Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Objective:To investigate syphilis infection and related factors among HIV-infected patients being followed up for more than one year in Zhejiang Province.Methods:Data were collected from the China Disease Control and Prevention Information System, and information such as demographic characteristics, viral load levels, and syphilis serologic test results was collected from HIV-infected persons who were diagnosed with HIV more than 1 year, aged ≥15 years with a current address in Zhejiang Province through December 31, 2022. The logistic regression model analyzed the prevalence of syphilis and the related factors. The SPSS 19.0 software was used for statistical analysis.Results:A total of 33 734 HIV-infected patients, with the prevalence of syphilis was 5.6% (1 879/33 734). Among the syphilis cases, the prevalence of syphilis was 6.4% (1 774/27 934) of males, 7.5% (640/8 543) of 25-34 years old age group, 7.6% (1 025/13 423) of unmarried, 8.3% (1 239/14 862) of homosexual transmission, 6.9% (214/3 080) with a non-local registered residence and 9.6% (602/6 267) with a history of STD before the HIV diagnosis. Multivariate Logistic regression analysis showed that participants who were male (a OR=2.19, 95% CI:1.77-2.72), 25-34 years old age group (a OR=1.80, 95% CI:1.47-2.20), homosexual transmission (a OR=1.67, 95% CI:1.49-1.88), with other provinces registered residence (a OR=1.26, 95% CI:1.09-1.47), and with a history of sexually transmitted disease (STD) before the HIV diagnosis (a OR=1.98, 95% CI:1.78-2.20) were associated with increased risk of syphilis. Being married (a OR=0.79, 95% CI:0.68-0.92) was associated with a decreased risk of syphilis. Conclusions:Syphilis infections were high in HIV-infected patients followed up more than one year in Zhejiang Province. It is recommended that syphilis surveillance and screening frequency should be strengthened among HIV-infected persons with characteristics such as male, homosexual transmission, and STD history.

AIM: To observe the effect of Esketamine combined with sufentanil on analgesia and emotion after thoracoscopic radical resection of lung cancer. METHODS: A total of 108 patients undergoing thoracoscopic radical resection of lung cancer were randomly divided into three groups: Esketamine plus sufentanil patient-controlled analgesia group (S group), low-dose sufentanil patient-controlled analgesia group (LC group) and high-dose sufentanil patient-controlled analgesia group (HC group). PCIA was performed after operation. The formula of analgesia pump in group S: Esketamine 1.2 mg/kg, sufentanil 1 μg/kg, LC group analgesic pump formula: sufentanil 1 μg/kg; Formula of analgesic pump in HC group: sufentanil 1.5 μg/kg; Tropisetron 10 mg was added to three groups of analgesia pumps, and normal saline was diluted to 100 mL. Observe the visual analogue scale (VAS) and Ramsay sedation score of resting and exercise pain at 6 h (T

Objective:To analyze the trend of liver cancer mortality in rural key areas of Jiangsu Province, Anhui Province, Shandong Province, and Henan Province (4 provinces) from 2009 to 2019 and to explore the influence of behavioral risk factors on liver cancer mortality and its lagging effect, and provide a reference for the prevention and treatment of liver cancer in China.Methods:Based on the 2009-2019 National Cause of Death Surveillance Database of the Chinese Center for Disease Control and Prevention, and the survey data of tumor and risk factor behavior of residents in key areas of 4 provinces, Joinpoint 4.2 software was used to calculate the average annual percentage change (AAPC) for assessing the temporal trend of standardized mortality of liver cancer; Chi-square test and trend Chi-square test were used to analyze the regional distribution difference and temporal change trend of behavioral habit factors. Stata 16 was used to establish a panel model to analyze the correlation and lagging effect of behavioral risk factors with liver cancer.Results:The standardized mortality rate of liver cancer in Jinhu County, Sheyang County, Lingbi County, Shou County, Mengcheng County, Wenshang County, Juye County, Luoshan County, Shenqiu County, and Xiping County showed a downward trend (AAPC<0, P<0.05) from 2009 to 2019. The consumption frequency of pickles/salted fish, red meat, and aquatic products showed a downward trend. The consumption frequency of healthy foods such as fresh vegetables, fresh fruits, and dairy products in all counties and districts showed an upward trend, and the consumption frequency of fried foods, kimchi, smoked foods, moldy foods, coffee, and soy products remained at a low level ( P<0.05); but the consumption frequency of soy products and dairy products was still <20.00%. Fried food, pickles/salted fish, current smoking rate, alcohol consumption rate, and unvaccinated hepatitis B vaccine rate were positively correlated with liver cancer death, and there was a lag effect, and the lag period was 4, 1, 6, 5, 4 years respectively. Conclusions:From 2009 to 2019, the mortality rate of liver cancer in rural key areas of 4 provinces shows a downward trend. There is a correlation and lagging effect between behavioral risk factors such as fried food, smoking, and alcohol consumption and liver cancer death.

OBJECTIVES: Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability. METHODS: A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema. RESULTS: HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group. CONCLUSIONS The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.
Adolescent ; Blood Glucose ; Blood Glucose Self-Monitoring ; Child ; Diabetes Mellitus, Type 1/drug therapy* ; Glucose ; Glycated Hemoglobin A/analysis* ; Humans ; Hypoglycemia/prevention & control* ; Hypoglycemic Agents/therapeutic use* ; Insulin/therapeutic use*

OBJECTIVE： To investigate the effects of Kangfuxin liquid on repairing cartilage defect model of knee osteoarthritis （KOA） in rabbits and its mechanism. METHODS： Totally 72 male New Zealand rabbits were selected and randomly divided into model control group and Kangfuxin low-dose， medium-dose， high-dose groups， with 18 rabbits in each group. A cartilage defect model of the medial femoral condyle of the right knee joint in rabbits was established by drilling after anesthesia surgery. Then the rabbits in each group were given medicine via articular cavity immediately. Kangfuxin low-dose， middle-dose and high-dose groups were given 20％， 40％， 80％ Kangfuxin liquid； model control group was given constant volume of normal saline consecutively， 0.2 mL/kg， once every 3 days. At 4th， 8th， 12th week after medication， the wound repair of cartilage defect in rabbits was observed. Immediately after medication and at 4th， 8th， 12th week after medication， repaired tissue of cartilage defect in rabbits was scored histologically with Wakitani scoring standard under light microscope. At 12th week after medication， pathological changes of repaired tissue of cartilage defect in rabbits were observed by Masson staining. The levels of NO， SOD and LPO in joint fluid and PYD in urine of rabbits were detected by ELISA. RESULTS： At 4th， 8th， 12th week after medication， compared with model control group， cartilage defects in rabbits were repaired well in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with immediately after medication and model control group at same time point， histomorphological score of repairing cartilage defect of knee joint in rabbits decreased significantly in Kangfuxin low-dose， medium-dose and high-dose groups （P＜0.05）. At 12th week after medication， compared with model control group， the histopathology degree of cartilage defect of knee joint in rabbits was significantly alleviated in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with model control group， the levels of NO and LPO in joint fluid and PYD level in urine were decreased to different extent in Kangfuxin low-dose， medium-dose and high-dose groups， while SOD level was increased to different extent； at 12th week after medication， the difference of each index has statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Kangangxin liquid can significantly repair cartilage defect of KOA cartilage defect model rabbits， the mechanism of which may be associated with increasing the expression of SOD and mediating NO-inhibited chondrocyte apoptosis.

Objective To summarize the clinical data of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD) patients and provide evidence for clinical diagnosis and treatment. Methods We retrospectively reviewed the clinical data of AOSD with MAS patients in the First Affiliated Hospital of Zhengzhou University from January 2012 to August 2018, and compared with patients with AOSD alone. Data were analyzed by t-test, Mann-Whitney U test, x2 test or Fisher exact test. Results A total of 14 AOSD with MAS patients were enrolled, accounting for 7.6％(14/185) of AOSD patients at the same period, including 2 males and 12 females. The median duration of AOSD in MAS was 1.3 (0.25, 4) months. Compared with the AOSD group, the age of onset was younger in the MAS group (t=-2.038, P=0.037), and the proportion of splenomegaly (t=9.020, P=0.003), pericardial effusion (t=8.663, P=0.003), pleural effusion (t=4.754, P=0.029) was higher. The white blood cell count (t=-4.171, P<0.01), hemoglobin level (t=-2.661, P=0.008), platelet count (t=-5.672, P<0.01), neutrophil count (t=-5.082, P<0.01), albumin (t=-3.426, P<0.01), fibrinogen (t=-5.986, P<0.01), ESR (t=-2.941, P=0.003), CRP (t=-2.014, P=0.044) was significantly decreased, ALT (t=-3.227, P<0.01), AST (t=-3.105, P=0.002), triglyceride (t=-5.612, P<0.01), ferritin>2000 μg/L (t=7.833, P=0.005) was significantly increased. Fourteen patients with AOSD complicated with MAS were treated with glucocorticosteroids, 5 with methylprednisolone, 8 with cyclosporine A, 8 with intravenous immunoglobulin (IVIG), 2 with etoposide, and 1 with tocilizumab. After treatment, 11 cases recovered and 3 cases died. Conclusion Younger AOSD patients tend to complicated with MAS, especially at the early course of the disease, and splenomegaly occur more frequently clinically compared to patients without MAS. When blood cell count, fibrinogen and ESR decreases, triglyceride and ferritin levels increases in AOSD patients, the occurrence of MAS is indicated. Timely treatment can improve the prognosis of patients.

Objective To investigate the clinical outcomes of extraperitoneal pelvic packing combined with temporary occlusion of abdominal aorta in treatment of pelvic fractures with hemodynamic instability.Methods A retrospective case series study was made on 14 patients with pelvic fractures with hemodynamic instability managed by extraperitoneal pelvic packing plus temporary occlusion of abdominal aorta between December 2006 and December 2013.There were ten males and four females,with mean age of 38.2 years old (range,18-63 years).The fractures were classified according to the Tile classification,including two patients with type B1,two with type B2.2,one with type C1.1,two with type C1.2,two with type C1.3,three with type C2,and two with type C3.In addition,10 patients were with closed pelvic fractures and four with open pelvic fractures.All patients were diagnosed as hypovolemic shock once they were admitted.Every patient was given anti-shock treatment,temporary occlusion of abdominal aorta,and extraperitoneal pelvic packing instantly,in order to control hemorrhage of pelvic fracture after they were admitted.The operation time,red blood cell transfusion volume,preoperative and postoperative blood pressures,heart rates as well as other relevant parameters concerning death and survival were recorded and compared.Postoperative infection and wound healing status were recorded as well.Results The operation time was 50-70 minutes (mean,61 minutes).After surgery,the length of ICU stay was (10.9 ± 9.8) days and hospital stay was (23.1 ± 14.9) days.Red blood cell transfusion volume before and after surgery was (17.7 ± 2.2)U and (8.4± 1.7)U,respectively (P ＜ 0.05).The parameters of systolic pressures varied from preoperative (63.6 ± 2.1) mmHg to postoperative (90.9 ± 1.1) mmHg,and the parameters of heart rates declined from preoperative (106.2 ± 5.9) beats/min to postoperative (94.0 ± 6.2) beats/min,(P ＜ 0.05).Ten patients were available for follow-up of 8-24 months (mean,11.5 months).There were four deaths (29％) postoperatively,among which three were died from multisystem and organ failure,and one from severe brain injury.There were statistically significant differences between the survivors and the deaths in terms of time from injury to operation,average systolic pressures,and average heart rates (P ＜ 0.05).None had complications and wound was well healed.Conclusion For pelvic fractures with hemodynamic instability,extraperitoneal pelvic packing plus temporary occlusion of abdominal aorta has advantages of short manipulation time and effective outcomes,which can control the hemorrhage of pelvic fracture and ameliorate the hemodynamic status.

Objective To investigate the expression of programmed death receptor-1 (PD-1) in CD8+ T cells and FoxP3+CD4+ cells in patients with primary biliary cholangitis (PBC).Methods The peripheral blood and clinical data of 69 PBC patients in Peking Union Medical College Hospital and 58 health controls (HC) were collected.They were divided into initial treatment group and follow-up group according to whether they were treated or not.Patients in the treatment group were further divided into the refractory group and stable group according to treatment response.Flow cytometry was used to detect the expression of PD-1 in CDS+T cells and FoxP3+CD4+ cells.T-test and Person correlation analysis were used for data analysis.Results The PD-1 expression in peripheral blood mononuclear cells (PBMCs) of 69 PBC patients (12±9)％ was lower than that of HC (20±12)％ (t=-3.687,P＜0.01).The percentage of PD-1+ in FoxP3+ CD4+T cells was significantly increased in PBC (5.6±3.7)％ than HC (7.4±2.4)％ (t=2.048,P＜0.01).The proportion of CD8+T cells,PD-1 expression in CD8+T cells and the proportion of FoxP3+CD4+ cells weren't correlated with clinical parameters (P＞0.05).There was a negative correlation between the expression of PD-1 cells in FoxP3+CD4+ cells and GLOBE score (r=-0.307,P＜0.05).Conclusion The expression of PD-1 in peripheral CD8+T lymphocytes of PBC patients is lower than that of HC,and decreases more significantly in the refractory group.The expression of PD-1 on FoxP3+CD4+T cells is higher than that in HC,and is negatively correlated with the prognostic GLOBE score.It suggests that PD-1/PD-L1 pathway participates in the immune mechanism of PBC.

Objective To investigate the health related quality of life score [primary biliary cholangitis (PBC)-40] in patients with PBC,and the relationship between PBC-40 and clinical presentations.Methods The PBC-40 score and clinical presentations in PBC patients (n=65) were adapted in this study.Patients were divided into the untreated group and the treated group,and the treated group was further divided into ursodesoxycholic acid (UDCA) response group and UDCA non-response group.PBC-40 scores of different groups were analyzed by t-test and the relationship between PBC-40 and clinical presentations were analyzed with Pearson's test.Results Dimensions of PBC-40 scores of this group of patients were as follows:symptoms were (15.8±4.1) points,itch was (4.9±2.8) points,atigue was (23.8±8.9) points,cognitive dysfunction score was (11.4±4.7) points,social activity score was (17.0±7.5) points,and the emotion score was (6.5±3.1) points.The untreated group had higher emotion scores than the treated group (t=2.024,P=0.045).Compared with the UDCA response group,UDCA non-response group had higher scores in cognitive,social and emotion dimension (t =2.126,2.309,2.062,respectively,P=0.039,0.025,0.045,respectively).Itch score was significantly correlated with total bilirubin (TBil),direct bilirubin (DBil),alkaline phosphatase (ALP) and total bile acid (TBA) (r=0.349,0.345,0.324,0.427,respectively,P＜0.01),while the social scores were correlated with TBil,DBil,aspartate aminotransferase (AST) and TBA (r=0.361,0.383,0.316,0.331,P＜0.01) and emotion scores were associated with ALT,TBil,GGT,ALP,AST and TBA (r=0.332,0.430,0.265,0.326,0.297,0.353,P＜0.05).ConclusionPBC-40 can be used as a health-related quality of life assessment for PBC patients inChinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health quality of life in PBC patients.Conclusion PBC-40 can be used as a health-related quality of life assessment for PBC patients in Chinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health related quality of life in PBC patients.