Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

ObjectiveTo compare the effects of different tidal volumes and positive end expiratory pressures （PEEPs） during mechanical ventilation on the cardiac output of pigs measured by pulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis， and to explore their consistency in cardiac output determination. MethodsTwelve experimental pigs were selected and randomly divided into 3 groups， with 4 pigs in each. Cardiac output was measured by different methods， control group by pulmonary artery catheter， group A by transpulmonary thermodilution and group B by pulse contour analysis. Then we compared the effects of different tidal volumes and PEEPs on the cardiac output of pigs and to explore the consistency. The correlation coefficient between pulse contour analysis and pulmonary artery catheter was r=0.754， and they were positively correlated. The correlation coefficient between transpulmonary thermodilution and pulmonary artery catheter was r=0.771， and they were positively correlated. In determining cardiac output， pulse contour analysis was consistent with pulmonary artery catheter， with a relative error of 13.5% between them； transpulmonary thermodilution was consistent with pulmonary artery catheter， with a relative error of 12.9% between them. The cardiac output decreased significantly along with the increase of tidal volumes or PEEPs and the differences were statistically significant （P<0.05） ConclusionPulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis are well consistent with each other in measuring the cardiac output of pigs. The pigs’cardiac output gradually decreased along with the increase of tidal volumes or PEEPs during mechanical ventilation.

AIM: To explore the clinical efficacy of the myopic with moderate to high astigmatism correction between corneal topography-guided femtosecond laser in situ keratomileusis(FS-LAISK)and Toric implantable collamer lens(TICL).METHODS: A total of 60 patients(115 eyes)with moderate to high astigmatism in myopia(115 eyes)from June 2019 to June 2021 and treated in the refractive center of Heyuan Aier Eye Hospital were enrolled in the study, then were divided into Group A and Group B according to the operations they would accept. There were 32 patients(62 eyes)in the Group A treated with corneal topography-guided FS-LASIK and 28 patients(53 eyes)in the Group B treated with TICL implantation. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical diopter and residual astigmatism were recorded preoperatively and postoperatively at 3mo, surgical safety and efficacy were evaluated, and the Alpins vector analysis was used to evaluate the astigmatism.RESULTS: The postoperative at 3mo, there were no differences in the safety index(1.163±0.167 vs 1.136±0.194)and the efficacy index(1.145±0.159 vs 1.123±0.196)between the patients of the two groups(P>0.05). However, the astigmatism vector analysis showed that there were statistically differences in the index of success index [0.125(0.091, 0.200)vs 0.200(0.167, 0.250)], the correction index [1.000(0.902, 1.066)vs 0.834(0.783, 0.869)] and the flattening index [1.000(0.922, 1.079)vs 0.835(0.795, 0.870)](P<0.01).CONCLUSION:Corneal topography-guided FS-LASIK and TICL implantation were effective and safe in correcting myopia with moderate to high astigmatism, and corneal topography-guided FS-LASIK perform better than TICL implantation for the astigmatism correction.

Objective:To Investigate comprehensive predictive ability of first-trimester complete blood count combined with maternal characteristics for gestational diabetes mellitus (GDM).Methods:From May 2015 to July 2018, 1 412 pregnant women were retrospectively screened at the Fifth People′s Hospital of Shanghai, Fudan University. We recruited 258 women who developed GDM and 1 154 women who had normal glucose level during pregnancy. At the first visit, clinical data and complete blood count result were obtained. GDM prediction models were established through logistic regression analysis of GDM related risk factors and the prediction abilities of each model were compared.Results:Logistic regression analyses identified age, pre-pregnancy body mass index, previous GDM history, family history of diabetes mellitus, the neutrophil-to-lymphocyte ratio, leukocyte, neutrophil, and monocyte counts were significantly independent predictors of GDM. In the entire cohort, the predictive ability of neutrophil and monocyte counts together with maternal basal characteristics model for the development of GDM [areas under the receiver operating characteristic curve (AUC-ROC)=0.809, integrated discrimination improvement (IDI)=0.056, P=0.001] was the best among various models (basal characteristics model, AUC-ROC=0.753; Monocyte count+ basal characteristics model, AUC-ROC=0.764; neutrophil count + basal characteristics model, AUC-ROC=0.775). Similar results obtained by the same way in all pregnant women without previous GDM history. Conclusion:It could improve the prediction of GDM with model incorporated maternal characteristics and first-trimester neutrophil and monocyte counts.

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. This compound attenuated glioma cell migration, glioma cell invasion, and angiogenesis. Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau, disrupted microtubule dynamics, and induced a G2/M phase cell cycle arrest. In an glioma model, PCC0208017 showed robust anti-tumor activity, blood-brain barrier permeability, and a good oral pharmacokinetic profile. Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4. Taken together, our study describes for the first time that PCC0208017, a novel MARK3/MARK4 inhibitor, might be a promising lead compound for treatment of glioma.

Objective To investigate the threshold values of insulin resistance ( IR) assessed by homeostasis model and the prevalence of IR in elderly people over 60 years old in Minhang district of Shanghai, and to evaluate the relationship between IR and metabolic syndrome ( MS) . Methods A total of 3003 elderly people aged 60 and over in the Jiangchuan community of Minhang District, Shanghai, were recruited, including 1286 males and 1717 females. Blood pressure, waist circumference, BMI, blood routine, serum creatinine, blood lipids, glucose, and fasting insulin were measured in all populations studied. Homeostasis model assessment ( HOMA) was used to estimate IR, and MS, and defined according to three diagnostic criteria including NCEP-ATPIII, IDF, and CDS. Results 75th percentile, 80th percentile and 90th percentile of HOMA values in 268 subjects with normotensive and normal BMI, glucose tolerance were considered as the thresholds of IR. The cut-off values were 2. 78, 3. 01 and 3. 56, respectively. And the prevalence of IR were 50. 0％, 42. 1％, and 27. 2％, respectively. IR level was significantly higher in people with MS. Based on the receiver operating characteristic ( ROC ) curve analysis, HOMA-IR and QUICKI index predicted MS well, and the optimal thresholds for diagnosing MS of HOMA-IR were 3. 17 for NCEP-ATPⅢ, 3. 02 for IDF and 3. 03 for CDS. BMI was the best factor for diagnosing IR among different MS components. Logistic regression analysis showed that gender, WC, BMI, SBP, HDL-C, TG, FBG and WBC were independent risk factors for IR. FBG≥5.84 mmol/L was the most dangerous factor of IR (OR=3.603,P<0.01), followed by WC≥85.4 cm(OR=2.152, P<0.01) and BMI≥24.6 kg/m2(OR=2.150,P<0.01). Conclusion The cut-off values of IR estimated by HOMA and the prevalence of IR were higher in elder subjects than other populations. IR was significantly positively correlated with MS. Excluding the conditions that insulin measurement were affected by external factors, HOMA-IR may predict the risk of MS. The components of MS were relative specific measurements of IR, FBG, BMI and WC were important risk predictors of IR in the elderly.

BACKGROUND: Adipose-derived stem cells have the advantages of easy access, easy separation, small trauma, and rapid proliferation. Current treatments for kidney injury are more limited, and adipose-derived stem cells may provide a new treatment route. OBJECTIVE: To investigate the effects of adipose-derived stem cell transplantation on the kidney function of rats with acute kidney injury induced by crush injury in rats. METHODS: Cryopreserved adipose-derived stem cells were recovered in vitro and cultured to prepare cell suspension following labeling with PKH-26. Twenty rats were randomly selected from 66 experimental Sprague-Dawley rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.) as normal control group. In the 40 of the remaining 46 rats, a pathological model of acute kidney injury caused by compression injury was successfully established by the use of forceps to double the proximal hind limbs. The 40 rat models were divided into model group and cell transplantation group, with 20 rats in each group. After 6 hours of modeling, the rats in the model group were given intravenous injection of normal saline (20 μL) , and the rats in the cell group were given intravenous injection of PKH-26-labeled adipose-derived stem cells (20 μL, 3×106/L) , once a day for 3 continuous days. The levels of serum creatinine and urea nitrogen were measured in each group at 1, 3, 14 and 21 days after transplantation. The left kidney of the rats in each group was observed using hematoxylin-eosin staining, TUNEL staining, RT-PCR and western blot assay at 3 and 21 days after cell transplantation. RESULTS AND CONCLUSION: (1) The levels of creatinine and urea nitrogen in the serum of rats at 1, 3, 14 and 21 days after cell transplantation were significantly higher in the model group than the normal control group (P < 0.05) and cell transplantation group (P < 0.05). (2) At 3 and 21 days after cell transplantation, the scores on the kidney injury and apoptotic rate of kidney cells were ranked as follows: model group> cell transplantation group> normal control group, and there were significant differences between groups (P < 0.05). (3) At 3 and 21 days after cell transplantation, the expressions of bax and Caspase-3 in the kidney tissue at mRNA and protein levels were significantly higher in the model group and cell transplantation than the normal control group (P < 0.01) as well as significantly higher in the cell transplantation group than the model group (P < 0.05). To conclude, adipose-derived stem cell transplantation has obvious repairing effect on acute kidney injury caused by crush injury, and its mechanism may be related to the involvement of adipose-derived stem cells in regulating the expression of bax and Caspase-3.

Objective To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People′s Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m2, (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m2, (6.7±1.6) mmol/L, (6.1± 1.2) mmol/L; (22±3) kg/m2, (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM ( OR=2.799, 95% CI :1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.

Objective: To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods: A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People's Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results: (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m², (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m², (6.7±1.6) mmol/L, (6.1±1.2) mmol/L; (22±3) kg/m², (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM (OR=2.799, 95%CI: 1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.