[摘 要] 甲状腺癌是内分泌系统中最为常见的恶性肿瘤，近年来其发病率呈现出显著的上升趋势。乙酰化修饰作为一种重要的蛋白质翻译后修饰，参与调控各个类型甲状腺癌相关基因的转录表达、细胞周期进程及侵袭能力。组蛋白去乙酰化酶（HDAC）抑制剂在甲状腺癌治疗中显示出潜在的应用前景。本文通过调研近年来相关文献，系统回顾了乙酰化修饰在参与甲状腺癌发生发展过程中的生物学功能及其调控机制，进一步探讨HDAC抑制剂在临床治疗中的应用前景，为甲状腺癌的靶向治疗提供坚实的理论依据和提出可行的治疗策略。

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

Crotonylation is a protein post-translational acylation modification, although mainly focused on histones, but more and more studies have found that non-histone crotonylation modifications can participate in important biological functions of the human body. By investigating the relevant literature in recent years, this paper systematically elaborates the content of non-histone crotonylation modification. Firstly, the regulatory mechanism of crotonylation, that is, the transfer of crotonyl groups on protein lysine regulated by multiple enzyme systems, was elucidated. Secondly, it is described that non-histone proteins with crotonylation can participate in biological processes such as DNA damage response, cell proliferation, myogenic differentiation, and tissue fibrosis. This article aims to provide a theoretical basis for subsequent non-histone crotonylation research by reviewing the regulation and disease aspects of non-histone crotonylation modification in recent years, and to explore new methods for the clinical prevention and treatment of related diseases.

Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.

Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Pelvic Exenteration ; Biological Products/therapeutic use* ; Pelvic Floor/pathology* ; Neoplasm Recurrence, Local/surgery* ; Rectal Neoplasms/surgery* ; Postoperative Complications/prevention & control* ; Retrospective Studies ; Treatment Outcome

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Objective:To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer. Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D 2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow-up. Propensity score matching was done by the 1∶1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curves, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them ( χ2=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20?600)mL, 5, 3.0(range, 2.0?10.0)days, 4.0(range, 2.0?12.0)days, 9.0(range, 4.0?31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20?500)mL, 4, 3.5(range, 1.0?14.0)days, 4.0(range, 2.0?15.0)days, 8.0(range, 5.0?45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups ( t=1.13, Z=?0.37, χ2=0.12, Z=?1.26, ?0.33, ?0.70, χ2=1.01, Z=?1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R 0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0?28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0?31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups ( Z=?3.39, ?2.55, ?3.12, χ2=6.60, P<0.05). (5) Follow-up. Of the 154 patients, 143 patients were followed up for 37(range, 5?69)months. The 3-year overall survival rate and 3-year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups ( χ2=0.14, 0.60, P>0.05). Conclusions:Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D 2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.