Purpose: This study aimed to evaluate the long-term efficacy of the ligation of the intersphincteric fistula tract (LIFT) procedure in treating high transsphincteric fistulas. Methods: We conducted a retrospective study to evaluate the success rate of LIFT treatment in 82 patients with high transsphincteric fistulas involving at least one-third of the external sphincter. This study was carried out across 2 centers from November 2009 to February 2023. Results: All patients underwent successful surgery with a median operative time of 48.9 minutes (range, 20–80 minutes), and no intraoperative or postoperative complications were reported. The median follow-up duration was 85.5 months (range, 4–120 months), with 5 patients (6.1%) lost to follow-up. Treatment was successful in 62 patients, whose symptoms disappeared and both the external opening and the intersphincteric incision completely healed, yielding an overall efficiency rate of 80.5%. There were 15 cases (19.5%) of treatment failure, including 6 (7.8%) that converted to intersphincteric anal fistula and 9 (11.7%) that experienced persistent or recurrent fistulas. Only 1 patient reported minor overflow during the postoperative follow-up, but no other patients reported any significant discomfort. There were no statistically significant differences between patients with surgical success and those with treatment failure in terms of fistula length, history of previous abscess or anal fistula surgery, number of external orifices or fistulas, and location of fistulas (all P>0.05). Conclusion LIFT is a safe and effective sphincter-preserving procedure that yields satisfactory healing outcomes and has minimal impact on anal function.

Purpose: This study aimed to evaluate the long-term efficacy of the ligation of the intersphincteric fistula tract (LIFT) procedure in treating high transsphincteric fistulas. Methods: We conducted a retrospective study to evaluate the success rate of LIFT treatment in 82 patients with high transsphincteric fistulas involving at least one-third of the external sphincter. This study was carried out across 2 centers from November 2009 to February 2023. Results: All patients underwent successful surgery with a median operative time of 48.9 minutes (range, 20–80 minutes), and no intraoperative or postoperative complications were reported. The median follow-up duration was 85.5 months (range, 4–120 months), with 5 patients (6.1%) lost to follow-up. Treatment was successful in 62 patients, whose symptoms disappeared and both the external opening and the intersphincteric incision completely healed, yielding an overall efficiency rate of 80.5%. There were 15 cases (19.5%) of treatment failure, including 6 (7.8%) that converted to intersphincteric anal fistula and 9 (11.7%) that experienced persistent or recurrent fistulas. Only 1 patient reported minor overflow during the postoperative follow-up, but no other patients reported any significant discomfort. There were no statistically significant differences between patients with surgical success and those with treatment failure in terms of fistula length, history of previous abscess or anal fistula surgery, number of external orifices or fistulas, and location of fistulas (all P>0.05). Conclusion LIFT is a safe and effective sphincter-preserving procedure that yields satisfactory healing outcomes and has minimal impact on anal function.

Purpose: This study aimed to evaluate the long-term efficacy of the ligation of the intersphincteric fistula tract (LIFT) procedure in treating high transsphincteric fistulas. Methods: We conducted a retrospective study to evaluate the success rate of LIFT treatment in 82 patients with high transsphincteric fistulas involving at least one-third of the external sphincter. This study was carried out across 2 centers from November 2009 to February 2023. Results: All patients underwent successful surgery with a median operative time of 48.9 minutes (range, 20–80 minutes), and no intraoperative or postoperative complications were reported. The median follow-up duration was 85.5 months (range, 4–120 months), with 5 patients (6.1%) lost to follow-up. Treatment was successful in 62 patients, whose symptoms disappeared and both the external opening and the intersphincteric incision completely healed, yielding an overall efficiency rate of 80.5%. There were 15 cases (19.5%) of treatment failure, including 6 (7.8%) that converted to intersphincteric anal fistula and 9 (11.7%) that experienced persistent or recurrent fistulas. Only 1 patient reported minor overflow during the postoperative follow-up, but no other patients reported any significant discomfort. There were no statistically significant differences between patients with surgical success and those with treatment failure in terms of fistula length, history of previous abscess or anal fistula surgery, number of external orifices or fistulas, and location of fistulas (all P>0.05). Conclusion LIFT is a safe and effective sphincter-preserving procedure that yields satisfactory healing outcomes and has minimal impact on anal function.

Purpose: This study aimed to evaluate the long-term efficacy of the ligation of the intersphincteric fistula tract (LIFT) procedure in treating high transsphincteric fistulas. Methods: We conducted a retrospective study to evaluate the success rate of LIFT treatment in 82 patients with high transsphincteric fistulas involving at least one-third of the external sphincter. This study was carried out across 2 centers from November 2009 to February 2023. Results: All patients underwent successful surgery with a median operative time of 48.9 minutes (range, 20–80 minutes), and no intraoperative or postoperative complications were reported. The median follow-up duration was 85.5 months (range, 4–120 months), with 5 patients (6.1%) lost to follow-up. Treatment was successful in 62 patients, whose symptoms disappeared and both the external opening and the intersphincteric incision completely healed, yielding an overall efficiency rate of 80.5%. There were 15 cases (19.5%) of treatment failure, including 6 (7.8%) that converted to intersphincteric anal fistula and 9 (11.7%) that experienced persistent or recurrent fistulas. Only 1 patient reported minor overflow during the postoperative follow-up, but no other patients reported any significant discomfort. There were no statistically significant differences between patients with surgical success and those with treatment failure in terms of fistula length, history of previous abscess or anal fistula surgery, number of external orifices or fistulas, and location of fistulas (all P>0.05). Conclusion LIFT is a safe and effective sphincter-preserving procedure that yields satisfactory healing outcomes and has minimal impact on anal function.

Purpose: This study aimed to evaluate the long-term efficacy of the ligation of the intersphincteric fistula tract (LIFT) procedure in treating high transsphincteric fistulas. Methods: We conducted a retrospective study to evaluate the success rate of LIFT treatment in 82 patients with high transsphincteric fistulas involving at least one-third of the external sphincter. This study was carried out across 2 centers from November 2009 to February 2023. Results: All patients underwent successful surgery with a median operative time of 48.9 minutes (range, 20–80 minutes), and no intraoperative or postoperative complications were reported. The median follow-up duration was 85.5 months (range, 4–120 months), with 5 patients (6.1%) lost to follow-up. Treatment was successful in 62 patients, whose symptoms disappeared and both the external opening and the intersphincteric incision completely healed, yielding an overall efficiency rate of 80.5%. There were 15 cases (19.5%) of treatment failure, including 6 (7.8%) that converted to intersphincteric anal fistula and 9 (11.7%) that experienced persistent or recurrent fistulas. Only 1 patient reported minor overflow during the postoperative follow-up, but no other patients reported any significant discomfort. There were no statistically significant differences between patients with surgical success and those with treatment failure in terms of fistula length, history of previous abscess or anal fistula surgery, number of external orifices or fistulas, and location of fistulas (all P>0.05). Conclusion LIFT is a safe and effective sphincter-preserving procedure that yields satisfactory healing outcomes and has minimal impact on anal function.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective:To examine the prevention effecacy and safety of preprotein convertase subtilisin-kexin 9 (PCSK9) inhibitors in stroke in patients with atherosclerotic cardiovascular disease (ASCVD) at primary and secondary prevention.Methods:PubMed, Embase, Web of Science, Cochrane Library, and Wanfang and CNKI databases were searched for randomized controlled trials comparing evolocumab, alirocumab, tafolecimab or inclisiran (experimental group) with placebo or conventional therapy (control group) in hyperlipidemia and ASCVD from inception to March 2024. Valid data were extracted after screening and applying Cochrane Literature quality assessment tool to assess the literature quality. Efficacy outcome (incidences of stroke and ischemic stroke) and safety outcome (cardiovascular mortality, and incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke) were recorded. Meta analysis of the extracted data was conducted using Stata software to calculate the risk difference ( RD). Results:Twenty articles (21 randomized controlled trials) were included with 62 799 patients. For primary prevention, no significant difference was found between PCSK9 inhibitors and control groups in stroke incidence ( RD=0.000, 95% CI: -0.002-0.003, P=0.905) or ischemic stroke incidence ( RD=0.001, 95% CI: -0.005-0.006, P=0.824); incidence of creatine kinase increased by more than 3 times in the PCSK9 inhibitors group was significantly decreased compared with that in the control group ( RD=-0.005, 95% CI: -0.010-0.000, P=0.039). For secondary prevention, PCSK9 inhibitors group had significantly reduced stroke incidence ( RD=-0.004, 95% CI: -0.006--0.002, P<0.001) and ischemic stroke incidence ( RD=-0.003, 95% CI: -0.005--0.002, P<0.001) compared with control group; no significant differences in cardiovascular mortality, or incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke were noted between the PCSK9 inhibitors group and control group ( P>0.05). Conclusion:PCSK9 inhibitors in primary prevention have no significant effect on stroke or ischemic stroke incidences, but can decrease the incidence of creatine kinase increased by more than 3 times; PCSK9 inhibitors in secondary prevention can reduce stroke and ischemic stroke incidences without increasing complications and thus enjoying certain safety.

Objective:To observe the effects of preventative moxibustion on analgesia,substance P(SP),prostaglandin(PG)F2α and PGE2 in rats with dysmenorrhea due to cold-dampness stagnation,and to explore the analgesic mechanism. Methods:Sixty-four female Wistar non-pregnant rats were randomly divided into a blank group,a model group,a Western medicine group,and a preventative moxibustion group,with 16 rats in each group.Eight qualified diestrus rats were selected from each group.Except for the blank group,the other three groups established models of dysmenorrhea due to cold-dampness stagnation using an ice water bath combined with estradiol benzoate and oxytocin.On the 8th day after modeling,the preventative moxibustion group was treated with gentle moxibustion at Shenque(CV8)and Guanyuan(CV4),and the Western medicine group was given ibuprofen solution for 4 consecutive days.On the 11th day,the intervention groups(i.e.the Western medicine group and the preventative moxibustion group)were treated once again after being injected with oxytocin.The writhing score and the pain threshold of rats were determined;the serum levels of brain-derived neurotrophic factor(BDNF),SP,PGF2α,and PGE2 were measured;the mRNA and protein expression levels of BDNF and its receptor tropomyosin receptor kinase B(TrkB)in the spinal dorsal horn and hypothalamus were detected. Results:Compared with the blank group,the writhing score increased(P<0.01),the pain threshold decreased(P<0.01),the serum levels of BDNF,SP,and PGF2α increased(P<0.01),while the PGE2 decreased(P<0.01);the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus increased(P<0.01)in the model group.Compared with the model group,the writhing score decreased,the pain threshold increased,the serum BDNF,SP,and PGF2α levels decreased significantly,the serum PGE2 level increased,and the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus decreased significantly in the preventative moxibustion group and the Western medicine group,while the inter-group differences were significant(P<0.01).Compared with the Western medicine group,the writhing score decreased,the pain threshold increased,the serum BDNF,SP,and PGF2α,levels decreased,the serum PGE2 level increased,and the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus in the preventative moxibustion group decreased significantly,while the inter-group differences were significant(P<0.05 or P<0.01). Conclusion:Preventative moxibustion at Shenque(CV8)and Guanyuan(CV4)can improve the pain sensitization state of rats with dysmenorrhea due to cold-dampness stagnation,down-regulate the mRNA and protein expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus;regulation of the serum SP,PGF2α,and PGE2 levels may be part of the mechanism.

Objective To explore the mechanism of the treatment of primary dysmenorrhea(PD)by mild moxibustion on"Shenque"and"Guanyuan"acupoints based on the regulation of cAMP-PKA signaling pathway on TRPV1.Methods Totally 32 female non-pregnant Wistar rats were randomly divided into blank group,model group,mild moxibustion group and capsazepine group,with 8 rats in each group.Except for the blank group,the other groups all used estradiol benzoate intraperitoneal injection combined with ice water bath to establish a PD cold-dampness stagnation syndrome rat model.Intervention began on the first day of modeling,the mild moxibustion group selects"Shenque"and"Guanyuan"for mild moxibustion,20 min per time,the capsazepine group was injected capsazepine 2 mg/kg,once a day for 10 consecutive days.ELISA was used to detect uterine PGF2α and cAMP content,immunofluorescence staining was used to detect TRPV1 expression in uterine tissue,Western blot was used to detect PKA,p-PKA and TRPV1 protein expression.Results Compared with the blank group,the latency period of body twisting in the model group rats decreased,and the body twisting score increased(P<0.01);the contents of PGF2α and cAMP in uterine tissue increased(P<0.01),and the expressions of TRPV1 and p-PKA proteins increased(P<0.01).Compared with the model group,the mild moxibustion group and capsazepine group showed an increase in the latency period of body twisting and a decrease in the body twisting score(P<0.01);the content of PGF2α and cAMP in uterine tissue decreased(P<0.01),and the expressions of TRPV1 and p-PKA proteins decreased(P<0.05,P<0.01).Compared with the mild moxibustion group,the capsazepine group showed an increase in the latency period of body twisting and a decrease in the body twisting score(P<0.01);the contents of PGF2α and cAMP in uterine tissue decreased(P<0.05,P<0.01),and the expressions of TRPV1 protein decreased(P<0.05).Conclusion Mild moxibustion at"Shenque"and"Guanyuan"acupoints has obvious analgesic effect on PD rats,and its mechanism may be related to the regulation of uterine cAMP-PKA signaling pathway mediated TRPV1 protein expression.