The patient,male,69-year-old,was given 10mg of dapagliflozin tablets qd for type 2 diabetes mellitus.He de-veloped hemolytic anemia with jaundice about 7 days after oral administration.The occurrence,diagnosis,treatment and follow-up of the adverse drug reactions were retrospectively analyzed.The correlation between dapagliflozin and adverse drug reactions was e-valuated,and the possible mechanism of the adverse drug reactions was discussed through literature analysis.This case of adverse drug reactions is rare.We suggested that the monitoring of the adverse reactions of blood system should be strengthened to ensure the safety of clinical use of dapagliflozin.

The patient,male,69-year-old,was given 10mg of dapagliflozin tablets qd for type 2 diabetes mellitus.He de-veloped hemolytic anemia with jaundice about 7 days after oral administration.The occurrence,diagnosis,treatment and follow-up of the adverse drug reactions were retrospectively analyzed.The correlation between dapagliflozin and adverse drug reactions was e-valuated,and the possible mechanism of the adverse drug reactions was discussed through literature analysis.This case of adverse drug reactions is rare.We suggested that the monitoring of the adverse reactions of blood system should be strengthened to ensure the safety of clinical use of dapagliflozin.

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:To explore the clinical characteristics of tenofovir disoproxil fumarate (TDF)-related Fanconi syndrome (FS) in patients with HIV infection/AIDS (HIV/AIDS).Methods:The medical records of patients with HIV/AIDS who were hospitalized in Yunnan Provincial Hospital of Infectious Diseases from December 2017 to February 2021, treated with antiretroviral therapy (ART) containing TDF, and diagnosed as FS were collected by searching hospital information system. Information such as gender, age, body weight, body mass index (BMI), ART treatment regimen and period, time of FS diagnosis, main clinical characteristics, results of laboratory test at admission and discharge, dual energy X-ray bone mineral density (BMD) test results, and interventions and outcomes were retrospectively analyzed.Results:A total of 16 HIV/AIDS patients were diagnosed with TDF-related FS in the setting period, including 6 patients with complete FS and 10 with incomplete FS. FS were accompanied with chronic hepatitis C, hypertension, liver cancer, or depression in 7 patients. Sixteen patients received ART containing TDF for a minimum of 20 months and a maximum of 168 months with an average time of 68 months. The initial symptoms of FS were bone pain, fatigue, nausea, anorexia, polydipsia, polyuria, weight loss, etc. The time from initial symptoms to diagnosis of FS was 2 weeks at least, 24 weeks at most, with an average time of 7 weeks. Laboratory test results were as follows: all 16 patients had positive urine glucose under normoglycemic conditions and 14 patients had positive urine protein; 11, 11, 4, and 4 patients had low urine phosphorus, hypocalciuria, hypokalemia, and hyponatruria, respectively; 13, 12, 8, and 7 patients had hypophosphatemia, hypokalemia, hypocalcemia, and hyponatremia, respectively; 11 patients had serum creatinine increase; 10 patients had serum uric acid decrease; 1 patient had serum uric acid increase. Dual energy X-ray BMD detection was performed in 15 patients, of which 2, 2, and 11 patients had normal, reduced, and osteoporotic BMD, respectively. After diagnosis of TDF-related FS, 16 patients stopped using TDF immediately. After replacement of ART protocol without TDF and symptomatic treatment for an average time of 29 days, the above symptoms were alleviated, and some laboratory test indicators returned to the reference value range. The prognosis was good.Conclusions:TDF-related FS mostly occurs within 68 months of drug use. The clinical symptoms of FS are nonspecific. Laboratory tests show that urine glucose is positive under normal blood glucose. Most of the patients have low blood phosphorus, low urine phosphorus, hypocalciuria, and osteoporosis. The prognosis is better after discontinuing TDF, replacing therapy with ART regimen without TDF, and giving symptomatic treatments.

Objective:To explore the clinical characteristics of tenofovir disoproxil fumarate (TDF)-related Fanconi syndrome (FS) in patients with HIV infection/AIDS (HIV/AIDS).Methods:The medical records of patients with HIV/AIDS who were hospitalized in Yunnan Provincial Hospital of Infectious Diseases from December 2017 to February 2021, treated with antiretroviral therapy (ART) containing TDF, and diagnosed as FS were collected by searching hospital information system. Information such as gender, age, body weight, body mass index (BMI), ART treatment regimen and period, time of FS diagnosis, main clinical characteristics, results of laboratory test at admission and discharge, dual energy X-ray bone mineral density (BMD) test results, and interventions and outcomes were retrospectively analyzed.Results:A total of 16 HIV/AIDS patients were diagnosed with TDF-related FS in the setting period, including 6 patients with complete FS and 10 with incomplete FS. FS were accompanied with chronic hepatitis C, hypertension, liver cancer, or depression in 7 patients. Sixteen patients received ART containing TDF for a minimum of 20 months and a maximum of 168 months with an average time of 68 months. The initial symptoms of FS were bone pain, fatigue, nausea, anorexia, polydipsia, polyuria, weight loss, etc. The time from initial symptoms to diagnosis of FS was 2 weeks at least, 24 weeks at most, with an average time of 7 weeks. Laboratory test results were as follows: all 16 patients had positive urine glucose under normoglycemic conditions and 14 patients had positive urine protein; 11, 11, 4, and 4 patients had low urine phosphorus, hypocalciuria, hypokalemia, and hyponatruria, respectively; 13, 12, 8, and 7 patients had hypophosphatemia, hypokalemia, hypocalcemia, and hyponatremia, respectively; 11 patients had serum creatinine increase; 10 patients had serum uric acid decrease; 1 patient had serum uric acid increase. Dual energy X-ray BMD detection was performed in 15 patients, of which 2, 2, and 11 patients had normal, reduced, and osteoporotic BMD, respectively. After diagnosis of TDF-related FS, 16 patients stopped using TDF immediately. After replacement of ART protocol without TDF and symptomatic treatment for an average time of 29 days, the above symptoms were alleviated, and some laboratory test indicators returned to the reference value range. The prognosis was good.Conclusions:TDF-related FS mostly occurs within 68 months of drug use. The clinical symptoms of FS are nonspecific. Laboratory tests show that urine glucose is positive under normal blood glucose. Most of the patients have low blood phosphorus, low urine phosphorus, hypocalciuria, and osteoporosis. The prognosis is better after discontinuing TDF, replacing therapy with ART regimen without TDF, and giving symptomatic treatments.

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: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 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.