Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Liver receptor homolog-1: structures, related diseases, and drug discovery.

Liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is a ligand-regulated transcription factor that plays crucial roles in metabolism, development, and immunity. Despite being classified as an 'orphan' receptor due to the ongoing debate surrounding its endogenous ligands, recent researches have demonstrated that LRH-1 can be modulated by various synthetic ligands. This highlights the potential of LRH-1 as an attractive drug target for the treatment of inflammation, metabolic disorders, and cancer. In this review, we provide an overview of the structural basis, functional activities, associated diseases, and advancements in therapeutic ligand research targeting LRH-1.

Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y85.

Five new diisoprenyl cyclohexene-type meroterpenoids, aspergienynes J-N (1-5), along with three known analogues (6-8), were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85. The chemical structures, including their absolute configurations, were established via spectroscopic data and comparison of experimental and calculated ECD spectra. Cytotoxicity assay results indicated that compound 8 had strong cytotoxicity against HeLa cancer cells, and its IC50 value was 11.8 µM. In addition, flow cytometry analysis revealed that the cytotoxicity of 8 was due to the induction of G1 cell cycle arrest and apoptosis in HeLa cells.

The antinociceptive and anti-alpha-glucosidase effects of glucosides from Hemiphragma heterophyllum Wall.

Hemiphragma heterophyllum Wall. is commonly used in traditional Yi herbal medicine for treating bellyache and toothache. In the current study, an unreported monoterpene glucoside, (S)-thymoquinol O-(6-O-oleuropeoyl)-ß-d-glucopyranoside (1), together with 11 known glucosides were obtained from the whole herb of H. heterophyllum. Their structures were determined based on a detailed analysis of spectroscopic data and acid hydrolysis and methanolysis reactions. Bioassay results showed that compounds 1 and 10 at 40 mg/kg exhibited significant antinociceptive activity in the acetic acid-induced writhing model, with inhibitions of 59.80% and 64.07%, respectively. Moreover, five of the isolates showed moderate anti-α-glucosidase activities with IC50 values ranging from 5.67 to 46.16 µM.

Pleural fluid carbohydrate antigen 72-4 and malignant pleural effusion: a diagnostic test accuracy study.

BACKGROUND: The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE. OBJECTIVE: We aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE. DESIGN: A prospective, preregistered, and double-blind diagnostic test accuracy study. METHODS: We prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA). RESULTS: In all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67. CONCLUSION: Pleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.

Diisoprenyl-cyclohexene-type meroterpenoids from a mangrove endophytic fungus Aspergillus sp. GXNU-Y65 and their anti-nonalcoholic steatohepatitis activity in AML12 cells.

Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds' absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 µM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase.

The safety and effectiveness of a self-made negative pressure suction device in the treatment of chronic wounds.

INTRODUCTION: Chronic wounds are wounds that are not healed or have no healing tendency for more than 1 month due to various factors. In clinical nursing, chronic wounds are often not properly treated, and the treatment efficiency is low. Therefore, it is very important to explore effective methods to deal with chronic wounds. OBJECTIVE: To explore the effect of a self-made negative pressure suction device (NPSD) in the nursing of chronic wounds in the elderly. METHODS: A total of 50 elderly patients with chronic wounds who were hospitalised in our hospital from January 2020 to December 2022 were selected as participants by convenient sampling. According to the random number table method, they were divided into a control group and an observation group, with 25 people in each group. The control group was treated with chloroplast foam dressing, debridement gel and alginate dressing. The observation group was treated with a self-made NPSD on the basis of the control group. The wound healing of the two groups was observed. RESULTS: After the intervention of the self-made NPSD, the granulation tissue coverage rate and wound volume reduction rate of the observation group were significantly increased (p < 0.05), and the positive rate of bacterial infection was significantly decreased (p < 0.05). After 3 months of intervention, the total effective rate of the observation group was significantly higher than that of the control group (χ2  = 3.869, p = 0.0492). CONCLUSION: The self-made NPSD can effectively promote the healing of a chronic wound.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

Diagnostic value of nucleic acid amplification tests for tuberculous pleural effusion.

Diagnosing tuberculous pleural effusion (TPE) is challenging for pulmonologists and laboratory scientists. The gold standards for TPE diagnosis are pleural fluid Ziehl-Neelsen staining, Mycobacterium tuberculosis (Mtb) culture and pleural biopsy. These tools have limitations, including low sensitivity, long turnaround time and invasiveness. The nucleic acid amplification test (NAAT) is a rapid and minimally invasive tool for diagnosing TPE. This review summarizes the diagnostic accuracy of available NAATs for TPE, with a focus on the evidence from systematic reviews and meta-analyses. The NAATs summarized in this review include in-house NAATs, GeneXpert-MTB/RIF, GeneXpert-MTB/RIF Ultra, simultaneous amplification and testing-tuberculosis, FluoroType MTB and loop-mediated isothermal amplification.

Triterpenoid saponins from Psammosilene tunicoides and their antinociceptive activities.

Herein, five undescribed oleanane-type triterpenoid saponins, namely, psammosaponins A-E, along with nine known compounds, were isolated from the roots of Psammosilene tunicoides. Moreover, part of the ethanolic extract of P. tunicoides was acid-hydrolyzed and three aglycones were isolated from the resulting hydrolysate. The structures of all compounds were established through extensive analysis involving 1D and 2D NMR experiments, HRESIMS measurements, chemical derivatization, and comparison of spectroscopic data with the values reported in the literature. In all, 10 of the isolated saponins and the three aglycones were evaluated in the acetic acid-induced writhing model for their antinociceptive activity. At a dose of 40 mg/kg, these compounds exhibited significant inhibitory effects on the mouse writhing response, with inhibitions ranging from 31.9% to 79.3%. In addition, the structure-activity relationships of the isolates were discussed. Among the isolates, quillaic acid 3-O-glucuronide and 16α-hydroxygypsogenic acid showed better antinociceptive activity with inhibitions of 79.3% and 73.7%, respectively. Both isolates also exhibited antinociceptive activities in hot plate and formalin tests on mice. Their antinociceptive mechanism was explored in lipopolysaccharide-stimulated RAW 264.7 cells. These isolates could significantly inhibit the production of nitric oxide and interleukin-6 and downregulate the expression levels of inducible NO synthase, COX-1, and COX-2.

"Cold" colorectal cancer faces a bottleneck in immunotherapy.

The advent of immunotherapy and the development of immune checkpoint inhibitors (ICIs) are changing the way we think about cancer treatment. ICIs have shown clinical benefits in a variety of tumor types, and ICI-based immunotherapy has shown effective clinical outcomes in immunologically "hot" tumors. However, for immunologically "cold" tumors such as colorectal cancer (CRC), only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates. In this review, we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC, and summarize the treatment strategies and challenges of immunotherapy for cold CRC. We also explain the mechanism, biology, and role of immunotherapy for cold CRC, which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.

Diagnostic value of soluble biomarkers for parapneumonic pleural effusion.

Parapneumonic pleural effusion (PPE) is a common complication in patients with pneumonia. Timely and accurate diagnosis of PPE is of great value for its management. Measurement of biomarkers in circulating and pleural fluid have the advantages of easy accessibility, short turn-around time, objectiveness and low cost and thus have utility for PPE diagnosis and stratification. To date, many biomarkers have been reported to be of value for the management of PPE. Here, we review the values of pleural fluid and circulating biomarkers for the diagnosis and stratification PPE. The biomarkers discussed are C-reactive protein, procalcitonin, presepsin, soluble triggering receptor expressed on myeloid cells 1, lipopolysaccharide-binding protein, inflammatory markers, serum amyloid A, soluble urokinase plasminogen activator receptor, matrix metalloproteinases, pentraxin-3 and cell-free DNA. We found that none of the available biomarkers has adequate performance for diagnosing and stratifying PPE. Therefore, further work is needed to identify and validate novel biomarkers, and their combinations, for the management of PPE.

Interpretation of Chinese expert consensus on the pelvic exenteration for primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) / 中华胃肠外科杂志

The China PelvEx Collaborative, under the direction of Colorectal Cancer Committee of the Chinese Medical Doctor Association, Gastrointestinal Surgery Committee of China International Exchange and Promotive Association for Medical and Health, has formulated and issued the Chinese expert consensus for primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) , with the academic support of the Chinese Journal of Gastrointestinal Surgery and Chinese Journal of Colorectal Disease (Electronic Edition). This Consensus refers to the expert consensus developed by the International PelvEx Collaboration, incorporates the latest international multi-center research results and combines the latest research results in China. The Consensus unifies some definitions, clarifies the surgical indications, and puts forward the definition and preventive measures of "empty pelvic syndrome" earlier. For the controversial classification of local recurrent rectal cancer, the Chinese classification was proposed for the first time in Consensus. At the same time, the definition of pelvic exenteration is controversial, and a more consistent cognition is proposed. It is believed that, with the in-depth research on complicated rectal cancer, C-PelvEx will gather more higher-level data from clinical research in several domestic centers, so as to further enrich the content of the updated Consensus.

Laparoscopic versus open pelvic exenteration for locally advanced rectal cancer: analysis of short- and long-term effects / 中华胃肠外科杂志

Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ2=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ2=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ2=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ2=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ2=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.

Pleural fluid soluble Fas ligand and tuberculous pleural effusion: a prospective diagnostic test accuracy study.

Background: The diagnosis of tuberculous pleural effusion (TPE) is challenging for pulmonologists. Adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin-27 (IL-27) have some limitations for diagnosing TPE. Soluble Fas ligand (sFasL) had a high diagnostic value for TPE. However, it remains unknown: (I) whether sFasL has an additional diagnostic value to the traditional markers (e.g., ADA); (II) whether sFasL provides a net benefit in patients with undiagnosed pleural effusion; (III) factors affecting the diagnostic accuracy of sFasL for TPE. This study aimed to evaluate the additional diagnostic value and benefit of pleural fluid sFasL for TPE. Methods: We prospectively enrolled 211 patients with undiagnosed pleural effusion. The concentration of sFasL in pleural fluid was measured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy and net benefit of sFasL and ADA for TPE were analyzed by a receiver operating characteristic (ROC) curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminant improvement (IDI). Results: The area under the ROC curves (AUCs) of sFasL and ADA were 0.74 (95% CI: 0.65-0.83) and 0.80 (95% CI: 0.71-0.90), respectively. The decision curve of sFasL revealed net benefit. The continuous NRI and IDI of sFasL were 0.36 (0.00-0.72, P=0.05) and 0.02 (-0.01-0.06, P=0.18), respectively. Conclusions: Pleural fluid sFasL has moderate diagnostic accuracy for TPE.

The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy for unresectable rectal cancer (SUNRISE): interim analysis of a randomized phase II trial.

PURPOSE: The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis. METHODS AND MATERIALS: Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments. RESULTS: From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group. CONCLUSION: Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.

Epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), a type of Klebsiella pneumoniae (KP) that exhibits hypervirulence and carbapenem resistance phenotypes, can cause severe infections, both hospital- and community-acquired infections. CR-hvKP has brought great challenges to global public health and is associated with significant morbidity and mortality. There are many mechanisms responsible for the evolution of the hypervirulence and carbapenem resistance phenotypes, such as the horizontal transfer of the plasmid carrying the carbapenem resistance gene to hypervirulent Klebsiella pneumoniae (hvKP) or carbapenemase-producing Klebsiella pneumoniae (CRKP) acquiring a hypervirulence plasmid carrying a virulence-encoding gene. Notably, KP can evolve into CR-hvKP by acquiring a hybrid plasmid carrying both the carbapenem resistance and hypervirulence genes. In this review, we summarize the evolutionary mechanisms of resistance and plasmid-borne virulence as well as the prevalence of CR-hvKP.

Two new monoterpene esters from Illigera paviflora Dunn roots.

Two new monoterpene esters, illigerates H and I (1 and 2), and six known compounds actinodaphine (3), bulbocupnine (4), stephanine (5), hypserpanine B (6), betulinic acid (7) and gallic acid (8) were obtained from the root of Illigera paviflora Dunn. Their structures were elucidated by spectroscopic analysis. Anti-inflammatory and α-glucosidase inhibitory activity of some isolated compounds were assessed. Two monoterpenes 1 and 2 exhibited weak in vitro anti-inflammatory activity (IC50 64.5 ± 5.3 and 79.2 ± 7.5 µM) while compounds 3-6 showed inhibition of α-glucosidase with IC50 values ranged from 87.17 to 118.74 µM.