ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

Objective:To evaluate the safety and effectiveness of laparoscopic ventral mesh rectopexy (LVMR) +anal sphincter plasty for complete rectal prolapse.Methods:From Jan 1, 2018 to Dec 31, 2022, 45 patients with complete rectal prolapse diagnosed in Beijing Erlong Road Hospital received laparoscopic ventral mesh rectopexy +anal sphincter plasty were included in this study.Result:There was no mortality rate associated with LVMR in this study cohort. The follow-up period was 8-76 months, with a median follow-up period of 59 months. There were 2 cases of recurrence, with a recurrence rate of 4%. Patients with concomitant fecal incontinence symptoms had a preoperative Jorge Wexner fecal incontinence score of 13.8±2.0, and postoperative Jorge Wexner fecal incontinence scores of 7.5±1.5, 5.3±1.3, 4.3±1.1, 2.8±1.0, and 1.8±0.5 at 3, 6, 12, 36, and 60 months, respectively, all P<0.001. Patients with concomitant constipation had a preoperative Wexner constipation score of 15.7 ± 1.5, and a postoperative Wexner constipation score of 9.0±1.8, 6.8±1.5, 5.2±1.4, 4.1±0.7, 2.0±0.0 at 3, 6, 12, 36, and 60 months, respectively, all P<0.001. Conclusions:LVMR +anal Sphincter plasty is safe and effective for the treatment of complete rectal prolapse, and there are few complications related to biological patches. Anal sphincter plasty can effectively improve anal function.

Objective:To analyze the effect of perioperative SEPT9 level in peripheral blood on long-term prognosis of patients with colorectal tumors. Methods:Retrospectively analyzed the data of 334 patients with colorectal cancer admitted to the Department of Anus & Intestine Surgery from January 2017 to December 2022, including 197 male patients and 137 female patients, aged 29 to 83 (62.8±10.7) years. Positive group was consisted of 241 patients with positive SEPT9 before surgery, while negative group was consisted of 93 patients with negative SEPT9 before surgery. Among the positive group, 169 cases turned negative for SEPT9 on the one week after surgery (transnegative group), and another 72 cases did not turn negative (non negative group). Univariate and multivariate analysis of clinical general data were carried out to screen out the risk factors affecting the long-term prognosis of colorectal cancer patients after surgery. The survival curve was calculated by Kaplan-Meier method, and the Log-rank test was used to compare the difference in survival rate between groups. Results:All patients′ overall median survival time was 67 months, and the 1, 3 and 5 years overall survival rate was 91.9%, 70.9% and 57.1%. The results of multi-factor analysis showed that whether the tumor had lymph node metastasis, TNM stage, and preoperative SEPT9 methylation status were independent risk factors affecting the long-term prognosis of colorectal cancer ( P=0.004, <0.001, 0.041), while for patients with preoperative SEPT9 positive, TNM stage of tumor and whether SEPT9 turned negative after surgery were independent risk factors for prognosis ( P=0.026, 0.001). The median survival time of patients in positive group and negative group was 63 months and 71 months, respectively. The 1, 3 and 5 year survival rates after surgery were 90.4%, 67.0%, 55.0% and 95.7%, 79.1% and 64.6%, respectively( P=0.007). The median survival time of the patients in the transnegative group and nonnegative group was 45 months and 62 months, respectively. The 1, 3 and 5-year survival rates were 83.2%, 60.5%, 48.1% and 93.5%, 72.9%, 63.5%( P<0.001). Conclusions:Perioperative SEPT9 level is correlated with long-term prognosis of CRC patients, and patients with negative SEPT9 before surgery have better prognosis than those with positive SEPT9. Preoperative positive patients who do not turn negative after surgery often indicate poor prognosis of tumor.

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.

Background Although transforming growth factor-β (TGF-β)/Smad signaling pathway is important in regulating the occurrence and development of pulmonary fibrosis, the pathogenesis of pulmonary fibrosis remains elusive. Objective To explore the functions of genes associated with TGF-β/Smad signaling pathway in the progression of pulmonary fibrosis. Methods A NIH-3T3 fibroblast model induced by TGF-β1 was established. The experiment samples were divided into a control group and a TGF-β1 treatment group. The control group was exposed to normal saline, while the TGF-β1 treatment group was exposed to 10 ng·mL⁻¹ TGF-β1 for 12 h. The RNAs of the two groups were extracted, sequenced, and analyzed by bioinformatics methods to identify seven key genes in TGF-β pathway, including Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3. The gene expression levels of five markers [Collagen1α1, Collagen1α2, α-smooth muscle actin (α-SMA), TGF-β1, and TGF-β3] and the seven key genes were detected by quantitative real-time PCR (qRT-PCR). The proteins of the two groups were extracted. The important marker protein expression levels of Smad3, the phosphorylation of Smad3 (P-Smad3), and α-SMA were detected by Western blotting. At the same time, 30 healthy SPF-grade C57BL/6 mice were randomly divided into three groups, with 10 mice in each group: a control group, a SiO₂ inhalation exposure group for 28 d (10 mice), and a SiO₂ inhalation exposure group for 56 d (10 mice). The mice in the two treatment groups were exposed to a natural SiO₂ environment for 4 h per day with a 10-min pause for breathing fresh air at 2 h intervals. The lung tissues of the mice were taken after execution. The changes of pulmonary fibrosis were detected by Masson staining, and mRNAs and proteins were extracted to detect the expression of the above key genes and proteins. Results The expression levels of the five marker genes Collagen1α1, Collagen1α2, α-SMA, TGF-β1, and TGF-β3 were significantly increased in the TGF-β1-induced NIH-3T3 fibroblasts than those in the control group (P < 0.01); the expression levels of P-Smad3 and α-SMA proteins increased significantly (P < 0.01); the expression results of the seven key genes screened in the TGF pathway were that Dcn and Smad3 were obviously down-regulated (P < 0.01), and Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 were obviously up-regulated (P < 0.01). The changes in gene expression levels of the transcriptome sequencing showed the same trend. The results of Masson staining showed that the content of collagen fibers in the lung tissues also increased in the SiO₂ inhalation exposure groups over time. In the mouse experiment, five marker genes were obviously up-regulated compared with the control group (P < 0.01); no obvious change was found in the expression of Smad3 protein, and the expression levels of P-Smad3 and α-SMA were obviously higher in the SiO₂ exposure groups than those in the control group (P < 0.01); the expression levels of Dcn and Smad3 showed a down-regulated trend, while the expression levels of Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 showed an up-regulated trend with the increase of SiO₂ inhalation exposure days (P < 0.01). The expression levels of the above five marker genes, three important marker proteins, and seven key genes were consistent with the expression trends of TGF-β1-induced NIH-3T3 fibroblasts. Conclusion The expression levels of pulmonary fibrosis-related marker genes and proteins change significantly in TGF-β1-induced fibroblast cells, and the lung tissues of mice under natural SiO₂ inhalation exposure has obvious fibrosis characteristics. Seven genes (Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3) may be involved in the regulation of pulmonary fibrosis by the TGF-β/Smad signaling pathway.

Objective: To study the effects of different concentrated sulfuric acid etching durations on the shear bond strength between polyether-ketone-ketone (PEKK) and dentin, providing a scientific basis for the clinical bonding procedures of PEKK prosthesis. Methods: Forty-four PEKK specimens were prepared and randomly divided into four groups: group A was the control group, which was only polished with abrasive papers, group B, group C and group D were experimental groups, which were etched by 98% concentrated sulfuric acid for 5 s, 30 s and 60 s, respectively. In addition, one sample was randomly selected from each group, and the profile was prepared by a slow cutting machine. The surface morphology of the profile was observed under SEM. After the four groups of specimens and dentin were bonded by resin, they were soaked in distilled water at 37 ℃ for 24 h. After the shear bonding strengths were measured, the fracture interfaces of the specimens were examined by the scanning electron microscopy and stereomicroscopy, and failure models of bonding were analyzed. Results: After acid etching treatments, the cross-sectional images in group B presented uniform spongy shapes, while the cross-sectional images in group C and group D showed destructive pore structures. The shear bond strengths of group B (16.84 ± 1.84) MPa, group C (12.33 ± 1.22) MPa and group D (6.44 ± 1.18) MPa were higher than that of group A (3.99 ± 1.06) MPa (P < 0.05). The highest shear bond strength was observed in group B (16.84 ± 1.84) MPa. Conclusion The surface treatment of 98% sulfuric acid etching for 5 s manifested the best bond strength between PEKK and dentin.

Objective To evaluate the clinical efficacy of modified Bascom cleft lift procedure in the treatment of chronic sinus.Methods Modified Bascom cleft lift procedure was performed in 53 patients admitted from Oct 2012 to Jul 2016.49 cases were male and 4 were female.The average age was (25.4± 2.3) years.Results All patients were satisfied with the operation.There were 49 cases of primary healing and 4 cases of incision complications.The average follow-up was (12.1 ±4.3) months,no recurrence was observed.Conclusion The modified Bascom cleft lift technique is effective and reliable,with less complications and a lower recurrence rate.

Objective To evaluate video-assisted anal fistula treatment (VAAFT) for Parks type Ⅱ anal fistula.Methods 40 Parks type Ⅱ anal fistula patients underwent VAAFT procedure from June 2015 to June 2017.Results were compared with 40 cases treated by incision and thread drawing.Results There was no significant difference between the two groups for curative effect,postoperative urinary retention,wound edema,bleeding and recurrence rate after 6 months of operation (90％ vs.95％,x2 =0.722,P =0.697;5％ vs.8％,x2 =0.213,P=1.0;2％ vs.8％,x2 =1.053,P=0.615;0 vs.5％,x2 =2.051,P =0.494;10％ vs.5％,x2 =0.721,P =0.675).Pain on first day and one week after operation in the VAAFT was less [(1.9±0.6) vs.(3.7±1.0),t =9.438,P=0.001;(0.9±0.7) vs.(1.9±0.8),t=6.269,P=0.001],hospital stay was shorter [8.4 ±1.3) d vs.(9.2 ±2.2) d,t =2.030,P=0.047],wound healing was faster [(27 ±8) dm.(38 ±6) d,t =7.328,P =0.001].The Jorge-Wexner incontinence score [(0.5±0.7) vs.(1.2±1.3),t =2.951,P=0.005] and the fecal incontinence severity index [(1.1±1.6) vs.(5.1 ±3.2),t =7.097,P=0.001] were lower in patients receiving VAAFT procedure.Conclusion Video-assisted anal fistula treatment is a safe and effective surgical method with the advantages of less trauma,and pain,quicker recovery and no damage to the anal sphincter.

BACKGROUND: Total hip arthroplasty is a commonly used treatment, but it is difficult to accurately determine the position of the pelvis, which is easy to cause pelvic displacement postoperatively. Additionally, the implant is likely to present with angle deviation, and the precise location and direction of prosthesis is difficult to identify.OBJECTIVE: To study the position and biomechanical characteristics of prosthesis in total hip arthroplasty.METHODS: (1) One male volunteer received CT examination, and a finite element model of the pelvic was established.Three acetabular placement positions (abduction angles of 0°, 20° and 25° combined with anteversion angles of 35°, 15°and 10°) were used to perform total hip arthroplasty, and the peak von Mises stress was detected under a load of 240 N.(2) Six cadaver specimens were collected and received the same interventions with the former experiment, and the stress changes at the bone cortex surrounding femoral shaft and acetabular anterior and posterior wall were measured using resistance strain technology.RESULTS AND CONCLUSION: (1) The peak von Mises stress in the acetabulum at abduction angle of 25° combined with anteversion angle of 10° increased by 25.7%. The peak von Mises stress in the acetabular cup at abduction angles of 0°, 20° and 25° combined with anteversion angles of 35°,15° and 10° was 135.21, 68.3 and 134.2 MPa, respectively.The peak von Mises stress in the lining at abduction angles of 0°, 20° and 25° combined with anteversion angles of 35°,15° and 10° was 6.8, 3.9 and 6.7 MPa, respectively. The peak von Mises stress in the femoral shaft at abduction angles of 0°, 20° and 25° combined with anteversion angles of 35°,15° and 10° was 127.1, 100.2 and 128.2 MPa,respectively. (2) The stress at the bone cortex surrounding femoral shaft and acetabular anterior and posterior wall at abduction angles of 0° and 25° combined with anteversion angles of 35° and 10° was significantly higher than that at abduction angle of 20° combined with anteversion angle of 15°. To conclude, an abduction angle of 20° combined with anteversion angle of 15° is conductive for functional recovery of the joint.