To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective:To review the clinical status based on the best evidence of drug administration in patients with dysphagia, systematically analyze the obstacle factors and promoting factors in the process of evidence transformation, and formulate reform strategies.Methods:Based on the evidence-based nursing research method and the guidance of the Ottawa Model of Research Use (OMRU), the review indicators were developed based on the best evidence. The current status of clinical practice behaviors of 223 patients and 75 nurses in the Neurology, Neurosurgery and Geriatric departments of the Affiliated Hospital of Jiangsu University were reviewed from July to December 2021.Based on the results of the review, qualitative interviews were conducted with 32 potential adopters, and content analysis was used to assess the barriers and contributing factors to the clinical translation of evidence in three aspects: evidence-based change, potential adopters and practice environment, so as to develop effective strategies.Results:Based on the 22 best evidence selected, the evidence-based team developed 25 review indicators to carry out clinical review, showing that the compliance rate of 16 indicators were less than 60%. By analyzing and summarizing the interview results of potential adopters, the main obstacles leading to the low compliance rate of nurses were analyzed as follows: evidence-based reform changed the traditional work mode, and the application of evidence was not convenient; at the level of potential adopters, nurses had poor knowledge and practice, heavy work burden, and low awareness of patients and caregivers; at the level of practice environment, there was lack of nursing norms and procedures for clinical transformation of evidence, and the channels of multi-disciplinary collaboration and communication were not smooth. The main promoting factors were the perfect supervision mechanism of evidence-based nursing projects, the evidence-based group had rich experience in evidence transformation, the management was willing to change, and the practitioners were good at innovation.Conclusions:There is still a large gap between the clinical practice and the best evidence of drug administration in patients with dysphagia. The promoting factors should be fully utilized to overcome the obstacles and implement improvements to promote the effective transformation of evidence into clinical practice.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To investigate the protective effect of human umbilical cord mesenchymal stem cell conditioned medium (HucMSC-cm) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and relevant mechanism of action.Methods:Forty 6-week-old male C57BL/6 mice were selected and randomized (random number) into the sham group, LPS group, LPS + HucMSC-cm (LPS+cm) group, and LPS+HucMSC-cm+Compound C (LPS+cm+cc) group, with 10 mice in each group. Mice were intratracheally injected with LPS (5 mg/kg) to establish ALI model, and intratracheally injected with hucMSC-CM (50 μL) 4 h after LPS treatment. Mice in the LPS+cm+cc group were intraperitoneally treated with Compound C (15 mg/kg) prior to LPS treatment. Neutrophils in peripheral blood were counted with the automated hematology analyzer 72 h after LPS administration. After that, mice were sacrificed, and the lung tissue pathology was observed using hematoxylin eosin (HE) staining. Besides, the expressions of IL-6, ICAM-1, VCAM-1 and P-AMP-activated protein kinase (P-AMPK) in the lung tissues were analyzed by Western blot and immunohistochemical assay. In vitro, human lung microvascular endothelial cells (HuLEC-5a) were cultured and divided into three groups: control group, LPS group (10 μg/ mL), and LPS + HucMSC-cm group. After 24 h of treatment, the expressions of p-AMPK and AMPK were detected by Western blot, and the expressions of IL-6 and IL-8 were detected by real-time fluorescence quantitative PCR. Oneway analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between two groups were performed using the Tukey’s multiple comparison test. Results:Compared with the sham group, the LPS group showed lungs with congestion and swelling, thickened pulmonary septum, and inflammatory cell infiltration. Moreover, in the LPS group, the protein expressions of IL-6 ( P=0.003), ICAM-1 ( P<0.001) and VCAM-1 ( P=0.001) were increased significantly, while the expression of p-AMPK was decreased ( P=0.013), accompanied by an increase in the proportion of neutrophils in peripheral blood ( P<0.001). Compared with the LPS group, the LPS+HucMSC-cm group demonstrated eased congestion, edema and pathological injury of lung tissue, reversed protein expressions of IL-6 ( P=0.003), ICAM-1 ( P=0.002), VCAM-1 ( P=0.006) and P-AMPK ( P=0.002), as well as decreased proportion of neutrophils in peripheral blood ( P<0.005). Compared with the LPS+HucMSC-cm group, the LPS+cm+cc group exhibited more severe lung histopathological injury, significantly increased protein expressions of IL-6, ICAM-1 and VCAM-1 in lung tissues, as well as decreased expression of P-AMPK protein. The results of immunohistochemistry were consistent with those of protein. In vitro experiment, after LPS treatment, the mRNA expressions of IL-6 ( P<0.001) and IL-8 ( P=0.027) were increased and p-AMPK protein expression ( P=0.005) was decreased as compared with the control group. In comparison with the LPS group, the LPS+HucMSC-cm group showed decreased mRNA expression levels of IL-6 ( P=0.003) and IL-8 ( P=0.002), but increased protein level of p-AMPK ( P=0.003). Conclusions:HucMSC-cm has a protective effect against LPS-induced acute lung injury, which is mainly attributed to the inhibited expression of adhesion molecules and inflammatory factors under the activation of AMPK.

Objective: To analyze the epidemiological characteristics of acute paraquat(PQ)poisoning in children in southwest Shandong, and the risk factors for pulmonary interstitial fibrosis. Methods: This retrospective study was performed on the clinical data of children with acute PQ poisoning admitted from January 2013 to December 2017 in 12 hospitals in southwest Shandong.All participants were divided into pulmonary interstitial fibrosis group and no pulmonary interstitial fibrosis group on the basis of the chest CT 14 days after poisoning.The epidemiological characteristics and risk factors of pulmonary interstitial fibrosis were analyzed. Results: During the study period, a total of 307 children with acute PQ poisoning were admitted to 12 hospitals, of which 61 (19.87%) were suffering from acute PQ poisoning.Forty-nine cases with complete clinical data were analyzed, including 26 male and 23 female patients poisoned by oral.The age distribution ranged from 8 months to 14 years.Poisoning mainly occured from July to September of each year.The mortality of acute PQ poisoning was 8.2%(4/49), and the incidence of pulmonary interstitial fibrosis in survival patients was 44.4%(20/45). Statistical differences (P<0.05) were found between the pulmonary interstitial fibrosis and no pulmonary interstitial fibrosis, with regard to the times of blood purification, the time from poison exposure to blood purification, the application rate of glucocorticoids, the concentration of PQ in urine, the pediatric critical illness score, the time from poison exposure to gastric lavage, the white blood count at admission, serum creatinine, arterial blood lactate, PaO₂, PaCO₂, and PaO₂/FiO₂; however, there was no significant difference in the proportion of blood purification treatment, the mode of blood purification treatment, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatine kinase and troponin.Stepwise logistic regression analysis showed that the time from exposure to poison to gastric lavage(OR=0.683, 95%CI 0.210-2.222)and to blood purification(OR=0.0133, 95%CI 0.004-0.042), the times of blood purification(OR=2.862, 95%CI 1.450-5.648), concentration of PQ in urine(OR=1.435, 95%CI 1.085-1.898), and the use of glucocorticoids(OR=0.190, 95%CI 0.048-0.757) were the risk factors for pulmonary interstitial fibrosis(P<0.05). Conclusion Early gastric lavage and blood purification, increasing the frequence of adminitrating purification appropriately, using low-dose glucocorticoids can reduce the incidence of pulmonary interstitial fibrosis of children with acute PQ poisoning.

Objective:To understand the status of sedation and analgesia treatment and management in pediatric intensive care unit(PICU) in Shandong Province, and to provide the basis for the improvement of sedation and analgesia treatment plan.Methods:This study was a multi-center retrospective study.The PICUs of 6 tertiary hospitals in Shandong Province participated in this study.The data of 1 340 children admitted to these 6 PICUs from January 2016 to December 2018 were collected.The age, gender, the pediatric risk of mortality score Ⅲ at 24 hours after admission, whether they received mechanical ventilation, whether they received sedation and(or) analgesia, whether they were monitored sedation and(or) analgesia, and in-hospital mortality were analyzed.The children were divided into the simple sedation group( n=798), the sedation + analgesia group( n=120) and the non-sedation analgesia group( n=422) according to whether they received sedation and(or) analgesia.The diseases, proportion of mechanical ventilation, incidence of hypotension, average length of stay in PICU and in-hospital mortality were compared among the three groups. Results:The median age of the 1 340 children was (13.3±6.4) months, including 786 males(58.7%). Sedation therapy had been carried out in 6 PICUs, of which 5 PICUs had routine sedation assessment; 4 PICUs had carried out analgesic therapy, of which only 2 had routine pain assessment.A total of 918 children(68.5%)received sedation and(or) analgesia, midazolam was the most commonly used sedative drug, followed by dexmedetomidine, and 526 children(57.3%)were monitored for sedation assessment, the most commonly used assessment method was the Richmond agitation sedation score.One hundred and twenty(9.0%)cases received sedation combined with analgesia, fentanyl was the most commonly used analgesic, and 38 children(31.7%) underwent routine pain assessment.There was no significant difference in age and sex among the three groups.The proportion of surgical diseases and patients received mechanical ventilation(100.0%, 120/120) were the highest in the sedation + analgesia group.The proportion of mechanically ventilated patients was the lowest in the non-sedation analgesia group(11.4%, 48/422). The mean duration of mechanical ventilation in the sedation + analgesia group was slightly shorter than that in the simple sedation group( P>0.05). The incidence of hypotension was highest in the sedation + analgesia group, and lowest in the non-sedation analgesia group[21.7%(26/120) vs.2.1%(9/422), P<0.01]. There was no significant difference in in-hospital mortality and mean PICU stay among three groups. Conclusion:Benzodiazepines are still the main sedative drugs used in PICUs in Shandong Province.In recent years, the usage of dexmedetomidine has gradually increased, but the proportion of analgesic use is very low.At present, analgesic and sedative therapy is mainly used for children after surgery and receiving mechanical ventilation.Although analgesic and sedative therapy does not increase the in-hospital mortality and average length of stay in PICU, it increases the incidence of hypotension.The sedative and analgesic treatment and assessment in the PICU of Shandong Province are still not standardized, mainly reflected in infrequently analgesic treatment and the assessment of sedation and pain, which need to be further improved.