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The process of acetylation and deacetylation of histones within the nucleus operates within a dynamic equilibrium. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) collaboratively and precisely regulate normal gene transcription and expression. Any disorder in the activity of HATs/HDACs can lead to uncontrolled gene expression, consequently resulting in tumorigenesis. Histone deacetylase inhibitors (HDACIs) have the capacity to block the cell cycle, thereby restraining tumor cell proliferation and tumor growth. Also, HDACIs exhibit a significant capability to diminish the expression of apoptosis protein inhibitors such as Bcl-2 and B-cell lymphoma-extra-large (Bcl-xL), while concurrently up-regulating pro-apoptotic proteins such as Bax, Bad, and Bim. Also, HDACIs demonstrate the ability to inhibit tumor cell angiogenesis. Representing a new category of targeted anti-cancer therapeutics, HDACIs possess the capability to restore the expression of tumor suppressor genes, induce apoptosis, and stimulate cell differentiation. Additionally, they exert anti-cancer effects through diverse pathways both in vivo and in vitro, thereby presenting promising prospects in tumor therapy. This review delves into the involvement of HDACs in cancer pathology and the therapeutic potential of HDACIs as emerging drugs in cancer treatment. [ABSTRACT FROM AUTHOR]

Spin-dependent transport in ferromagnet/organic-ferromagnet/ferromagnet junctions is investigated theoretically under different alignment of magnetization orientations. The results demonstrate a significant current rectification at low bias voltages, and the rectifying direction relies on the relative magnetization orientation in each component. The orbital analysis demonstrates two underlying mechanisms for the rectification, the slight structural asymmetry of the molecule from spin radicals and distinct spin match between conducting electrons and the magnetic molecule upon the reversal of bias. The latter is responsible for the strong low-bias rectification and relies on the magnetization alignment. The effects of parameter strength, temperature and size on the rectification are discussed. This work explores a new route to achieve high-performance molecular rectifiers operating at low bias with controlled rectifying direction. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the protein requirements of growing Fuxing pig, and to provide basic parameters for determining the feeding standards of growing Fuxing pig. In this experiment, a single factor randomized block design was used, and forty healthy weaned pigs with a body weight of(20.45±1.65kg)were randomly selected and divided into 4 groups, with 10 pigs in each group. Each group was fed diets with CP levels(CP12CP14CP16CP18)during the 67 days feeding trail, the 7 days preliminary experimental period and the 60 days experimental period. Three healthy pigs were randomly selected from each group. Before the last 7 days of the experiment, all urine and feces were collected to determine the nutritional digestibility and metabolic. The results showed that the addition of CP16 to the diet could reduce the F/G. The CP16 group decreased by 8%, 6.9%, and 3.7% compared with that of the CP12, CP14, and CP18 groups, respectively. There was no difference between the CP16 and CP18 groups (P>0.05). The digestibility of EE in the CP16 and CP18 groups was significantly higher than that in the CP12 group (P≤0.05). There was no significant difference between the CP14, CP16, and CP18 groups (P>0.05). With the increase of the crude protein level, the digestibility of EE in the CP, DCP (digestible crude protein) CP16and CP18 groups was significantly higher than that of the CP12 group, CP14 group (P≤0.01), CP16 group. In the case of the CP12 group and the CP14 group, NI (nitrogen intake), UN (urine nitrogen), RN (retention nitrogen), N%, were all significantly higher. To sum, Fuxing pig DCP intake was used as the dependent variable (Y) and ADG as the independent variable (X) for linear regression analysis. The digestible CP requirement the regression equation with Fuxing pig's growing period was as follows: DCP=1.93 W0.75+0.34W (DCP: g/d;W0.75: kg;W: g/d). [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical characteristics of intermittent exotropia (IXT) patients with different visual perception and oculomotor control. Methods: A cross-sectional study was conducted. Minor IXT patients between March 2021 and May 2023 at Beijing Tongren Hospital were enrolled. Demographic characteristics were recorded, and visual perception and oculomotor control were evaluated. The patients were divided into simultaneous vision disappearing and existing groups, fusion disappearing and existing groups, distant stereoscopic vision disappearing and normal groups, and near stereoscopic vision injury and normal groups. Statistical description was performed by using M ( Q 1 , Q 3 ). Rank sum test was used to compare the Revised Newcastle Control Score (RNCS), near and far strabismus degree, duration of disease, and age of onset among different groups. The correlation between visual perception and oculomotor control and the correlation of duration of disease and age of onset with visual perception and oculomotor control were analyzed by Pearson correlation analysis. Results: A total of 381 patients were enrolled, including 189 males and 192 females, with a median age of 7 (6, 9) years. The incidence of normal visual perception was 19.4% (74/381). Compared with simultaneous vision and fusion existing groups and distant and near stereoscopic vision normal groups, the RNCS [7 (5, 9) vs 4 (3, 6), 6 (5, 8) vs 4 (3, 6), 5 (4, 7) vs 3 (3, 5), and 5 (3, 6) vs 4 (3, 6)], near strabismus degree [65 Δ (60 Δ , 80 Δ ) vs 40 Δ (30 Δ , 50 Δ ), 60 Δ (45 Δ , 65 Δ ) vs 40 Δ (30 Δ , 50 Δ ), 50 Δ (40 Δ , 60 Δ ) vs 35 Δ (30 Δ , 45 Δ ), and 45 Δ (30 Δ , 60 Δ ) vs 40 Δ (30 Δ , 50 Δ )] and far strabismus degree [60 Δ (50 Δ , 75 Δ ) vs 35 Δ (25 Δ , 50 Δ ), 55 Δ (41 Δ , 65 Δ ) vs 35 Δ (25 Δ , 45 Δ ), 45 Δ (30 Δ , 60 Δ ) vs 35 Δ (25 Δ , 45 Δ ), and 40 Δ (30 Δ , 60 Δ ) vs 35 Δ (25 Δ , 45 Δ )] increased significantly in disappearing simultaneous vision, fusion, and distant stereoscopic vision groups and injury near stereoscopic vision group (all P <0.05). Compared with simultaneous vision and fusion existing groups and distant stereoscopic vision normal group, duration of disease was significant longer in disappearing simultaneous vision, fusion, and distant stereoscopic vision groups [3 (1, 5) years vs 2 (1, 3) years, 2 (1, 4) years vs 1 (1, 3) years, 2 (1, 4) years vs 1 (1, 3) years, all P <0.05]. The age of onset in disappearing distant stereoscopic vision group was significantly lower than normal distant stereoscopic vision group [5 (3, 7) years vs 6 (4, 8) years, P =0.005]. Pearson correlation analysis showed that subjective angle and random dot stereogram (RDS) stereoacuity were positive correlation with RNCS, and the near and far strabismus degree ( r =0.414, 0.516, and 0.559, all P <0.001; r =0.153, 0.142, and 0.173, all P <0.05). Subjective angle, RNCS, and the near and far strabismus degree were positive correlation with duration of disease ( r =0.238, 0.195, 0.236, 0.239, all P <0.001) and negative correlation with age of onset ( r =-0.184, -0.279, -0.112, -0.147, all P <0.05). Conclusions: Nearly 20% of IXT patients have normal visual perception. With the longer duration of disease or lower age of onset, the incidence of abnormal visual perception is higher and injury of visual perception and oculomotor control is more serious.

Objective: To establish a Plaque-reduction Neutralization Test (PRNT) for the detection of neutralizing antibody titers of Human Respiratory Syncytial Virus (HRSV) and optimize the conditions for preliminary application. Methods: The CHO expression system was used to produce palivizumab monoclonal antibody (palivizumab) and the influencing factors such as cell type, cell culture duration, fixation and permeabilization protocols, and blocking agents. The reproducibility of the method was verified and its correlation was verified with conventional PRNT. Finally, the optimized PRNT assay was further used to determine neutralizing antibody titers against HRSV subtypes A and B in BALB/c mouse serum (immunized by intramuscular injection of HRSV fusion proteins). Results: Palivizumab was expressed at approximately 50 mg/L. The optimal working conditions for PRNT were as follows: culturing HEp-2 cells for 2 days, fixing with 4% (V/V) paraformaldehyde at room temperature for 15 min followed by 0.2% (V/V) Triton X-100 permeabilization for 15 minutes as the optimal fixation-permeabilization and removing the blocking step. The overall coefficient of variation (CV) for the reproducibility validation of this method was <15%, showing a good linear relationship with the conventional PRNT. The Spearman correlation coefficient r s was 0.983. This method was used to detect neutralizing antibody titers in mouse sera against HRSV subtype A strain long and subtype B strain 9320, and the fusion proteins combined with AlOH and CpG adjuvant induced the highest neutralizing antibody titers in mice. Conclusion: The HRSV neutralizing antibody assay established in this study is rapid, reproducible, high-throughput, and can be used to detect neutralizing antibodies to HRSV subtypes A and B.

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P ＜0.001; 77.78% vs 16.84% for bone metastasis, P ＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P =0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P =0.002; 44.83% vs 20.23 % for bone metastasis, P =0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P =0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P =0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P =0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P =0.019; 8.03 months vs 19.50 months for OS, P =0.019, P =0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P =0.004; 11.2 months vs 20.60 months for OS, P =0.019). Multivariate analysis showed that disease stage ( HR =2.806, 95% CI: 1.499-5.251, P =0.001) and DTCs quantity detected by SE-iFISH ( HR =1.841, 95% CI: 1.095-3.095, P =0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR =2.538, 95% CI: 1.169-5.512, P =0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Objective: To evaluate the effects of obesity on the incidence of postoperative pulmonary complications (PPCs) following laparoscopic colorectal surgery. Methods: A total of 150 patients with pathological diagnosis of colorectal cancer who accepted laparoscopic colorectal excision from January to May 2023 were retrospectively recruited. All the patients scored 26 points or more in the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) model, making them all in intermediate to high risks of PPCs. Patients were divided into obesity group and non-obesity group depending on whether they were obese or not. Propensity score matching (1∶1) was performed to achieve the balance of clinicopathological characteristics with the matching factors of age, sex, respiratory complications and ARISCAT score. A total of 96 patients were eventually enrolled, with 48 patients in obesity group and 48 patients in non-obesity group. Besides, the patients were divided into 25°-30° Trendelenburg subgroup and ±10°-15° Trendelenburg subgroup according to surgical sites for further analysis. The incidence of PPCs, the intraoperative airway pressure and blood biomarker expression of lung injury, including soluble receptor for advanced glycation end products (sRAGE) and angiopoietin-2 (ANG2) at postoperative day (POD) 1 and POD3 between the two groups were compared. The relationship between obesity and incidence of PPCs within 30 postoperative days were analyzed with unifactorial Cox proportional hazard model. Results: The obesity group was comprised of 35 males and 13 females with a median age of 60 (49, 69) years, and the non-obesity group was comprised of 35 males and 13 females with a median age of 60 (52, 67) years. The incidence of PPCs was 50.0% (24/48) in the obesity group, which was higher than 20.8% (10/48) in the non-obesity group and the incidence of grade Ⅰ PPCs and microatelectasis were 31.3% (15/48) and 33.3% (16/48), higher than the 12.5% (6/48) and 12.5% (6/48) of the non-obesity group (all P <0.05). The peak airway pressure (Ppeak) and plateau airway pressure (Pplat) of patients in obesity group were 34.0(31.5, 36.5) and 30.0(27.0, 32.0) cmH 2 O(1 cmH 2 O=0.098 kPa), which were significantly higher than the 26.0 (24.0, 29.5) and 22.0 (21.0, 26.5) cmH 2 O of the non-obesity group (all P <0.001). The ANG2 level of the obesity group at POD3 was 11.9 (8.4, 16.5) μg/L, which was higher than 9.2 (6.0, 12.3) μg/L of the non-obesity group ( P =0.045). In 25°-30°Trendelenburg subgroup, the incidence of PPCs in obese patients were significantly higher than that of non-obese patients [41.4% (12/29) vs 11.4% (4/35), P =0.005]. In ±10°-15°Trendelenburg subgroup, no significant difference was found in PPCs incidence between obese and non-obese patients [63.2% (12/19) vs 46.2% (6/13), P =0.215]. The unifactorial Cox proportional hazard model analysis showed that obesity was a risk factor of PPCs in 30 postoperative days ( HR =3.015, 95% CI : 1.438-6.321, P =0.001). Conclusion: In patients undergoing laparoscopic colorectal surgery with intermediate to high risk of PPCs, obesity raises intraoperative airway pressure and aggravates intraoperative lung endothelial injury. Obesity is a risk factor of PPCs in 30 postoperative days.

Objective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group ( n =24) and operation group ( n =24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged ( P =0.035), and the residence time in the target quadrant was reduced ( P =0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1β, IL-6 and TNF-α between the two groups (all P >0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.

Objective: To investigate the effect of deep neuromuscular blockade (DNMB) combined with low pneumoperitoneum pressure anesthesia strategy on postoperative pain in patients undergoing laparoscopic colorectal surgery. Methods: This study was a randomized controlled trial. One hundred and twenty patients who underwent laparoscopic colorectal surgery at Cancer Hospital of Chinese Academy of Medical Sciences from December 1, 2022 to May 31, 2023 were selected and randomly divided into two groups by random number table method. Moderate neuromuscular blockade [train of four stimulations count (TOFC)=1-2] was maintained in patients of the control group (group C, n =60) and pneumoperitoneum pressure level was set at 15 mmHg(1 mmHg=0.133 kPa). DNMB [post-tonic stimulation count (PTC)=1-2] was maintained in patients of the DNMB combined with low pneumoperitoneum pressuregroup (group D, n =60) and pneumoperitoneum pressure level was set at 10 mmHg. The primary measurement was incidence of moderate to severe pain at 1 h after surgery. The secondary measurements the included incidence of moderate to severe pain at 1, 2, 3, 5 d and 3 months after surgery, the incidence of rescue analgesic drug use, the doses of sufentanil in analgesic pumps, surgical rating scale (SRS) score, the incidence of postoperative residual neuromuscular block, postoperative recovery [evaluated with length of post anesthesia care unit (PACU) stay, time of first exhaust and defecation after surgery and length of hospital stay] and postoperative inflammation conditions [evaluated with serum concentration of interleukin (IL)-1β and IL-6 at 1 d and 3 d after surgery]. Results: The incidence of moderate to severe pain in group D 1 h after surgery was 13.3% (8/60), lower than 30.0% (18/60) of group C ( P <0.05). The incidence of rescue analgesia in group D at 1 h and 1 d after surgery were 13.3% (8/60) and 4.2% (5/120), respectively, lower than 30.0% (18/60) and 12.5% (15/120) of group C (both P <0.05). The IL-1β level in group D was (4.1±1.8)ng/L at 1 d after surgery, which was lower than (4.9±2.6) ng/L of group C ( P =0.048). The IL-6 level in group D was (2.0±0.7)ng/L at 3 d after surgery, which was lower than (2.4±1.1) ng/L of group C ( P =0.018). There was no significant difference in the doses of sufentanil in analgesic pumps, intraoperative SRS score, incidence of neuromuscular block residue, time spent in PACU, time of first exhaust and defecation after surgery, incidence of nausea and vomiting, and length of hospitalization between the two groups (all P >0.05). Conclusion: DNMB combined with low pneumoperitoneum pressure anesthesia strategy alleviates the early-stage pain in patients after laparoscopic colorectal surgery.