Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ²=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ²=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ²=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ²=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ²=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.
Humans ; Pelvic Exenteration/methods* ; Retrospective Studies ; Treatment Outcome ; Blood Loss, Surgical ; Laparoscopy/methods* ; Rectal Neoplasms/surgery*

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P>0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P<0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P<0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P<0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P=0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P=0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes (P<0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P=0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P=0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P<0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.
Dissection ; Humans ; Lymph Node Excision ; Lymph Nodes ; Prognosis ; Rectal Neoplasms/surgery* ; Treatment Outcome

OBJECTIVETo study the combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases (IMD).

METHODSA total of 3 381 samples ruled out of IMD by follow-up were randomly selected from 38 931 newborns who participated in the neonatal IMD screening during 2014-2016. The 3 381 neonates were categorized into seven groups according to their gestational age and birth weight: extremely preterm appropriate-for-gestational age (AGA) group (n=12), preterm small-for-gestational age (SGA) group (n=18), preterm AGA group (n=219), preterm large-for-gestational age (LGA) group (n=18), full-term SGA group (n=206), full-term AGA group (n=2 677), and full-term LGA group (n=231). Heel blood samples were collected from each group on postnatal days 3-7 after adequate breastfeeding. Levels of 17 key IMD-related metabolic indices in dried blood spots were measured using tandem mass spectrometry. Spearman′s correlation analysis was used to investigate the relationships between 17 IMD-related metabolic indices and their influencing factors, while covariance analysis was used to compare the metabolic indices between these groups.

RESULTSAfter adjusting the influencing factors such as physiological and pathological status, compared with the full-term AGA group, the extremely preterm AGA, preterm SGA, and preterm AGA groups had significantly reduced levels of leucine\isoleucine\hydroxyproline and valine (P<0.05); the preterm AGA group had a significantly decreased ornithine level (P<0.05); the extremely preterm AGA and preterm AGA groups had a significantly reduced proline level (P<0.05). Besides, the phenylalanine level in the extremely preterm AGA and preterm AGA groups, the methionine level in the preterm SGA group, and the tyrosine level in the preterm AGA group all significantly increased (P<0.05). The increased levels of free carnitine, acetylcarnitine, and propionylcarnitine were found in the preterm SGA and preterm AGA groups. The oleylcarnitine level also significantly increased in the preterm SGA group (P<0.05). Most carnitine indices showed significant differences between the SGA group and the AGA/LGA group in both preterm and full-term infants (P<0.05).

CONCLUSIONSLow gestational age and low birth weight may result in abnormal results in IMD screening. Therefore, gestational age and birth weight should be considered to comprehensively judge the abnormal results in IMD screening.

Birth Weight ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Small for Gestational Age ; Male ; Metabolic Diseases ; metabolism

Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91^phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91^phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.

Objective:To preliminarily verify the cross talk between tissue factor/active coagulation factor Ⅶ (TF/FⅦa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture.Methods:FⅦa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/F Ⅶa pathway,qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG),ligands of EGFR on mRNA and protein levels,respectively.After knocking down expression of TF by TF-targeted siRNA transfection,FⅦa was treated and mRNA expressions of AREG and EREG were detected to see whether the FⅦa-induced effects were dependent on TF.Expressions of mRNA of TF and FⅦwere detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells.Results:After TF/FⅦa pathway was activated,for HT-29 cells,expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group,gene expressions of AREG and EREG were 0.55 ± 0.09 vs.0.99 ± 0.09,0.67 ± 0.10 vs.1.02 ± 0.02,protein expressions of EREG were 0.54 ± 0.09 vs.1.04 ± 0.13,all P ＜ 0.05.For LoVo cells,expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group,gene expression of AREG were 1.87 ± 0.39 vs.0.93 ± 0.23,protein expressions of AREG and EREG were 3.09 ±0.73 vs.1.11 ±0.21,1.53 ±0.19 vs.0.97 ± 0.23,all P ＜0.05.The regulating effect of AREG and EREG mRNA expression by FⅦa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression.For HT-29 cells,activation of EGFR pathway induced no significant TF mRNA expression,F Ⅶ mRNA expression was not detected.However,for LoVo cells,activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FⅦ,expressions were 1.53 ± 0.23 vs.1.00 ± 0.23,53.20 ± 6.08 vs.1.00 ± 0.15,all P ＜0.05.Conclusion:In colon cancer cell LoVo,when activated,TF/FⅦa pathway and EGFR pathway could interact through upregulating the other pathway's effectors,and mutant KRAS might play a critical role in the two pathways'cross talk.

OBJECTIVETo determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function.

METHODSThis was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated.

RESULTSPain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01).

CONCLUSIONSXFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.

Adult ; Aged ; Arthritis, Rheumatoid ; blood ; drug therapy ; pathology ; physiopathology ; Blood Sedimentation ; C-Reactive Protein ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Joints ; pathology ; Male ; Middle Aged ; Quality of Life ; Respiratory Function Tests ; Surveys and Questionnaires ; Treatment Outcome

OBJECTIVETo analyze and evaluate the application of spinning disk confocal microscopy and imaging analysis software in movement and phagocytosis of neutrophils.

METHODSNeutrophils were isolated from bone marrow by centrifugation on discontinuous Percoll gradient, and then were stained with PE Gr-1 antibody and mixed with FITC-labeled Zymosan A bioparticles. Multichannel time-lapse videos were captured by using the spinning disk confocal microscopy. The result was analyzed by using volocity and ImageJ software, the parameters associated with movement and phagocytosis of neutrophils were analyzed, including morphological changes, cell tracking, pseudopod dynamics, binding and phagocytosis index.

RESULTSMost neutrophils would be polarized in response to Zymosan particles during a short time. Binding and phagocytosis process occured in forty minutes.

CONCLUSIONA method of precisely quantifying the movement and phagocytosis of neutrophils using microscopic imaging and imaging analysis technique has been set up successfully. Using this method, biological activity and function of neutrophils can be evaluated visually and rapidly. The physiologically rapid response to Zymosan particles can be applied to the neutrophils function research in the future.

Antibodies ; Bone Marrow ; Cell Movement ; Humans ; Microscopy ; Neutrophils ; Phagocytosis ; Zymosan

OBJECTIVEA PCR-reverse dot blot hybridization (RDBH) assay was developed for rapid detection of rpoB gene mutations in 'hot mutation region' of Mycobacterium tuberculosis (M. tuberculosis).

METHODS12 oligonucleotide probes based on the wild-type and mutant genotype rpoB sequences of M. tuberculosis were designed to screen the most frequent wild-type and mutant genotypes for diagnosing RIF resistance. 300 M. tuberculosis clinical isolates were detected by RDBH, conventional drug-susceptibility testing (DST) and DNA sequencing to evaluate the RDBH assay.

RESULTSThe sensitivity and specificity of the RDBH assay were 91.2% (165/181) and 98.3% (117/119), respectively, as compared to DST. When compared with DNA sequencing, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the RDBH assay were 97.7% (293/300), 98.2% (164/167), and 97.0% (129/133), respectively. Furthermore, the results indicated that the most common mutations were in codons 531 (48.6%), 526 (25.4%), 516 (8.8%), and 511 (6.6%), and the combinative mutation rate was 15 (8.3%). One and two strains of insertion and deletion were found among all strains, respectively.

CONCLUSIONOur findings demonstrate that the RDBH assay is a rapid, simple and sensitive method for diagnosing RIF-resistant tuberculosis.

Antitubercular Agents ; pharmacology ; Drug Resistance, Bacterial ; Genotype ; Immunoblotting ; methods ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; drug effects ; genetics ; Polymerase Chain Reaction ; methods ; Rifampin ; pharmacology ; Sensitivity and Specificity ; Time Factors

Colon cancer may invade the adjacent organ in the absence of distant metastasis, which is called stage T4bM0 colon cancer according to the 7th edition of TNM staging system. It is not rare in clinical setting, and usually recognized intraoperatively. How to deal with this situation is a big challenge for the surgeons. It is difficult to distinguish between dense adhesion and cancerous invasion. Intraoperative biopsy should be avoided because of the risk of tumor cell dissemination and frozen often gives false-negative results. After evaluating the resectability of the tumor sufficiently, the surgeon should make every effort to do an en bloc multivisceral resection and to achieve a margin-free (R0) resection if there is no absolute contraindication. This effort will bring long-term prognosis benefit for the patients with stage cT4bM0 colon cancer.
Colonic Neoplasms ; surgery ; Humans ; Neoplasm Staging