Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Objective:To explore the predictive value of the difference in average CT attenuation values between renal pelvis urine and bladder urine on the risk of pyonephrosis, and to establish a nomogram model in combination with other parameters and to verify its predictive ability.Methods:The clinical data of patients with obstructive hydronephrosis who came to our hospital for emergency percutaneous nephrostomy (PCN) between January 2020 and December 2022 were retrospectively analyzed. There were 16 men and 33 women, with the age of (57.59, 14.67) years. Body mass index was (23.34, 3.11) kg/m 2. Urine nitrite was positive in 14 cases. Urine culture was positive in 21 cases. In the routine blood test, the median white blood cell count was 10.96 (7.21, 15.15) ×10 9/L, haemoglobin (115.08, 22.71) g/L and platelets (263.00, 97.20)×10 9/L. The difference in average CT attenuation values between renal pelvis urine and bladder urine (mean CT value of pyelonephritis-mean CT value of cysturia) was -2.19 (-7.04, 4.05) HU. Patients were divided into pyonephrosis group and hydronephrosis group according to whether the drainage fluid after PCN was pus. Single-factor and multi-factor logistic regression models were used to analyze the independent predictors of pyonephrosis and to construct nomograms. The discrimination of the model was assessed by the area under the curve (AUC) of the receiver operating characteristics (ROC), the accuracy by the calibration curve and the clinical efficacy by the decision curve analysis (DCA). Results:There were 49 cases in this study, 31 cases in the hydronephrosis group and 18 cases in the pyonephrosis group. The average CT attenuation values of renal pelvis urine were 3.35(0.56, 8.96) HU and 7.78 (3.75, 18.38) HU, respectively, and the difference between the two groups was statistically significant ( P=0.023). The average CT attenuation values of bladder urine were (7.81±6.15)HU and (7.22±7.50)HU, respectively, and there was no significant difference between the two groups ( P=0.780). The difference in average CT attenuation values between renal pelvis urine and bladder urine were -3.98(-7.54, 0.60)HU and 2.13 (-5.15, 9.36)HU, respectively, and the difference between the two groups was not statistically significant ( P=0.059); the white blood cells were 9.82(7.04, 12.46) ×10 9/L and 13.99(9.75, 18.44) ×10 9/L, respectively, and the difference between the two groups was statistically significant ( P=0.048). Platelet counts were (248.06±87.87)×10 9/L and (288.72±109.29)×10 9/L, respectively, and there was no statistical difference between the two groups ( P=0.189). The proportion of urine protein positive was higher in the pyonephrosis group (17 vs. 20, P=0.048). Between the two groups, sex, age, body mass index, clinical symptoms (with or without low back pain), surgical history of upper urinary tract stones, underlying diseases (including hypertension, diabetes, coronary heart disease, etc.), location of hydronephrosis (left, right, and both sides), reasons of obstruction [upper urinary tract stones, other factors (such as tumor, ureteral stricture, etc.)], haemoglobin, were not statistical different. There were no significant difference in blood glucose, blood potassium, blood sodium, urine leukocytes, urine erythrocytes, urine nitrite and urine culture ( P>0.05). Multivariate logistic regression analysis showed that the difference in average CT attenuation values between renal pelvis urine and bladder urine ( OR=1.196, 95% CI 1.055-1.437, P=0.018), white blood cells ( OR=1.252, 95% CI 1.036-1.615, P=0.038), and platelets ( OR=1.014, 95% CI 1.003-1.030, P=0.025) were independent predictors of pyonephrosis. According to the above indicators, the nomogram model was established and the AUC value of the model was 0.767 (95% CI 0.616-0.918), the sensitivity was 0.611 and the specificity was 0.935. The calibration curve showed that there is a good fit between the observed value and the predicted value. The DCA analysis showed that the nomogram model has a net gain in a wide threshold range, demonstrating its predictive accuracy and clinical practicality in predicting the risk of pyonephrosis. When the cut-off value of the difference between the average CT values of pyelonephritis and cystourethrosis was 6.54 HU, the AUC value of the independent prediction of pyonephrosis was 0.690(95% CI 0.564-0.816), the sensitivity was 0.444 and the specificity was 0.935. Conclusions:The difference in average CT attenuation values between renal pelvis urine and bladder urine is an independent risk factor for predicting pyonephrosis, and the nomogram constructed by combining it with white blood cells and platelets has a good predictive effect for predicting the risk of pyonephrosis. If the difference in average CT attenuation values between renal pelvis urine and bladder urine is greater than 6.54HU, it should be alert to the occurrence of pyonephrosis.

Objective:To investigate the methodological differences in the detection, the inflammatory markers and the pathogenic epidemiological characteristics of influenza A virus in clinical laboratories, in order to provide more diagnostic and epidemiological data for diagnosis and prevention for children with influenza A.Methods:A retrospective cross-sectional study was conducted to collect 96 731 patients with suspected influenza A from January 2016 to October 2024 in Nanyang City Center Hospital from the Clinical Laboratory Testing Information System, including 5 731 patients with confirmed influenza A, aged 5.2 (2.8, 43.7) years old. We analyzed the distribution of influenza A patients from age and mixed infections, the relationship between patient age and positive detection rate by restricted cubic spline (RCS), analyzed differences in testing methods used Kappa consistency testing and receiver operating characteristic (ROC) curves, established a model of inflammatory markers by logistic regression, as well as developed a prediction model and also the mutation of the hemagglutinin (HA) sequence of the influenza A subtype H3N2 virus using evolutionary tree analysis.Results:RCS analysis showed an inverted 'S' shaped non-linear relationship between the positive detection rate of influenza A and the age groups of the patients. Among the mixed infections, 1.43%(1 352/94 867) of the cases were combined with Mycoplasma pneumoniae infection. The Kappa values of reverse transcription PCR (RT-PCR) and serological indirect immunofluorescence assay (IFA) for detecting influenza A in nasopharyngeal swabs and alveolar lavage fluid in clinical laboratories were 0.632 and 0.809, respectively, and those of magnetic particle chemiluminescence assay were 0.614 and 0.668, respectively, and the area under curves in ROC curve of IFA and RT-PCR were 0.869 and 0.792, respectively. The inflammatory indexes were usually elevated in severe children compared with mild children. By binary logistic regression model analysis, neutrophil-to-lymphocyte ratio, D-dimer/fibrinogen and prognosis nutrition index were the risk factors and serum amyloid A/C reactive protein ratio was the protective factor for severe children with influenza A, and the OR values of the above factors were 1.760, 7.076, 1.045, and 0.719, respectively, and P<0.01. By the Bayesian Interdiction Criterion, the optimal seasonal autoregressive moving average mixed model for influenza A epidemics was ARIMA (1, 1, 1) (2, 1, 2) 12 with the highest prediction accuracy of 98.63%. The seven strains of H3N2 all belonged to the same isoforms, with nucleotide similarity of the HA gene ranging from 99.5% to 99.9%, and the glycosylation site, receptor-binding site, and the conserved amino acid residue Glycosylation sites, receptor binding sites and conserved amino acid residues remained unchanged. HA sequence analysis showed that the prevalent strains in Nanyang had undergone mutation to different degree compared with the vaccine strains. Conclusion:Scientific and rational testing and characteristic inflammatory markers in the clinical laboratory are of great clinical value in the diagnosis of children with severe influenza A. At the same time, the epidemiological monitoring of influenza A variants should be strengthened.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Objective:To explore the predictive value of the difference in average CT attenuation values between renal pelvis urine and bladder urine on the risk of pyonephrosis, and to establish a nomogram model in combination with other parameters and to verify its predictive ability.Methods:The clinical data of patients with obstructive hydronephrosis who came to our hospital for emergency percutaneous nephrostomy (PCN) between January 2020 and December 2022 were retrospectively analyzed. There were 16 men and 33 women, with the age of (57.59, 14.67) years. Body mass index was (23.34, 3.11) kg/m 2. Urine nitrite was positive in 14 cases. Urine culture was positive in 21 cases. In the routine blood test, the median white blood cell count was 10.96 (7.21, 15.15) ×10 9/L, haemoglobin (115.08, 22.71) g/L and platelets (263.00, 97.20)×10 9/L. The difference in average CT attenuation values between renal pelvis urine and bladder urine (mean CT value of pyelonephritis-mean CT value of cysturia) was -2.19 (-7.04, 4.05) HU. Patients were divided into pyonephrosis group and hydronephrosis group according to whether the drainage fluid after PCN was pus. Single-factor and multi-factor logistic regression models were used to analyze the independent predictors of pyonephrosis and to construct nomograms. The discrimination of the model was assessed by the area under the curve (AUC) of the receiver operating characteristics (ROC), the accuracy by the calibration curve and the clinical efficacy by the decision curve analysis (DCA). Results:There were 49 cases in this study, 31 cases in the hydronephrosis group and 18 cases in the pyonephrosis group. The average CT attenuation values of renal pelvis urine were 3.35(0.56, 8.96) HU and 7.78 (3.75, 18.38) HU, respectively, and the difference between the two groups was statistically significant ( P=0.023). The average CT attenuation values of bladder urine were (7.81±6.15)HU and (7.22±7.50)HU, respectively, and there was no significant difference between the two groups ( P=0.780). The difference in average CT attenuation values between renal pelvis urine and bladder urine were -3.98(-7.54, 0.60)HU and 2.13 (-5.15, 9.36)HU, respectively, and the difference between the two groups was not statistically significant ( P=0.059); the white blood cells were 9.82(7.04, 12.46) ×10 9/L and 13.99(9.75, 18.44) ×10 9/L, respectively, and the difference between the two groups was statistically significant ( P=0.048). Platelet counts were (248.06±87.87)×10 9/L and (288.72±109.29)×10 9/L, respectively, and there was no statistical difference between the two groups ( P=0.189). The proportion of urine protein positive was higher in the pyonephrosis group (17 vs. 20, P=0.048). Between the two groups, sex, age, body mass index, clinical symptoms (with or without low back pain), surgical history of upper urinary tract stones, underlying diseases (including hypertension, diabetes, coronary heart disease, etc.), location of hydronephrosis (left, right, and both sides), reasons of obstruction [upper urinary tract stones, other factors (such as tumor, ureteral stricture, etc.)], haemoglobin, were not statistical different. There were no significant difference in blood glucose, blood potassium, blood sodium, urine leukocytes, urine erythrocytes, urine nitrite and urine culture ( P>0.05). Multivariate logistic regression analysis showed that the difference in average CT attenuation values between renal pelvis urine and bladder urine ( OR=1.196, 95% CI 1.055-1.437, P=0.018), white blood cells ( OR=1.252, 95% CI 1.036-1.615, P=0.038), and platelets ( OR=1.014, 95% CI 1.003-1.030, P=0.025) were independent predictors of pyonephrosis. According to the above indicators, the nomogram model was established and the AUC value of the model was 0.767 (95% CI 0.616-0.918), the sensitivity was 0.611 and the specificity was 0.935. The calibration curve showed that there is a good fit between the observed value and the predicted value. The DCA analysis showed that the nomogram model has a net gain in a wide threshold range, demonstrating its predictive accuracy and clinical practicality in predicting the risk of pyonephrosis. When the cut-off value of the difference between the average CT values of pyelonephritis and cystourethrosis was 6.54 HU, the AUC value of the independent prediction of pyonephrosis was 0.690(95% CI 0.564-0.816), the sensitivity was 0.444 and the specificity was 0.935. Conclusions:The difference in average CT attenuation values between renal pelvis urine and bladder urine is an independent risk factor for predicting pyonephrosis, and the nomogram constructed by combining it with white blood cells and platelets has a good predictive effect for predicting the risk of pyonephrosis. If the difference in average CT attenuation values between renal pelvis urine and bladder urine is greater than 6.54HU, it should be alert to the occurrence of pyonephrosis.

Objective:To investigate the methodological differences in the detection, the inflammatory markers and the pathogenic epidemiological characteristics of influenza A virus in clinical laboratories, in order to provide more diagnostic and epidemiological data for diagnosis and prevention for children with influenza A.Methods:A retrospective cross-sectional study was conducted to collect 96 731 patients with suspected influenza A from January 2016 to October 2024 in Nanyang City Center Hospital from the Clinical Laboratory Testing Information System, including 5 731 patients with confirmed influenza A, aged 5.2 (2.8, 43.7) years old. We analyzed the distribution of influenza A patients from age and mixed infections, the relationship between patient age and positive detection rate by restricted cubic spline (RCS), analyzed differences in testing methods used Kappa consistency testing and receiver operating characteristic (ROC) curves, established a model of inflammatory markers by logistic regression, as well as developed a prediction model and also the mutation of the hemagglutinin (HA) sequence of the influenza A subtype H3N2 virus using evolutionary tree analysis.Results:RCS analysis showed an inverted 'S' shaped non-linear relationship between the positive detection rate of influenza A and the age groups of the patients. Among the mixed infections, 1.43%(1 352/94 867) of the cases were combined with Mycoplasma pneumoniae infection. The Kappa values of reverse transcription PCR (RT-PCR) and serological indirect immunofluorescence assay (IFA) for detecting influenza A in nasopharyngeal swabs and alveolar lavage fluid in clinical laboratories were 0.632 and 0.809, respectively, and those of magnetic particle chemiluminescence assay were 0.614 and 0.668, respectively, and the area under curves in ROC curve of IFA and RT-PCR were 0.869 and 0.792, respectively. The inflammatory indexes were usually elevated in severe children compared with mild children. By binary logistic regression model analysis, neutrophil-to-lymphocyte ratio, D-dimer/fibrinogen and prognosis nutrition index were the risk factors and serum amyloid A/C reactive protein ratio was the protective factor for severe children with influenza A, and the OR values of the above factors were 1.760, 7.076, 1.045, and 0.719, respectively, and P<0.01. By the Bayesian Interdiction Criterion, the optimal seasonal autoregressive moving average mixed model for influenza A epidemics was ARIMA (1, 1, 1) (2, 1, 2) 12 with the highest prediction accuracy of 98.63%. The seven strains of H3N2 all belonged to the same isoforms, with nucleotide similarity of the HA gene ranging from 99.5% to 99.9%, and the glycosylation site, receptor-binding site, and the conserved amino acid residue Glycosylation sites, receptor binding sites and conserved amino acid residues remained unchanged. HA sequence analysis showed that the prevalent strains in Nanyang had undergone mutation to different degree compared with the vaccine strains. Conclusion:Scientific and rational testing and characteristic inflammatory markers in the clinical laboratory are of great clinical value in the diagnosis of children with severe influenza A. At the same time, the epidemiological monitoring of influenza A variants should be strengthened.

The incidence of augmented renal clearance (ARC) in intensive care patients (ICU) is exceptionally high, and these patients are often co-morbid with infection. The occurrence of ARC will significantly increase the clearance rate of antibiotics, making it difficult for conventional doses to reach effective therapeutic concentrations and affect the patient's anti-infective treatment effect and prognosis. It can be seen that it is crucial to formulate a reasonable dosing regimen for ICU patients with ARC. Regrettably, few reports in China about the adjustment strategy of antibiotic dosing regimens for ARC patients. Therefore, this article reviews the domestic and foreign literature for reference to provide evidence for medical personnel to adjust the dose of antibacterial drugs for such patients.

【Objective】 To study the demographic characteristics of whole blood donors aged 56 to 60 in Guangzhou, so as to provide reference for smooth implementation of the recruitment and management of elderly blood donors in Guangzhou. 【Methods】 The data of whole blood donors, aged 56 to 60, in Guangzhou Blood Center from July 1, 2016 to June 30, 2021 were retrospectively analyzed, and such characteristics as the number of blood donations, gender, donation frequency, donation volume, occupation and educational background were analyzed. 【Results】 A total of 3 996 blood donors aged 56 to 60, including 3 013 males and 983 females, gave 14 416 donations during July 1, 2016 to June 30, 2021, with the proportion of 400 mL specification at 64.1% (6 999/10 918) of males, which was significantly higher than that of females 57.7% (2 017/3 498). The number of blood donors had been decreasing year by year, but the ratio of men to women was stable.The education background of blood donors were mainly high school, junior college, and undergraduate education, accounting for more than 60% in total, and the proportion of undergraduate and graduate degree trended to grow. Staff, workers, medical staff and civil servants were the majorities, and the proportion of medical staff trended to grow. 【Conclusion】 Male blood donors aged 56 to 60 in Guangzhou showed stronger intention to donate blood, and the proportion of blood donors with better education and medical staff was on the rise.

【Objective】 To investigate the changes of platelet, white blood cell, red blood cell counts, Hb and PCV before and after plateletpheresis donation. 【Methods】 10 444 platelet donors who donated platelet from Aug 1, 2019 to Jul 31, 2020 were selected as subjects, among which first-time donors were selected as control group and donors who donated twice or more as donation group. After matching gender and age using Propensity Score Matching method in the two groups, the changes of platelet, white blood cell, red blood cell counts, Hb and PCV of platelet blood donors were compared by t test. 【Results】 There were a slight increase in Plt (t=-6.651, P<0.05), a decrease in WBC (t=2.312, P<0.05), a decrease in hemoglobin(t=4.643, P<0.05), and no change in RBC (t=1.439, P>0.05) and in PCV (t=0.030, P>0.05) after plateletpheresis donation. 【Conclusion】 Plateletpheresis donation has an effect on some peripheral blood parameters, but within the normal reference range.

Objective:To evaluate the effect of combined use of Guben-Tiaoping Decoction on the success rate of stepwise treatment and life quality of asthma patients. Methods:A total of 76 patients with asthma in remission stage who were using ICS were divided into treatment group (38 cases) and control group(38 cases) according to random number table. Both groups were treated with ICS reduction based on the 2017 Gina Protocol. The treatment group was treated with Guben-Tiaoping Decoction for 12 weeks. The number of patients who were able to successfully complete the stepwise treatment after the end of the trial was calculated, the relevant indexes of Asthma Control Test (ACT), TCM Syndrome score, St. George’s respiratory questionnaire (SGRQ) and lung function were collected before and after treatment. Result:After 12 weeks’ treatment, the success rate of stepwise was 89.5% (34/38) in the treatment group and 78.9% (30/38) in the control group ( χ2=14.862, P=0.001). Meanwhile, the ACT score of the treatment group were better than those in the control group (Daytime symptoms t=-3.860, P=0.001, Dyspnea t=-2.007, P=0.40, Night waking t=-2.732, P=0.009, Reliever needed for symptoms t=-2.262, P=0.031, Control situation t=-6.994, P=0.001, Total Score t=-9.562, P=0.001). The score of TCM Syndrome in the treatment group was significantly lower than that of the control group ( P=0.001); PEF in treatment group [(6.92 ± 1.71) L vs. (5.84 ± 1.22) L; t=-2.880, P=0.005] was significantly better than that of the control group. Conclusion:Guben-Tiaoping Decoction is helpful to improve the success rate of ICS stepwise treatment and the life quality of patients.