[Research progress of CAR-macrophages in malignant hematological diseases].

This article reviews the development history of chimeric antigen receptor macrophage (CAR-M) therapy, discusses its application in malignant hematologic diseases, introduces related clinical trials, analyzes the advantages and challenges faced by CAR-M therapy in clinical application, and looks forward to its future use in the treatment of malignant hematologic diseases.

[Adaptive servo-ventilation in patients with heart failure and sleep apnea: Insights from the ADVENT-HF trial].

Heart failure is strongly associated with obstructive and central sleep apnea. The landmark 2015 SERVE-HF trial showed that using adaptive servo-ventilation (ASV) for central sleep apnea (CSA) management was associated with an increased risk of all-cause and cardiovascular mortality among heart failure patients with reduced ejection fractions. Based on the result, the American Academy of Sleep Medicine and the European Society of Cardiology have recommended against the use of ASV for the treatment of CSA in patients with heart failure with an ejection fraction≤45%. Recently, the results from the ADVENT-HF trial have been formally published, indicating that ASV does not increase adverse outcomes and can improve patients' quality of life. Here, we go over these findings in detail.

[Perceptions of transanal total mesorectal excision surgical quality and patient screening].

As a rapid developing rectal cancer procedure that has been in existence for more than a decade, transanal total mesorectal excision (taTME) has had a rough experience along the way, suggesting the importance of improving its surgical quality. In the current view of quality control of taTME, its main advantages are that it could increase the distance of distal margins, reduce the positive rate of circumferential margins, and improve the quality of total mesorectal excision. As few high-quality clinical studies have been conducted, the limitations brought about by confounding bias and publication bias that could not be excluded in current published studies call for a cautious interpretation of the current conclusions. At this stage taTME is only recommended in highly selective patients and centers. Under these circumstances, we aim to discuss the quality assessment of the taTME procedure and the selection of patients and centers. Based on current evidence and practical experience, we typically select patients with difficult pelvis, low rectal cancer, and/or those requiring direct visual recognition of the distal margin after neoadjuvant chemoradiation to perform taTME in our center.

[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study].

Objective: To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. Methods: This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ2 test or Mann-Whitney U test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results: The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m2 vs. 23.2 [21.3, 25.5] kg/m2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (P=0.668) or overall survival (OS) (P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, P=0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (P=0.343) or OS (P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (P=0.047) and OS (P=0.040) than did patients with pMMR. Conclusions: Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

Microsatellite instability in colorectal cancer.

BACKGROUND: To investigate relationships between microsatellite instability (MSI) and the clinicopathological characteristics of colorectal cancer (CRC) to facilitate the provision of targeted therapy and immunotherapy for CRC related to MSI, and provide a basis for better prognoses. MATERIALS AND METHODS: Data were obtained from the information system of the Pathology Department of the Fourth Affiliated Hospital of Harbin Medical University, China, from January 01, 2021 to September 30, 2022. Clinicopathological information, including sex, age, tumor size, and associated expression of MSI, was collected. RESULTS: CRC associated with MSI usually occurred in people aged over 50 years. It was related to tumor diameter, which was 5-10 cm at the most. Most tumors occurred in the right colon and were moderately to poorly differentiated. PCR detected 29 patients, including 24 cases of microsatellite stable (MSS), one case of MSI-low, and four cases of MSI-high. The expression of mismatch repair (MMR) protein in these 29 patients was also investigated via immunohistochemistry (IHC), which detected 25 cases of MSS and four cases of MSI-high. The consistency between IHC and PCR was 96.6%. CONCLUSION: The expression of MMR is related to age, tumor diameter, tumor location, and tumor differentiation. It was not related to gender, lymphovascular and perineural invasion, lymph node metastasis, TNM stage, or P53 expression. The consistency between IHC and PCR was 96.6%.

[Pseudocarcinomatous hyperplasia of the fallopian tube: a clinicopathological analysis of sixteen cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pseudocarcinomatous hyperplasia of the fallopian tubes. Methods: Sixteen cases of pseudocarcinomatous hyperplasia of the fallopian tubes diagnosed at Obstetrics and Gynecology Hospital of Fudan University from January 2011 to January 2024 were collected.The pathological sections were reviewed, the clinical and pathological data were consulted, and immunohistochemical examination was conducted along with follow-up. Results: The patients were aged from 19 to 57 years, with an average age of 41 and a median age of 38. Among the 16 cases, 4 were located in the right fallopian tubes, 6 in the left fallopian tubes, while the remaining cases presented bilaterally. The general manifestations were tubal edema, crispness and purulent secretion in the lumen. Morphologically, the fallopian tube mucosa exhibited a significant infiltration of neutrophils, lymphocytes and plasma cells. The epithelial cells of the fallopian tube displayed evident proliferation, stratification and disorganized arrangement leading to formation of small glandular cavity with back-to-back, fissure-like and sieve-like structures. Immunohistochemical analysis revealed positivity for CK7 and WT1, along with wild-type p53 expression, Ki-67 index ranged from 5% to 20%. During the follow-up period ranging from 1 to 156 months, all the patients remained free of disease. Conclusions: Pseudocarcinomatous hyperplasia of the fallopian tube is a rare non-neoplastic lesion, which can lead to epithelial hyperplasia and atypical hyperplasia. The most important significance of recognizing this lesion lies in avoiding misdiagnosis of fallopian tube cancer during intraoperative and postoperative pathological examination. This ensures that clinicians can administer correct clinical interventions.

Circulating GDF-15: a biomarker for metabolic dysregulation and aging in people living with HIV.

Despite effective control of HIV replication by antiretroviral therapy (ART), a significant number of people living with HIV (PLWH) fail to achieve complete immune reconstitution and thus are deemed immune non-responders (INRs). Compared with immune responders (IRs) who have restored their CD4 T cell numbers and functions, CD4 T cells from these INRs exhibit prominent mitochondrial dysfunction and premature aging, which play a major role in increasing the incidence of non-AIDS, non-communicable diseases (NCDs). To date, there are no reliable biomarkers that can be used to typify and manage PLWH, especially INRs with non-AIDS NCDs. Growth differential factor-15 (GDF-15) is a transforming growth factor-ß (TGF-ß) family member known to regulate several biological processes involved in cell aging and stress responses. Since PLWH exhibit premature aging and metabolic dysregulation, here we measured the plasma levels of GDF-15 by ELISA and metabolic proteins by proteomic array and correlated the results with clinical parameters in ART-controlled PLWH (including INRs and IRs) and healthy subjects (HS). We found that GDF-15 levels were significantly elevated in PLWH compared to HS. GDF-15 levels were positively correlated with age and negatively associated with body mass and LDL cholesterol levels in the study subjects. Also, elevated GDF-15 levels were correlated with differential dysregulation of multiple metabolic proteins in PLWH. These results suggest that GDF-15 protein may serve as a biomarker of metabolic dysregulation and aging, and this biomarker will be useful in clinical trials targeting aging and metabolic disorders in ART-treated PLWH.

Identification of potential candidate genes for the Huoyan trait in developing Wulong goose embryos by transcriptomic analysis.

1. The Wulong goose is a Chinese breed and a source of high-quality meat and eggs. A characteristic of the Wulong goose is that a proportion of the birds do not have eyelids, known as the Huoyon trait.2. Wulong geese exhibiting the Huoyan trait at embryonic stages of 9 days (E9), 12 days (E12) and 14 days (E14) were selected alongside those with normal eyelids for comprehensive transcriptome sequencing. Differentially expressed gene (DEG) and functional enrichment analyses were performed and finally, eight DEG were chosen to verify the accuracy of qPCR sequencing.3. Overall, 466, 962 and 550 DEG were obtained from the three control groups, D9 vs. N9, D12 vs. N12 and D14 vs. N14, respectively, by differential analysis (p < 0.05). CDKN1C, CRH, CROCC and TYSND1 were significantly expressed in the three groups. Enrichment analysis revealed the enrichment of CROCC and TYSND1 in pathways of cell cycle process, endocytosis, microtubule-based process, microtubule organising centre organisation, protein processing and protein maturation. CDKN1C and CRH were enriched in the cell cycle and cAMP signalling pathway.4. Some collagen family genes were detected among the DEGs, including COL3A1, COL4A5, COL4A2 and COL4A1. FREM1 and FREM2 genes were detected in both Huoyan and normal eyelids. There was a significant difference (p < 0.01) in FREM1 expression between ED9 and ED14 in female embryos, but this difference was not observed in male embryos.

[Value of peripheral blood rare cell EGFR gene amplification detection in the evaluation of benign and malignant pulmonary nodules].

Objective: To explore the value of detection of epidermal growth factor receptor (EGFR) gene amplification in peripheral blood rare cells in the assessment of benign and malignant pulmonary nodules. Methods: A total of 262 patients with pulmonary nodules were selected as the retrospectively study subjects from the Second Affiliated Hospital of Army Military Medical University and Peking Union Medical College Hospital from July 2022 to August 2023. There were 98 males and 164 females, with the age range from 16 to 79 (52.1±12.1) years. The EGFR gene amplification testing was performed on the rare cells enriched from patients' peripheral blood, and the clinical manifestations, CT imaging features, histopathological and/or pathological cytological confirmed results of patients were collected. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of the method of detection of EGFR gene amplification in peripheral blood rare cells, and its diagnostic efficacy was evaluated. Results: Among the 262 patients, 143 were malignant pulmonary nodules and 119 were benign pulmonary nodules. The differences between malignant pulmonary nodules and benign pulmonary nodules in nodule diameter and nodule density were statistically significant (both P<0.001), while the differences in age, gender and nodule number were not statistically significant (all P>0.05). The number [M (Q1, Q3)] of EGFR gene amplification positive rare cells in patients with malignant pulmonary nodule was 8 (6, 11), which was higher than that in patients with benign pulmonary nodule [2 (1, 4), P<0.001]. The ROC curve results showed that when the optimal cut-off value was 5 (that was, the number of EGFR gene amplification positive rare cells was>5), the area under the curve (AUC) of the detection of EGFR gene amplification in peripheral blood rare cells for discrimination of benign and malignant pulmonary lesions was 0.816 (95%CI: 0.761-0.870), with a sensitivity of 83.2%, a specificity of 80.7%, and an accuracy of 82.1%. Based on the analysis of the diameter of the nodules, the AUC for distinguishing between benign and malignant pulmonary nodules with diameter 5-9 mm and 10-30 mm was 0.797 (95%CI: 0.707-0.887) and 0.809 (95%CI: 0.669-0.949), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule density, the AUC for distinguishing between benign and malignant solid nodule and subsolid nodule was 0.845 (95%CI: 0.751-0.939) and 0.790 (95%CI: 0.701-0.880), respectively, with sensitivity, specificity and accuracy reached 75% or above. Based on the analysis of nodule number, the AUC for distinguishing between benign and malignant solitary pulmonary nodule and multiple pulmonary nodule was 0.830 (95%CI: 0.696-0.965) and 0.817 (95%CI: 0.758-0.877), respectively, with sensitivity, specificity and accuracy reached 80% or above. Conclusion: The detection of EGFR gene amplification in peripheral blood rare cells contributes to the evaluation of benign and malignant pulmonary nodules, and can be used in the auxiliary diagnosis of benign and malignant pulmonary nodules.

Nested structure role in the mechanical response of spicule inspired fibers.

Euplectella aspergillummarine sponge spicules are renowned for their remarkable strength and toughness. These spicules exhibit a unique concentric layering structure, which contributes to their exceptional mechanical resistance. In this study, finite element method simulations were used to comprehensively investigate the effect of nested cylindrical structures on the mechanical properties of spicules. This investigation leveraged scanning electron microscopy images to guide the computational modeling of the microstructure and the results were validated by three-point bending tests of 3D-printed spicule-inspired structures. The numerical analyses showed that the nested structure of spicules induces stress and strain jumps on the layer interfaces, reducing the load on critical zones of the fiber and increasing its toughness. It was found that this effect shows a tapering enhancement as the number of layers increases, which combines with a threshold related to the 3D-printing manufacturability to suggest a compromise for optimal performance. A comprehensive evaluation of the mechanical properties of these fibers can assist in developing a new generation of bioinspired structures with practical real-world applications.

Effects of Three Different Heating Devices on Patients Undergoing Surgery: A Network Meta-Analysis.

PURPOSE: Perioperative hypothermia is a common anesthesia-related complication that can result in negative outcomes. Intraoperative active heating can positively impact these outcomes. Therefore this study aimed to investigate the effectiveness of three common heating devices for controlling hypothermia, improving thermal comfort, and reducing anesthesia recovery time. DESIGN: Systematic review and meta-analysis. METHODS: Seven electronic literature databases were searched from the inception date of the databases to March 18, 2022. RevMan 5.4 and Stata 15.1 were used to perform meta-analyses on the obtained data, and the Cochrane Evaluation Manual was used for quality risk assessment of the included studies. FINDINGS: A total of 18 studies involving 1,511 patients undergoing surgery using heating devices were included. In this meta-analysis, a ranking method known as the Surface Under the Cumulative Ranking Curve (SUCRA) was used. SUCRA provides a numerical measure of the effectiveness of treatments, with higher values indicating superior efficacy. Findings demonstrated that the concurrent use of three heating devices led to an elevation in core body temperatures (SUCRA = 69.2%) and enhanced delayed recovery (SUCRA = 88.6%) as compared to the application of a single device. Furthermore, for thermal comfort, the employment of heating blankets proved to be the most effective (SUCRA = 87.8%). CONCLUSIONS: This study showed the core body temperatures and reductions in delayed recovery were greater when three heating devices were used together as compared to use one of them alone. Heating blankets was the most effective option for improving the thermal comfort of patients. Thus, clinicians should opt for appropriate heating equipment according to the type of surgery and the characteristics and needs of patients. The choice of appropriate heating equipment will ensure surgical safety, improve patient comfort, and reduce surgical risks.

[Analysis of the effect and safety of lumen reshaping after endovascular repair of Stanford B type aortic dissection at different intervention times].

Objective: To Compare the effects and safety of lumen reshaping after thoracic endovascular aortic repair (TEVAR) for Stanford B type aortic dissection (AD) at different intervention times. Methods: A retrospective analysis was conducted on the clinical data of 189 patients with Stanford type B aortic dissection treated with TEVAR at the Affiliated Hospital of Chengde Medical College from January 2016 to December 2020.Based on the time from onset to surgery, patients were divided into an early intervention group (≤14 days, n=127) and a delayed intervention group (>14 days, n=62).The diameters of the total aorta, true lumen and false lumen at different times and planes (S1 plane: at the bifurcation of the pulmonary artery; S2 plane: at the lower edge of the left atrium; S3 plane: at the upper edge of the celiac trunk) post-surgery were compared between the two groups, and the rate of change in diameters of true and false lumens across these planes was calculated. The patients were followed until December 1st, 2023, and the median follow-up time was 45(40, 49) months. The postoperative complications and survival of the two groups were compared. Results: The early intervention group comprised 86 men and 41 women, with an average age of (58.3±10.7) years. The delayed intervention group included 41 men and 21 women, with an average age of (58.5±9.2) years. Both groups had an operation success rate of 100%. Six months post-surgery, the early intervention group had an expansion rate of the true lumen diameter at planes S2 and S3 of 40.1%(25.5%, 56.1%) and 5.3%(-2.5%, 15.8%), respectively, which was superior to the delayed intervention group's 18.5%(10.6%, 39.8%) and 1.0%(-8.2%, 9.6%) (both P<0.05).The early intervention group had a reduction rate of the false lumen diameter at planes S1, S2, and S3 of -56.2%(-61.3%, -48.8%), -70.4%(-81.8%, -56.6%), and -5.4%(-17.4%, 0.1%), respectively, better than the delayed intervention group's -44.2%(-53.7%, -38.3%), -49.0%(-57.6%, -35.8%), and -3.1%(-6.7%, 1.8%) (all P<0.05).At plane S1, the true lumen diameter of patients in both groups showed an increasing trend over 36 months post-surgery, while the false lumen diameter showed a decreasing trend (both P<0.05).At plane S2, the true lumen diameter of patients in the early intervention group exhibited an increasing trend over 36 months post-surgery, and the false lumen diameter exhibited a decreasing trend (both P<0.05).At plane S3, the total aortic diameter of patients in the delayed intervention group showed a slight increasing trend over 36 months post-surgery (P<0.05).The overall survival time were 45.0 months (95%CI: 42.9-47.1) for patients in the early intervention group and 46.0 months (95%CI: 43.5-48.5) for those in the delayed intervention group, with no statistically significant difference observed (P>0.05).The incidence rates of complications such as aortic rupture, retrograde Type A dissection, new distal endograft dissection, endoleak, paraplegia, and others showed no statistically significant difference between the two groups (all P>0.05), with no cases of stent migration or deformation observed. Conclusion: Early intervention for Stanford type B aortic dissection provides a better aortic remodeling outcome than delayed intervention, with similar safety.

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol.

Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA's brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression.

[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.

Decreased nicotinamide adenine dinucleotide (NAD+) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD+ precursor due to efficient NAD+ elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has not been investigated. Here, we used the isolated mouse heart allowing cardiac metabolic control to investigate: (1) whether NR can protect the isolated heart against IRI, (2) the metabolic pathways underlying NR-mediated protection, and (3) whether insulin abrogates NR protection. NR protection against cardiac IRI and effects on metabolic pathways employing metabolomics for determination of changes in metabolic intermediates, and 13C-glucose fluxomics for determination of metabolic pathway activities (glycolysis, pentose phosphate pathway (PPP) and mitochondrial/tricarboxylic acid cycle (TCA cycle) activities), were examined in isolated C57BL/6N mouse hearts perfused with either (a) glucose + fatty acids (FA) ("mild glycolysis group"), (b) lactate + pyruvate + FA ("no glycolysis group"), or (c) glucose + FA + insulin ("high glycolysis group"). NR increased cardiac NAD+ in all three metabolic groups. In glucose + FA perfused hearts, NR reduced IR injury, increased glycolytic intermediate phosphoenolpyruvate (PEP), TCA intermediate succinate and PPP intermediates ribose-5P (R5P) / sedoheptulose-7P (S7P), and was associated with activated glycolysis, without changes in TCA cycle or PPP activities. In the "no glycolysis" hearts, NR protection was lost, whereas NR still increased S7P. In the insulin hearts, glycolysis was largely accelerated, and NR protection abrogated. NR still increased PPP intermediates, with now high 13C-labeling of S7P, but NR was unable to increase metabolic pathway activities, including glycolysis. Protection by NR against IRI is only present in hearts with low glycolysis, and is associated with activation of glycolysis. When activation of glycolysis was prevented, through either examining "no glycolysis" hearts or "high glycolysis" hearts, NR protection was abolished. The data suggest that NR's acute cardioprotective effects are mediated through glycolysis activation and are lost in the presence of insulin because of already elevated glycolysis.

[Impact of COVID-19 on the treatment of sleep medicine].

The outbreak of coronavirus disease 2019 (COVID-19) has become a major threat to the global healthcare system. As an airborne disease, COVID-19 posed a great challenge to the management of sleep medicine. Given the increased risk of adverse events in obstructive sleep apnea patients infected with COVID-19, strategies have been proposed worldwide. These include standard treatment procedure, use of self-protect equipment, telemedicine services, development of machine learning and portable monitoring, and in-home sleep monitoring and titration. This review aims to introduce the impact of COVID-19 on the operation of sleep medicine landscape and provide advice on public health care emergency.

[Application of interventional respiratory techniques in the treatment of pulmonary bullae:an update].

Pulmonary bullae is a common complication of chronic obstructive pulmonary disease(COPD), causing the deterioration in lung function, leading to aggravated dyspnea and poor quality of life for patients. The traditional therapeutic approach for pulmonary bullae is bullectomy using surgical thoracoscopy. The disadvantage of this approach is the postoperative complications and high risk of recurrence in many patients. In addition, for some patients, due to the patient's physical conditions, such as poor lung function and other diseases, bullectomy could not be used. Therefore, new alternative approaches were urgently needed. In recent years, interventional respiratory technology has been trialed to treat pulmonary bulla all around the world and has achieved great success. In this paper, we reviewed the relevant clinical research progress of interventional respiratory medicine techniques in the treatment of pulmonary bullae.

[Research on the origin and development of "Wu shan qi e"].

"Wu shan qi e"(five symptoms with good prognosis and seven with poor prognosis)is a theory used to determine the prognosis of external diseases in traditional Chinese medicine which have been mentioned in many ancient Chinese medicine books and have been valued by external doctors throughout history. However, it has been rarely discussed in modern literature. The theory were first seen in the Taiping Shenghui Fang, and the idea was originated from Ni Shun in Lingshu Yuban."Wu shan qi e"have evolved into many variants through the exertion of medical practitioners throughout history. By reviewing medical books of previous dynasties, it was found that there are two main versions: the Taiping Shenghui Fang version and its derivative versions, and the Waike Zhengzong version and its derivative versions.

Psychological Distress and Behavioral Vigilance in Response to Minority Stress and Threat among Members of the Asian American and Pacific Islander Community during the COVID-19 Pandemic.

Stigmatization, hostility, and violence towards the Asian American and Pacific Islander (AAPI) community have increased sharply during the COVID-19 pandemic. It is important to conduct research to promote understanding of the effects of such stigmatization on the AAPI community. Accordingly, the present study used a combined minority stress and integrated threat framework to examine whether factors related to AAPI identity would moderate the relationship between stigmatization/threat associated with AAPI identity and increased psychological distress and behavioral vigilance. AAPI individuals were recruited online from both Turk Prime and Reddit and completed measures of perceived stigmatization; integrated threat; depression, anxiety, and stress; and behavioral vigilance. Perceptions of stigmatization and threat predicted relevant outcomes both as individual predictors and in multivariate analyses. However, factors relating to the strength of AAPI identification did not moderate the effects of stigmatization and threat on psychological distress and behavioral vigilance, which is a result that failed to support this aspect of the broader conceptual model on which this project was based. Instead, these proposed moderators were themselves predicted by stigmatization and threat variables. The implications of these findings for effective interventions to alleviate the negative consequences of anti-Asian stigmatization are discussed.

[Diagnosis and treatment of arrhythmogenic cardiomyopathy in children].

Objective: To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children. Methods: A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022. Results: A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable. Conclusions: ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.