Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective:This study was to systematically update the economic evaluation evidence of colorectal cancer screening in mainland China.Methods:Based on a systematic review published in 2015, we expanded the scope of retrieval database (PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, CBM) and extended it to December 2018. Focusing on the evidence for nearly 10 years (2009-2018), basic characteristics and main results were extracted. Costs were discounted to 2017 using the consumer price index of medical and health care being provided to the residents, and the ratio of incremental cost-effectiveness ratio (ICER) to per capita GDP in corresponding years were calculated.Results:A total of 12 articles (8 new ones) were included, of which 9 were population-based (all cross-sectional studies) and 3 were model-based. Most of the initial screening age was 40 years (7 articles), and most of the frequency was once in a lifetime (11 articles). Technologies used for primary screening included: questionnaire assessment, immunological fecal occult blood test (iFOBT) and endoscopy. The most commonly used indicator was the cost per colorectal cancer detected, and the median (range) of the 20 screening schemes was 52 307 Chinese Yuan (12 967-3 769 801, n=20). The cost per adenoma detected was 9 220 Yuan (1 859-40 535, n=10). In 3 articles, the cost per life year saved (compared with noscreening) was mentioned and the ratio of ICER to GDP was 0.673 (-0.013-2.459, n=11), which was considered by WHO as "very cost-effective" ; The range of ratios overlapped greatly among different technologies and screening frequencies, but the initial age for screening seemed more cost-effective at the age of 50 years (0.002, -0.013-0.015, n=3), than at the 40 year-olds (0.781, 0.321-2.459, n=8). Conclusions:Results from the population-based studies showed that the cost per adenoma detected was only 1/6 of the cost per colorectal cancer detected, and limited ICER evidence suggested that screening for colorectal cancer was generally cost-effective in Chinese population. Despite the inconclusiveness of the optimal screening technology, the findings suggested that the initial screening might be more cost-effective at older age. No high-level evidence such as randomized controlled trial evaluation was found.

Objective:To analysis the clinical and follow-up data of the early colorectal carcinoma (ECC) after endoscopic resection, and explore the long-term outcome of patients who underwent the endoscopic resection.Methods:During June 2008 to June 2016, data of endoscopic resection for 550 cases of ECC were collected, including general information and follow-up data. The influence factors of disease-free survival rate of ECC after endoscopic resection were analyzed and the risk factors on long-term outcomes such as submucosa invasion depth, poorly differentiated adenocarcinoma, vascular invasion and positive vertical margin were investigated.Results:The mean follow-up time of 550 patients treated with endoscopy was (60.7±36.8) months. Among them, 433 cases were high-level intra-mucosal neoplasia, 117 cases were submucosa invasion carcinoma (the invasion depth <1 000 μm were 33 cases, ≥1 000 μm were 84 cases), 461 cases were curative resection, while 89 cases were non-curative resection. During the follow-up, 6 patients occurred recurrence or metastasis, including 2 patients with local recurrence (1 patient accompanied by lymph node metastasis) and 4 patients with lymph node metastasis (2 patients accompanied by distant metastasis). The overall 5-years disease-free survival rate was 98.8%, the 5-years disease-free survival rate was 100.0% for patients with curative resection and 93.3% for patients with non-curative resection. A total of 89 cases underwent non-curative resection were accompanied with invasion depth ≥1 000 μm, vascular invasion, poorly differentiated adenocarcinoma and positive vertical margin. Among them, 62 cases were accompanied with 1 risk factor, 23 cases with 2 risk factors and 4 cases with 3 risk factors. The risks of lymph nodes and distant metastasis raised with the increase of risk factors.Conclusions:The incidence of lymph node metastasis in ECC is extremely low. Endoscopic treatment can achieve a good long-term outcome. Close follow-up should be conducted after endoscopic treatment, and additional treatment should be selected reasonably for the early colorectal carcinoma after endoscopic non-curative resection to improve the therapeutic efficacy of endoscopic resection.

Objective:To analysis the clinical and follow-up data of the early colorectal carcinoma (ECC) after endoscopic resection, and explore the long-term outcome of patients who underwent the endoscopic resection.Methods:During June 2008 to June 2016, data of endoscopic resection for 550 cases of ECC were collected, including general information and follow-up data. The influence factors of disease-free survival rate of ECC after endoscopic resection were analyzed and the risk factors on long-term outcomes such as submucosa invasion depth, poorly differentiated adenocarcinoma, vascular invasion and positive vertical margin were investigated.Results:The mean follow-up time of 550 patients treated with endoscopy was (60.7±36.8) months. Among them, 433 cases were high-level intra-mucosal neoplasia, 117 cases were submucosa invasion carcinoma (the invasion depth <1 000 μm were 33 cases, ≥1 000 μm were 84 cases), 461 cases were curative resection, while 89 cases were non-curative resection. During the follow-up, 6 patients occurred recurrence or metastasis, including 2 patients with local recurrence (1 patient accompanied by lymph node metastasis) and 4 patients with lymph node metastasis (2 patients accompanied by distant metastasis). The overall 5-years disease-free survival rate was 98.8%, the 5-years disease-free survival rate was 100.0% for patients with curative resection and 93.3% for patients with non-curative resection. A total of 89 cases underwent non-curative resection were accompanied with invasion depth ≥1 000 μm, vascular invasion, poorly differentiated adenocarcinoma and positive vertical margin. Among them, 62 cases were accompanied with 1 risk factor, 23 cases with 2 risk factors and 4 cases with 3 risk factors. The risks of lymph nodes and distant metastasis raised with the increase of risk factors.Conclusions:The incidence of lymph node metastasis in ECC is extremely low. Endoscopic treatment can achieve a good long-term outcome. Close follow-up should be conducted after endoscopic treatment, and additional treatment should be selected reasonably for the early colorectal carcinoma after endoscopic non-curative resection to improve the therapeutic efficacy of endoscopic resection.

Objective: To acknowledge the availability and rates of annual transition of outcomes during the progression and regression stages of colorectal cancer (CRC) and related diseases, by pooling global follow-up studies on the natural history of CRC. Methods: Till March, 2017, data was collected through systematic literature review over multiple databases, including PubMed, Embase, Cochrane and Chinese Biology Medicine (CBM) disc. Information regarding the characteristics, classification system of health states, related outcomes and incidence rates on CRC or high-risk adenoma for the surveillance cohorts of the studies, were extracted and summarized. Both Meta and sensitivity analyses were performed on those outcomes if they appeared in more than 3 studies, using the random effects model. Annual transition rate with 95%CI was used to estimate each of the outcomes, Quality of the studies was assessed, using the Newcastle-Ottawa Scale. Results: A total of 29 cohort studies were included, with the mean follow-up period as 5.7 years. All studies except one, focused on adenoma-carcinoma pathway and reported the outcome parameters of adenomas by different risk, and some reported the findings on different sizes (n=6) of adenomas. These cohorts were divided into three groups (normal status, with low-risk or high-risk adenoma) according to the status of baseline endoscopic pathologic findings. Their available outcome parameters, corresponding number of involved articles, aggregated sample size and pooled annual transition rates were presented. Six parameters were obtained in the normal cohorts, including those from normal to low-risk adenoma (16 articles, 58 235, 0.030: 0.024-0.037), to high-risk adenoma (17 articles, 62 089, 0.003: 0.002-0.004), to diminutive adenoma (<5 mm, 4 articles, 1 277, 0.021: 0.013-0.029), to small adenoma (6-9 mm, 4 articles, 1 277, 0.006: 0.001-0.010), to large adenoma (≥10 mm, 7 articles, 3 531, 0.002: 0.000-0.003) and to CRC (19 articles, 104 836, 0.000 3: 0.000 2-0.000 5). Three parameters were obtained in low-risk adenoma in cohorts with polypectomy findings, including recurrence (9 articles, 4 788, 0.109: 0.062-0.157) from low-risk adenoma after polypectomy to high-risk adenoma (10 articles, 5 736, 0.009: 0.004-0.013) and to CRC (12 articles, 11 347, 0.000 6: 0.000 4-0.000 8). Three parameters were obtained on high-risk adenoma from cohorts with polypectomy findings, including recurrence (12 articles, 7 030, 0.038: 0.028-0.048) from high-risk adenoma after polypectomy to low-risk adenoma (8 articles, 2 489, 0.133: 0.081-0.185) and CRC (14 articles, 14 899, 0.002: 0.001-0.003). Except for normal to low-risk adenomas, results from the sensitivity analysis for the other parameters showed stable. Of the included studies, two presented incidence rates of CRC in different clinical stages and the another two were focusing on the parameters related to serrated pathway. Conclusions Globally, follow-up studies reported data on natural history of colorectal cancer is of paucity. Compared to the "adenoma-carcinoma" pathway, transition parameters of the serrated lesion pathway are more limited. This Meta-analysis provided convincing evidence for optimizing the strategies regarding follow-up program on the disease, using the baseline endoscopic findings from global CRC Screening Program. These results also offered strong data-related support for Chinese population- specific interventional model on colorectal cancer.

Objective:To investigate targeted therapy of ovarian cancer with new fusion proteins that were produced by fusing the first 390 amino acids of diphtheria toxin(DT390)to the TMTP1 peptide.Methods:The cisplatin-resistant cell line,C13*,and cisplatin-sensi-tive cell line,OV2008,were selected as models and divided into control,TMTP1,DT390-TMTP1,DT390-biTMTP1,and DT390-triTMTP1 groups.Laser scanning confocal microscopy was used to observe nuclear morphology.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide(MTT)and flow cytometry assays were used to detect cell survival and apoptosis,respectively.The formation of subcu-taneous tumors in nude mice following injection of C13*cells was used to observe the formation and growth of ovarian cancer.Apop-tosis of cells in the subcutaneous tumor tissue was detected by the terminal deoxynucleotidyl transferase dUTP nick-end labeling(TU-NEL)assay.Results:Laser scanning confocal microscopy showed that DT390-biTMTP1 and DT390-triTMTP1 induced nuclear shrinkage and fragmentation.The MTT assay showed that cell survival was obviously reduced with increasing concentrations of DT390-biTMTP1 and DT390-triTMTP1. Flow cytometry revealed that DT390-biTMTP1 and DT390-triTMTP1 significantly increased cell apoptosis (P<0.05).The apoptosis rates of the DT390-biTMTP1 and DT390-triTMTP1 groups were 66.0%±12.0% and 72.9%±4.6%,respectively.These were higher than the 55.5%±8.9% and 65.1%±9.8% obvserved in OV2008 cells.DT390-biTMTP1 and DT390-triTMTP1 significantly in-hibited the tumor formation (P<0.01) and growth (P<0.05), and increased apoptosis (P<0.05) of subcutaneous tumors. However, DT390-TMTP1 had insignificant effects on C13*and OV2008 cells.Conclusions:DT390-biTMTP1 and DT390-triTMTP1 preferentially tar-geted and inhibited ovarian cancer cells.These fusion proteins may be a promising strategy for clinical therapy of ovarian cancer.

Objective: To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods: Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios (HRs) and 95% CIs by Cox proportional regression model. Results: Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P=0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P=0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer (HR=0.44, 95% CI: 0.20-0.96, P=0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time (HR=1.74, 95% CI: 1.06-2.84, P=0.028; HR=1.64, 95% CI: 1.01-2.66, P=0.046; HR=1.71, 95% CI: 1.01-2.91, P=0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis. Conclusions Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.

Objective To investigate the pattern of nodal recurrence after curative resection in adenocarcinoma of the gastroesophageal junction ( AGE ) , and to provide a basis for delineation of the radiation range in the high-risk lymphatic drainage area.Methods A retrospective analysis was performed in 78 patients with locally advanced AGE who were newly treated in our hospital from January 2009 to December 2013 and had complete clinical data.All patients received curative resection and were pathologically diagnosed with stage T3/T4 or N (+) AGE.Those patients were also diagnosed with SiewertⅡor Ⅲ AGE by endoscopy, upper gastroenterography, macroscopic examination during operation, and pathological specimens.None of the patients received preoperative or postoperative radiotherapy.All patients were diagnosed by imaging with postoperative nodal recurrence.The computed tomography images of those
patients were accessible and had all the recurrence sites clearly and fully displayed.Results The median time to recurrence was 10 months ( 1-48 months) , and 90%of the recurrence occurred within 2 years after surgery.The lymph nodes with the highest risk of recurrence were No.16b1( 39%) , No.16a2( 37%) , No.9 (30%), and No.11p (26%), respectively.There was no significant difference in the recurrence rate within each lymphatic drainage area between patients with SiewertⅡandⅢAGE ( P=0.090-1.000) .The lymph nodes with the most frequent recurrence were No.16b1, No.16a2, No.9, No.16b2, No.11p, and No.7 in patients with stage N3 AGE and No.11p, No.16b1, No.16a2, No.9, No.8, and No.7 in patients with stage non-N3 AGE.Patients with stage N3 AGE had a significantly higher recurrence rate in the para-aortic regions (No.16a2-b2) than those with stage non-N3 AGE (67%vs.33%, P=0.004, OR=4.00, 95% CI=1.54-10.37) .Conclusions The lymph nodes with the highest risk of recurrence are located in the celiac artery, proximal splenic artery, and retroperitoneal areas ( No.16a2 and No.16b1) in patients with SiewertⅡorⅢlocally advanced AEG.Moreover, patients with stage N3 AGE have a higher risk of retroperitoneal recurrence.The above areas should be involved in target volume delineation for postoperative radiotherapy.

Background Studies indicate that the decline of androgen level affects the secretion function of epithelial cells of meibomian glands and lacrimal glands ,which results in the abnormality of tear quality and quantity.However,whether androgen level regulates the mucin adhesion to ocular surface is still not elucidated.Objective This study was to investigate the tear functional changes and corneal ultrastructural changes in castrated male mice.Methods Fifty-six SPF male BALB/c mice were devided into normal control group, sham group, and orchectomy 1-week group, orchectomy 2-week group, orchectomy 4-week group, orchectomy 6-week group, orchectomy 8-week group according to random number table.Orchectomy was performed in the mice of the orchectomy 1-,2-,4-,6-and 8-week group,and only incision rather than enucleation of testis was carried out in the mice of the sham group.Peripheral venous blood samples were collected during eyeball enucleation in all the mice and serum androgen concentration was detected by radioimmunoassay.Tear secretion level was measured with phenol red thread.Break-up time of tear film (BUT) was tested,and corneal inflorescence staining was scored based on the criterion of Toshida.The corneas of all the mice were collected for ultrastructural examination under the transmission electron microscope.The study complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results Mouse serum androgen concentration was (573.87±6.74) ng/μl in the normal control group and (579.74-±8.24)ng/μl in the sham group, and there was no significant difference between these two groups (t =1.432, P =0.251) , however, the serum androgen concentration was 0 ng/μl in all castrated mice after orchectomy.The tear secretion levels were (5.26 ± 0.99), (4.89 ± 0.56), (4.62 ± 0.83), (4.28 ± 0.63), (3.36 ± 0.56),(2.60±0.27) and (2.08 ±0.35) mrn/5 minutes in the normal control group, sham group and orchectomy 1-, 2-, 4-,6-and 8-week groups, respectively, and the tear secretion levels were significantly lower in the orchectomy 2-, 4-,6-and 8-week groups than those in the normal control group (all at P＜0.05).The BUT were (68.33±12.86), (62.47± 3.75),(58.67±10.03), (47.17±7.64) ,(39.51±3.39),(32.67±3.88) and (31.00±2.36) seconds in the normal control group, sham group and orchectomy 1-, 2-, 4-, 6-and 8-week groups, respectively, and the BUTs were significantly shorter in the orchectomy 2-,4-, 6-and 8-week groups than those in the normal control group (all at P＜0.05).The fluorescein stain score of corneal epithelium was gradually increased with the lapse of castrated time.The decrease of number,shortening and edema of microvilli as well as separation of desmosomes of corneal epithelial cells were found under the transmission electron microscope in castrated mice.Conclusions Decreasing of serum androgen level, declining of aqueous tears,instability of tear film and damage of corneal epithelial cell ultrastructures occur in castrated male mice, and these manifestations are similar to dry eyes.

Objective: To analyze the efficiency characteristics and trend of tertiary general public hospitals from both static and dynamic perspectives. Methods: After collecting data of personnel, equipment, assets, health services and other inputs-output indicators from 50 tertiary public hospitals from 2006 to 2012 , this paper uses C2 R-DEA and BC2-DEA models, as well as Malmquist Index model to build suitable analysis model. Results:About 10%~12% of the sample hospitals are in a relatively effective operational state, and the mean values of allocation effi-ciency and scale efficiency are 0. 956 and 0. 943, respectively, which are close to the efficient frontier. The mean values of pure technical efficiency, technical efficiency, cost efficiency and overall efficiency are 0. 796, 0. 784, 0. 714 and 0. 714, respectively, which are relatively poor compared with the efficiency frontier. Moreover, the number of hospitals that are in the state of diminishing returns to scale increased from 7 . 69% to 26 . 31%, while the number of hospitals that are in the state of increasing returns to scale decreased from 80. 77% to 58. 34%. The changes in techno-logical progress, Malmquist productivity index, technical efficiency index, pure technical efficiency index and scale effi-ciency index remained a relatively stable consistency, and showed continuous improvement and steady development trend. Conclusion:Tertiary general public hospitals are facing the transformation of driving force for development and incentive mechanisms. This needs not only to change the management concept and development mode of the hospitals, but also to build evaluation standards of optimum efficiency that are relevant to the structure, process and outcome, in order to pro-mote the transformation of hospital governance and development model that includes the functions of government.