and an allyl group, demonstrated the highest sensitivity, selectivity, and reaction kinetics. Furthermore, FA-Lyso, derived from FA-2, has been successfully designed and applied to monitor exogenous and endogenous FA fluctuations in lysosomes of living cells.

Case report: pathological complete response in an IIIB non-small cell lung cancer patient after preoperative neoadjuvant nivolumab therapy combined with chemotherapy.

RATIONALE: For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer. PATIENT CONCERNS: A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to "coughing for more than one month.". The patient had nothing of note in either his medical history or that of his family, and no history of smoking. DIAGNOSIS: The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery. INTERVENTIONS: The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21. OUTCOMES: The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR). LESSONS: In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.

Photoacoustic/Fluorescence Dual-Modality Probe for Biothiol Discrimination and Tumor Diagnosis in Cells and Mice.

Developing probes to simultaneously detect and discriminate biothiols is important, yet challenging. Activatable photoacoustic (PA) probes for discriminating biothiols in vivo are still lacking, and this hinders the diagnosis of thiol-related diseases. Herein we present the first PA and fluorescence dual-modality probe MB-NBD for discriminating different biothiol species. The probe has the advantages of both fluorescence imaging and PA imaging (high sensitivity and deep penetration) with distinct signal patterns toward hydrogen sulfide (H2S), cysteine/homocysteine (Cys/Hcy), and glutathione (GSH) treatment. The biothiol-activated product of MB-NBD exhibits enhancements in near-infrared fluorescence (NIRF) at 690 nm and absorbance/PA at 664 nm upon fast reaction, allowing it to selectively detect biothiol species over other reactive species. On the other hand, MB-NBD displays characteristic absorbance enhancement at 547 nm toward H2S, rendering specific detection of H2S. In addition, the specific enhancements in absorbance/PA at 470 nm and fluorescence at 550 nm toward Cys/Hcy treatment endows the probe with the capability of selectively detecting Cys/Hcy. Furthermore, MB-NBD is able to discriminate Cys and GSH by fluorescent imaging in live-cell and ratiometric PA imaging in mice experiments. MB-NBD has been successfully used to diagnose tumors by dual-channel ratiometric PA imaging.

Reaction-based fluorescent and chemiluminescent probes for formaldehyde detection and imaging.

Formaldehyde (FA), a reactive carbonyl species, is classified as Group 1 carcinogen by International Agency for Research on Cancer (IARC) in 2004. In addition, clinical studies have implicated that elevated levels of FA have been associated with different kinds of diseases, such as neurodegenerative diseases, diabetes, and chronic liver and heart disorders. However, in addition to the direct inhalation of FA in the environment, most organisms can also produce FA endogenously by demethylases and oxidases during the metabolism of amino acids and xenobiotics. Since FA plays an important role in physiological and pathological processes, developing reliable and efficient methods to monitor FA levels in biological samples is crucial. Reaction-based fluorescent/chemiluminescent probes have provided robust methods for FA detection and real-time visualization in living organisms. In this highlight, we will summarize the major developments in the structure design and applications of FA probes in recent years. Three main strategies for designing FA probes have been discussed and grouped by different reaction mechanisms. In addition, some miscellaneous reaction mechanisms have also been discussed. We also highlight novel applications of these probes in biological systems, which offer powerful tools to discover the diverse functions of FA in physiology and pathology processes.

Efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis of randomized controlled trials.

Background: The addition of endocrine therapy to salvage radiotherapy (SRT) is expected to further improve the prognosis of patients with biochemical recurrence of prostate cancer after radical prostatectomy (RP). The quantitative synthesis of clinical outcomes of SRT combined with endocrine therapy is limited. Whether salvage radiotherapy plus endocrine therapy remains inconclusive. We performed a systematic review and meta-analysis of existing randomized controlled trials to evaluate the efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy. Methods: A systematic search of PubMed, EMBASE, and the Cochrane library was performed for articles published between January 1, 2012 and October 10, 2022. Data were analyzed using Review Manager 5.4.1 (Cochrane Collaboration Software). Main outcome and measures included biochemical progression-free survival (bPFS), metastasis free survival (MFS), overall survival (OS), and Grade 3 or higher adverse events (3+AEs), including acute and late adverse events. Results: In this systematic review and meta-analysis, 4 randomized controlled studies enrolling 2731 male (1374 of whom received SRT combined with endocrine therapy and 1357 controls) met the inclusion criteria. SRT combined with endocrine therapy were related to significantly improve bPFS (HR=0.52; 95% CI: 0.46 0.59; p<0.00001) and MFS (HR=0.75; 95% CI: 0.64 0.88; p<0.001). Compared with SRT alone, the combination therapy tended to be associated with prolong OS (HR=0.83; 95% CI: 0.69-1.01; p=0.06), but not statistically significant. At early follow-up, the risk of acute AEs was comparable in the two groups (RR=1.04; 95% CI: 0.22-4.85). However, the risk of late AEs was higher in the combination group at later follow-up (RR=1.33; 95% CI: 1.09-1.62). Conclusions: This systematic review and meta-analysis found superior efficacy associated with adding endocrine therapy to SRT compared with SRT alone in patients with biochemical recurrence after RP. Additional endocrine therapy is safe and feasible for patients with biochemical recurrence after RP. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022365432).

The negative impact of increasing age and underlying cirrhosis on the sensitivity of adenosine deaminase in the diagnosis of tuberculous peritonitis: a cross-sectional study in eastern China.

BACKGROUND: Our study aimed to evaluate the correlation between the sensitivity of adenosine deaminase (ADA) testing for the diagnosis of tuberculous peritonitis (TBP) and patient age or cirrhosis status. METHODS: Clinical data for patients clinically diagnosed with TPB (n = 132) or not (n = 147) were assessed. ADA activity was compared among three age groups (< 45 yr, 45-60 yr, and ≥ 60 yr) and among cirrhosis-related subgroups. Cut-off values for the ADA test were analyzed among three patient populations (young non-cirrhotic, n = 97; older non-cirrhotic, n = 115; cirrhotic, n = 67), and validated in a cohort of 259 participants. RESULTS: According to the multivariate regression analyses, age < 45 yr is highly predictive of TBP risk. The young non-cirrhotic TBP patients had higher ADA activity than the middle-aged or old controls (p < 0.01). Significantly decreased activity and efficacy of ADA were observed in the cirrhotic subgroup/population, regardless of age or cohort. For the above-mentioned two non-cirrhotic populations in the validation cohort, the ADA test showed excellent performance using thresholds of 30.5 IU/L and 20.5 IU/L, with respective sensitivities of 91.1% and 92.6%. CONCLUSIONS: ADA activity is negatively associated with increasing age and underlying cirrhosis. Optimizing cut-off values for the ADA test can increase its sensitivity in non-cirrhotic individuals older than 45 years.