1.Laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis versus laparoscopic total colectomy with ileorectal anastomosis for slow transit constipation: a multicenter retrospective cohort study
Yang LUO ; Taotao HOU ; Yifei MU ; Chundi MIAO ; Tingyue GONG ; Jun QIN ; Dongyang WANG ; Dawei SONG ; Hao LI ; Shaolan QIN ; Rong CUI ; Tingfeng WANG ; Ming ZHONG ; Minhao YU
Chinese Journal of Gastrointestinal Surgery 2025;28(12):1426-1433
Objective:To compare postoperative anal function recovery between laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis for slow transit constipation.Methods:This multicenter retrospective cohort study enrolled patients meeting the following criteria: (1) severe constipation symptoms (<2 bowel movements/week), absent or insignificant defecation urge, abdominal distension, requiring laxatives to maintain bowel movements or laxatives being ineffective; (2) constipation symptoms for over 5 years, ineffective after >2 years of medical treatment, with strong desire for surgery; (3) significantly prolonged colon transit time (>72 hours) without significant gastric or small intestinal transit dysfunction; (4) no organic colonic lesions confirmed by colonoscopy and abdominal CT. Exclusion criteria: (1) patients undergoing open surgery; (2) exclusion of outlet obstruction constipation (e.g., rectocele, rectal prolapse, puborectalis spasm) by functional defecation MRI; (3) comorbid psychiatric disorders; (4) missing clinical data or loss to follow-up (postoperative follow-up <24 months). Based on these criteria, clinical and follow-up data were collected from 220 patients who underwent either laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis (LSC group, n = 115) or laparoscopic total colectomy with ileorectal anastomosis (LTC group, n = 105) for slow transit constipation between January 2013 and December 2022. Subjective anal function (Constipation Severity Score and Wexner Fecal Incontinence Score) and objective anal function (positive rate of rectoanal inhibitory reflex [RAIR] and anorectal manometry) were observed preoperatively and at 6, 12, and 24 months postoperatively. Results:No significant differences were found in baseline characteristics between the two groups (all P >0.05). All surgeries were completed successfully without major significant complications. Subjective anal function assessment: At 24 months postoperatively, Constipation Severity Scores decreased significantly compared to preoperative scores in both groups [LSC group: (25.2±2.8) vs. (2.9±1.8), P <0.001; LTC group: (25.8±2.9) vs. (2.8±1.9), P<0.001]. No significant differences were found between the groups at 6, 12, and 24 months postoperatively (all P>0.05). Wexner Fecal Incontinence Scores at 24 months were significantly lower than those at 6 months in both groups [LSC group: (12.9±1.8) vs. (3.9±2.5), P<0.001; LTC group: (12.6±1.8) vs. (5.4±2.4), P<0.001]. Although no significant difference was found at 6 months ( P = 0.190), the LSC group had significantly lower Wexner scores than the LTC group at 12 and 24 months postoperatively (both P < 0.001). Objective anal function assessment: (1) Positive RAIR rate: Preoperative positive RAIR rates were 33.0% (38/115) in the LSC group and 25.7% (27/105) in the LTC group ( P > 0.05). At 24 months, positive rates increased significantly in both groups [LSC: 66.1% (76/115); LTC: 63.8% (67/105)] compared to preoperative rates (both P<0.001), but no significant differences were found between groups at 6, 12, and 24 months (all P>0.05). (2) Resting pressure (RP) and squeeze pressure (SP): No significant differences were found in preoperative RP and SP between groups (all P>0.05). The LSC group had significantly higher RP and SP than the LTC group at 6 and 12 months postoperatively (all P<0.05), but no significant differences were found at 24 months ( P>0.05). Conclusion:Both laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis are safe for patients with slow transit constipation. However, laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis offers superior postoperative anal function recovery.
2.Analysis of Clinical Features and Multi-Slice Spiral CT Image Features of Acute Appendicitis in Soldiers Who Have Been Living in Plateau for A Long Time
Li-na YUE ; Juan-qin NIU ; Gang CHEN ; Man-ping CHENG ; Ning-xia MU ; Jia FAN ; Kang LIU ; Yu-lan NIU ; Ya-ping HE ; Zhong-hua LI
Progress in Modern Biomedicine 2025;25(11):1869-1878
Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14%),lower ileum 10 cases(17.86%),posterior cecum 16 cases(28.57%),lower cecum 9 cases(16.07%),lateral cecum 2 cases(3.58%),posterior ileum 6 cases(10.71%),high(subhepatic)9 cases(16.07%),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter>6 mm in 49 cases(87.50%),appendicular wall thickening>2 mm in 42 cases(75.00%),ppendiceal dilation lumen and effusion in 29 cases(51.79%),appendix indistinctness in 3 cases(5.36%),lppendix fecalith:27 cases(48.21%),gas in the appendix in 16 cases(28.57%).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14%),appendiceal cellulitis with peripheral abscess in 9 cases(16.07%),peritonitis and ascites in 13 cases(23.21%),ileocecal intestinal wall thickening in 22 cases(39.29%),mesenteric lymph node enlargement in 16 cases(28.57%),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93%).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.
3.Mechanism study on the improvement of lung injury in mice with in-fluenza A virus pneumonia by Shufeng Jiedu capsules based on regu-lating intestinal microflora
Yikun WU ; Hongmin GUO ; Yan LI ; Weige MU ; Shuyun HUANG ; Jiuling ZHU ; Zhu YANG ; Shuzhi ZHONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1351-1360
AIM:To study the improvement effect and possible mechanism of Shufeng Jiedu capsules(SFJDC)on viral pneumonia.METHODS:Forty-eight BALB/c mice were used to establish a viral pneumo-nia model by intranasal administration of influenza A virus H1N1.They were randomly divided into 4 groups,with twelve mice in each group.Except for the Model group,the treatment group was given oseltamivir(OSTW),low and high dose groups of Shufeng Jiedu capsules(SFJDC-L,SFJD-H)by gavage,take another 12 mice as the normal group,continu-ously administered for 7 days.The physical signs of each group of mice were observed during the ad-ministration process,and the daily body weight change rate and disease activity index was calculat-ed;After administration,lung,intestinal tissue,and intestinal contents were taken,and the pathological changes in mouse lung tissue were detected using hematoxylin eosin(HE)staining method,Alisin blue staining was used to detect goblet cells in the intes-tinal wall;RT-qPCR method for detecting viral load influenza(infA)and the expression of tumor necro-sis factor-a(TNF-α)and interleukin-6(IL-6)mRNA in mouse lung tissue;Detection of mouse gut mi-crobiota using 16S rRNA high-throughput sequenc-ing;ELISA method for detecting lipopolysaccharide(LPS),TNF-α and IL-6 level in mouse serum;The ex-pression of cyclic GMP AMP synthase(cGAS),inter-feron gene stimulating protein(STING),phospho-STING(p-STING),nuclear factor-κB(NF-κB)phos-pho-nuclear factor-κB(p-NF-κB)in lung tissue and ZO-1,Occludin in small small intestine was detected by Western Blotting.RESULTS:Compared with the model group,the lung index and viral load of mice in the Shufeng Jiedu capsules group were signifi-cantly reduced(P<0.01);significant reduction in lung tissue inflammation accompanied by TNF-α;The expression level of IL-6 mRNA decreased(P<0.01);The abundance of Firmicutes and Lachnospi-raceae in the intestine significantly increased(P<0.01),while the abundance of Bacteroidetes and Bacteroidaceae communities significantly de-creased(P<0.05 or 0.01);The number of goblet cells in the small intestine epithelium significantly increased(P<0.01);the levels of serum LPS and TNF-α,IL-6 were significantly reduced(P<0.01);The protein expression level of cGAS,p-STING,p-NF-κB significantly decreased in lung tissue(P<0.05 or 0.01),ZO-1,Occludin significantly decreased in small intestine(P<0.05).CONCLUSION:Shufeng Jie-du capsules reduces the inflammatory response of mice lung tissue,and its mechanism may be relat-ed to its regulation of intestinal flora,protection of intestinal mucosal barrier,and reduction the activa-tion of cGAS/STING/NF-κB signaling pathway ac-tived by LPS leakaging from the intestine.
4.Exploration of basket trial design with Bayesian method and its application value in traditional Chinese medicine.
Si-Cun WANG ; Mu-Zhi LI ; Hai-Xia DANG ; Hao GU ; Jun LIU ; Zhong WANG ; Ya-Nan YU
China Journal of Chinese Materia Medica 2025;50(3):846-852
Basket trial, as an innovative clinical trial design concept, marks the transformation of medical research from the traditional large-scale and single-disease treatment to the precise and individualized treatment. By gradually incorporating the Bayesian method during development, the trial design becomes more scientific and reasonable and increases its efficiency. The fundamental principle of the Bayesian method is the utilization of prior knowledge in conjunction with new observational data to dynamically update the posterior probability. This flexibility enhances the basket trial's capacity to effectively adapt to variations during the research process. Consequently, it enables researchers to dynamically adjust research strategies based on accumulated data and improve the predictive accuracy regarding treatment responses. In addition, the design concept of the basket trial aligns with the traditional Chinese medicine(TCM) principle of "homotherapy for heteropathy". The principle of "homotherapy for heteropathy" emphasizes that under certain conditions, different diseases may have the same treatment. Similarly, basket trials allow using a uniform trial design across multiple diseases, offering enhanced operational and significant practical value in the realm of TCM, particularly within the context of syndrome-based disease research. By introducing basket trials, the design of TCM clinical studies will be more scientific and yield higher-quality evidence. This study systematically categorized various Bayesian methods and models utilized in basket trials, evaluated their strengths and weaknesses, and identified their appropriate application contexts, so as to offer a practical guide for designing basket trials in the realm of TCM.
Bayes Theorem
;
Humans
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Medicine, Chinese Traditional/methods*
;
Research Design
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Clinical Trials as Topic/methods*
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Drugs, Chinese Herbal/therapeutic use*
5.Effect of High-Altitude Hypoxia on the Pharmacokinetics and Brain Distribution of Phenytoin Sodium in Epileptic Rats
Xiaojing ZHANG ; Yan ZHONG ; Hongfang MU ; Wenbin LI ; Xiaomin YANG ; Rong WANG
Journal of Sichuan University (Medical Sciences) 2025;56(3):825-830
Objective To investigate the effects of high-altitude hypoxic environment on the pharmacokinetic characteristics and brain tissue distribution of phenytoin sodium in epileptic rats.Methods A total of 70 male SPF-grade Wistar rats aged 2 months and weighing(200±20)g were used in the study.An epilepsy model was induced in the rats using the lithium chloride-pilocarpine method.The successfully modeled rats were randomly assigned to a normoxic treatment group and a high-altitude hypoxic treatment group.Phenytoin sodium was administered via intragastric gavage at a dose of 50 mg/kg in both groups.Blood samples were collected from the orbital venous plexus before treatment and 0.5,1,2,3,4,6,8,10,and 24 h post treatment.The animals were euthanized after the final blood collection,and samples of the liver and the whole brain tissue were collected.In the brain tissue distribution experiment,brain tissue samples were collected at 0.5,1,2,and 4 h after drug administration.The concentration of phenytoin sodium in rat plasma and brain tissue was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters were calculated using WinNolin 8.1 software.The expression levels of CYP2C9 in liver tissue and those of P-gp in brain tissue of epileptic rats were determined by Western blot.Results Compared with those in the normoxia group,the peak concentration,peak time,and half-life of phenytoin sodium in the high-altitude hypoxia group were significantly decreased by 46.0%,42.3%,and 55.5%,respectively(all P<0.05);the clearance rate was significantly increased by 162.0%(P<0.05);and the area under the curve of plasma concentration-time curve was decreased by 45.6%(P<0.01).At 0.5,1,and 2 hours after administration,compared with that in the normoxia treatment group,the concentration of phenytoin sodium in the brain tissue of the high-altitude hypoxia treatment group was significantly decreased by 78.1%,63.5%,and 32.5%,respectively(all P<0.05).Western blot results showed that the expression levels of CYP2C9 in the liver tissue and P-gp in the brain tissue of rats in the high-altitude hypoxia group were approximately 1.78 and 1.65 times higher than those in the normoxia group,respectively(both P<0.05).Conclusion The hypoxic environment at high altitudes can promote the metabolism of phenytoin sodium,reduce its absorption efficiency,and change the characteristics its distribution in the brain,which may be related to the up-regulation of the expression of CYP2C9 in the liver and that of P-gp in the brain.
6.Mechanism of senegenin in improving lipopolysacchride-induced inflammatory response of BV2 microglial cell
Bing-Tao MU ; Min-Fang GUO ; Jing-Wen YU ; Jia-Lei CAO ; Feng-Jun YANG ; Si-Wei JIA ; Qing SU ; Tao MENG ; Cun-Gen MA ; Jie-Zhong YU ; Li-Juan SONG
Medical Journal of Chinese People's Liberation Army 2025;50(2):188-196
Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2~20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.
7.Mechanism study on the improvement of lung injury in mice with in-fluenza A virus pneumonia by Shufeng Jiedu capsules based on regu-lating intestinal microflora
Yikun WU ; Hongmin GUO ; Yan LI ; Weige MU ; Shuyun HUANG ; Jiuling ZHU ; Zhu YANG ; Shuzhi ZHONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1351-1360
AIM:To study the improvement effect and possible mechanism of Shufeng Jiedu capsules(SFJDC)on viral pneumonia.METHODS:Forty-eight BALB/c mice were used to establish a viral pneumo-nia model by intranasal administration of influenza A virus H1N1.They were randomly divided into 4 groups,with twelve mice in each group.Except for the Model group,the treatment group was given oseltamivir(OSTW),low and high dose groups of Shufeng Jiedu capsules(SFJDC-L,SFJD-H)by gavage,take another 12 mice as the normal group,continu-ously administered for 7 days.The physical signs of each group of mice were observed during the ad-ministration process,and the daily body weight change rate and disease activity index was calculat-ed;After administration,lung,intestinal tissue,and intestinal contents were taken,and the pathological changes in mouse lung tissue were detected using hematoxylin eosin(HE)staining method,Alisin blue staining was used to detect goblet cells in the intes-tinal wall;RT-qPCR method for detecting viral load influenza(infA)and the expression of tumor necro-sis factor-a(TNF-α)and interleukin-6(IL-6)mRNA in mouse lung tissue;Detection of mouse gut mi-crobiota using 16S rRNA high-throughput sequenc-ing;ELISA method for detecting lipopolysaccharide(LPS),TNF-α and IL-6 level in mouse serum;The ex-pression of cyclic GMP AMP synthase(cGAS),inter-feron gene stimulating protein(STING),phospho-STING(p-STING),nuclear factor-κB(NF-κB)phos-pho-nuclear factor-κB(p-NF-κB)in lung tissue and ZO-1,Occludin in small small intestine was detected by Western Blotting.RESULTS:Compared with the model group,the lung index and viral load of mice in the Shufeng Jiedu capsules group were signifi-cantly reduced(P<0.01);significant reduction in lung tissue inflammation accompanied by TNF-α;The expression level of IL-6 mRNA decreased(P<0.01);The abundance of Firmicutes and Lachnospi-raceae in the intestine significantly increased(P<0.01),while the abundance of Bacteroidetes and Bacteroidaceae communities significantly de-creased(P<0.05 or 0.01);The number of goblet cells in the small intestine epithelium significantly increased(P<0.01);the levels of serum LPS and TNF-α,IL-6 were significantly reduced(P<0.01);The protein expression level of cGAS,p-STING,p-NF-κB significantly decreased in lung tissue(P<0.05 or 0.01),ZO-1,Occludin significantly decreased in small intestine(P<0.05).CONCLUSION:Shufeng Jie-du capsules reduces the inflammatory response of mice lung tissue,and its mechanism may be relat-ed to its regulation of intestinal flora,protection of intestinal mucosal barrier,and reduction the activa-tion of cGAS/STING/NF-κB signaling pathway ac-tived by LPS leakaging from the intestine.
8.Analysis of Clinical Features and Multi-Slice Spiral CT Image Features of Acute Appendicitis in Soldiers Who Have Been Living in Plateau for A Long Time
Li-na YUE ; Juan-qin NIU ; Gang CHEN ; Man-ping CHENG ; Ning-xia MU ; Jia FAN ; Kang LIU ; Yu-lan NIU ; Ya-ping HE ; Zhong-hua LI
Progress in Modern Biomedicine 2025;25(11):1869-1878
Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14%),lower ileum 10 cases(17.86%),posterior cecum 16 cases(28.57%),lower cecum 9 cases(16.07%),lateral cecum 2 cases(3.58%),posterior ileum 6 cases(10.71%),high(subhepatic)9 cases(16.07%),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter>6 mm in 49 cases(87.50%),appendicular wall thickening>2 mm in 42 cases(75.00%),ppendiceal dilation lumen and effusion in 29 cases(51.79%),appendix indistinctness in 3 cases(5.36%),lppendix fecalith:27 cases(48.21%),gas in the appendix in 16 cases(28.57%).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14%),appendiceal cellulitis with peripheral abscess in 9 cases(16.07%),peritonitis and ascites in 13 cases(23.21%),ileocecal intestinal wall thickening in 22 cases(39.29%),mesenteric lymph node enlargement in 16 cases(28.57%),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93%).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.
9.Laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis versus laparoscopic total colectomy with ileorectal anastomosis for slow transit constipation: a multicenter retrospective cohort study
Yang LUO ; Taotao HOU ; Yifei MU ; Chundi MIAO ; Tingyue GONG ; Jun QIN ; Dongyang WANG ; Dawei SONG ; Hao LI ; Shaolan QIN ; Rong CUI ; Tingfeng WANG ; Ming ZHONG ; Minhao YU
Chinese Journal of Gastrointestinal Surgery 2025;28(12):1426-1433
Objective:To compare postoperative anal function recovery between laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis for slow transit constipation.Methods:This multicenter retrospective cohort study enrolled patients meeting the following criteria: (1) severe constipation symptoms (<2 bowel movements/week), absent or insignificant defecation urge, abdominal distension, requiring laxatives to maintain bowel movements or laxatives being ineffective; (2) constipation symptoms for over 5 years, ineffective after >2 years of medical treatment, with strong desire for surgery; (3) significantly prolonged colon transit time (>72 hours) without significant gastric or small intestinal transit dysfunction; (4) no organic colonic lesions confirmed by colonoscopy and abdominal CT. Exclusion criteria: (1) patients undergoing open surgery; (2) exclusion of outlet obstruction constipation (e.g., rectocele, rectal prolapse, puborectalis spasm) by functional defecation MRI; (3) comorbid psychiatric disorders; (4) missing clinical data or loss to follow-up (postoperative follow-up <24 months). Based on these criteria, clinical and follow-up data were collected from 220 patients who underwent either laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis (LSC group, n = 115) or laparoscopic total colectomy with ileorectal anastomosis (LTC group, n = 105) for slow transit constipation between January 2013 and December 2022. Subjective anal function (Constipation Severity Score and Wexner Fecal Incontinence Score) and objective anal function (positive rate of rectoanal inhibitory reflex [RAIR] and anorectal manometry) were observed preoperatively and at 6, 12, and 24 months postoperatively. Results:No significant differences were found in baseline characteristics between the two groups (all P >0.05). All surgeries were completed successfully without major significant complications. Subjective anal function assessment: At 24 months postoperatively, Constipation Severity Scores decreased significantly compared to preoperative scores in both groups [LSC group: (25.2±2.8) vs. (2.9±1.8), P <0.001; LTC group: (25.8±2.9) vs. (2.8±1.9), P<0.001]. No significant differences were found between the groups at 6, 12, and 24 months postoperatively (all P>0.05). Wexner Fecal Incontinence Scores at 24 months were significantly lower than those at 6 months in both groups [LSC group: (12.9±1.8) vs. (3.9±2.5), P<0.001; LTC group: (12.6±1.8) vs. (5.4±2.4), P<0.001]. Although no significant difference was found at 6 months ( P = 0.190), the LSC group had significantly lower Wexner scores than the LTC group at 12 and 24 months postoperatively (both P < 0.001). Objective anal function assessment: (1) Positive RAIR rate: Preoperative positive RAIR rates were 33.0% (38/115) in the LSC group and 25.7% (27/105) in the LTC group ( P > 0.05). At 24 months, positive rates increased significantly in both groups [LSC: 66.1% (76/115); LTC: 63.8% (67/105)] compared to preoperative rates (both P<0.001), but no significant differences were found between groups at 6, 12, and 24 months (all P>0.05). (2) Resting pressure (RP) and squeeze pressure (SP): No significant differences were found in preoperative RP and SP between groups (all P>0.05). The LSC group had significantly higher RP and SP than the LTC group at 6 and 12 months postoperatively (all P<0.05), but no significant differences were found at 24 months ( P>0.05). Conclusion:Both laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis are safe for patients with slow transit constipation. However, laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis offers superior postoperative anal function recovery.
10.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

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