Functional constipation （FC） is a common functional disorder of the intestines， mainly characterized by reduced bowel movement frequency， difficulty in defecation， a sensation of incomplete evacuation， and hard stools， which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids， as endogenous natural laxatives， promote bowel movements by enhancing colonic secretion and regulating intestinal motility； meanwhile， gut microbiota influence colonic transit function by regulating the enteric nervous system， immune system， and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism， this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine （TCM） in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs （such as Atractylodes macrocephala）， isolated compounds （such as Platycodon grandiflorum polysaccharides）， herbal formulas （such as Shanger huang pill）， acupuncture， and moxibustion can up-regulate the abundance of beneficial bacteria， reshape the microbial structure， correct bile acid metabolism， and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.

low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

Objective:To evaluate the safety and efficacy of the TiRobot assisted screw placement in patients with lumbar degenerative diseases.Methods:The clinical data of 165 patients with lumbar degenerative diseases from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyze, and all patients were treated with posterior lumbar decompression and instrumentation. Among them, 46 patients were used the TiRobot assisted screw placement during surgery (robotic-assisted group), and 119 patients underwent freehand screw placement by C-arm X-ray machine fluoroscopy (freehand group). The operation time, intraoperative blood loss, complication and skelalgia visual analogue scale (VAS), Oswestry disability index (ODI) before and after operation were recorded. The accuracy of screw placement and rate of proximal facet joint violation were compared between two groups.Results:There were no statistical difference in operation time, intraoperative blood loss and incidence of complication between two groups ( P>0.05). In the two groups, the 3 d VAS and ODI after operation were significantly lower than those before operation, robot-assisted group: (3.33 ± 1.40) scores vs. (6.54 ± 2.00) scores and (16.96 ± 8.03) scores vs. (43.09 ± 5.48) scores; freehand group: (3.56 ± 1.29) scores vs. (6.55 ± 1.65) scores and (18.89 ± 6.74) scores vs. (44.91 ± 4.96) scores, and there were statistical differences ( P<0.01); there were no statistical difference in VAS and ODI before operation and 3 d after operation between two groups ( P>0.05). A total of 234 screws were implanted in robot-assisted group, and 590 screws were implanted in freehand group. The accuracy of screw placement in robot-assisted group was significantly higher than that in freehand group: 80.77% (189/234) vs. 74.58% (440/590), the rate of proximal facet joint violation was significantly lower than that in freehand group: 2.56% (6/234) vs. 7.29% (43/590), and there were statistical differences ( χ2 = 3.56 and 6.68, P<0.05). Conclusions:The TiRobot assisted screw placement for lumbar degenerative diseases is safe and effective. Compared to freehand technique, the TiRobot assisted method demonstrates higher screw placement accuracy and a lower rate of proximal facet joint violation.

Objective:To explore the feasibility and adaptability of laparoscopy in the surgical treatment of splenic aneurysm.Methods:The data of 28 patients with splenic aneurysms who underwent laparoscopic surgery in the Department of Hepatobiliary and Pancreatic Surgery of the Third Affiliated Hospital of Soochow University from January 2010 to December 2023 were retrospectively collected and analyzed. Among them, there were 13 males and 15 females, with the age of (57.3±7.7) years. All patients underwent laparoscopic splenic aneurysm resection, and whether to perform splenic artery anastomosis or splenectomy was determined based on the intraoperative situation. Collect the long diameter and location of splenic aneurysms, intraoperative blood loss, operation time, postoperative complications (bleeding, pancreatic fistula, splenic infarction, and splenic vein and portal vein thrombosis), postoperative hospital stay and hospitalization expenses of the patients.Results:All patients successfully underwentlaparoscopic surgery for splenic aneurysms. Aneurysms were located at the origin of the splenic artery in 3 cases (10.7%), in the middle in 8 cases (28.6%), and at the tail in 17 cases (60.7%). The long diameter of the aneurysms was (3.1±1.7) cm. Among the 28 patients, 18 cases (64.3%) underwent splenic aneurysm resection alone, 5 cases (17.9%) underwent splenic aneurysm resection combined with end-to-end anastomosis of the splenic artery, and 5 cases (17.9%) underwent splenic aneurysm resection combined with splenectomy. The operation time of 28 patients was (124.3±55.1) min, the intraoperative blood loss was 100.0 (50.0, 162.5) ml, the postoperative hospital stay was (10.9±3.8) days, and the hospitalization cost was (3.7±1.2) wanyuan. Among the 28 patients, 5 cases (17.9%) developed pancreatic fistula, 1 case (3.6%) had partial splenic infarction, and 1 case (3.6%) had portal vein and splenic vein thrombosis after the operation.Conclusion:Laparoscopic surgery for splenic aneurysm is safe and feasible, with less surgical trauma and quick postoperative recovery.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.

Objective:To explore the feasibility and adaptability of laparoscopy in the surgical treatment of splenic aneurysm.Methods:The data of 28 patients with splenic aneurysms who underwent laparoscopic surgery in the Department of Hepatobiliary and Pancreatic Surgery of the Third Affiliated Hospital of Soochow University from January 2010 to December 2023 were retrospectively collected and analyzed. Among them, there were 13 males and 15 females, with the age of (57.3±7.7) years. All patients underwent laparoscopic splenic aneurysm resection, and whether to perform splenic artery anastomosis or splenectomy was determined based on the intraoperative situation. Collect the long diameter and location of splenic aneurysms, intraoperative blood loss, operation time, postoperative complications (bleeding, pancreatic fistula, splenic infarction, and splenic vein and portal vein thrombosis), postoperative hospital stay and hospitalization expenses of the patients.Results:All patients successfully underwentlaparoscopic surgery for splenic aneurysms. Aneurysms were located at the origin of the splenic artery in 3 cases (10.7%), in the middle in 8 cases (28.6%), and at the tail in 17 cases (60.7%). The long diameter of the aneurysms was (3.1±1.7) cm. Among the 28 patients, 18 cases (64.3%) underwent splenic aneurysm resection alone, 5 cases (17.9%) underwent splenic aneurysm resection combined with end-to-end anastomosis of the splenic artery, and 5 cases (17.9%) underwent splenic aneurysm resection combined with splenectomy. The operation time of 28 patients was (124.3±55.1) min, the intraoperative blood loss was 100.0 (50.0, 162.5) ml, the postoperative hospital stay was (10.9±3.8) days, and the hospitalization cost was (3.7±1.2) wanyuan. Among the 28 patients, 5 cases (17.9%) developed pancreatic fistula, 1 case (3.6%) had partial splenic infarction, and 1 case (3.6%) had portal vein and splenic vein thrombosis after the operation.Conclusion:Laparoscopic surgery for splenic aneurysm is safe and feasible, with less surgical trauma and quick postoperative recovery.

Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P＜0.01).While Tb.Sp TS group was significantly higher than the CON group(P＜0.05),the maximum load and flexural strength of the femur significantly decreased(P＜0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P＜0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P＜0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P＜0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P＜0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.