[Purpose]To analyze the trends of mortality and probability of premature mortality caused by colorectal cancer in Jinshan District of Shanghai from 1980 to 2023.[Methods]The death database of Jinshan District from 1980 to 2023 were established based on the death reports from the medical institutions and public security bureau at all levels.The crude mortality rate,age-standardized mortality rate by Chinese standard population and world standard population(ASRC and ASRW),age-specific mortality rate,probability of premature mortality,annual percentage change(APC)and average annual percentage change(AAPC)of colorectal cancer were calculated.[Results]The crude mortality rate of colorectal cancer increased from 1980 to 2023(AAPC=2.36％,P＜0.001)and the ASRW of colorectal cancer decreased at the same period(AAPC=-1.02％,P=0.003).The ASRW of colorectal cancer in male and female showed a decreasing trend from 1990 to 1999(APC=-5.08％,-7.85％,P=0.007,0.011),but there was no significant change in other periods.The age-specific mortality rate increased with age and reached the peak at the age group of 70～74 years old during 1980-1989,75～79 years old during 1990-1999,80～84 years old during 2000-2009 and 2010-2019,85 years old and above during 2020-2023(109.22/105,77.56/105,113.78/105,172.82/105 and 236.58/105,respectively).The probability of premature mortality of colorectal cancer decreased in male and female(AAPC=-1.10％,-2.41％,P=0.047,＜0.001),but there was no change after the year of 2000.[Conclusion]The overall mortality rate of colorectal cancer in Jinshan District showed a decreasing trend from 1980 to 2023,but the standardized mortality rate and the probability of premature mortality had not shown a significant downward trend since 2000.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Objective:To investigate the molecular mechanism of Xiaoshuantongmai Decoction(XSTMD)targeting JAK2/STAT3 signaling pathway to regulate the function of dendritic cells(DCs)in treatment of deep vein thrombosis(DVT).Methods:After treatment of DVT with XSTMD,expressions of fibrinogen beta chain(FGB)and D-dimer(D2D)protein in plasma of patients with DVT were detected by ELISA,proportion of plasmacytoid dendritic cell(pDC)and conventional dendritic cell(cDC),and expression of HLA-DR protein in peripheral blood mononuclear cells(PBMCs)of patients with DVT were detected by flow cytometry,expressions of CD80 and CD86 mRNA were detected by qRT-PCR,Western blot was used to detect protein levels of JAK2,STAT3 and phosphory-lation(p-JAK2 and p-STAT3)in PBMC of DVT patients and mice.LPS-induced mouse DC2.4 cells were treated with XSTMD drug-containing serum.Western blot was used to determine the protein levels of JAK2,STAT3,p-JAK2 and p-STAT3.ELISA was used to detect protein levels of IL-6,TNF-α,IL-10 and TGF-β1 in cell culture supernatant.Results:After treatment with XSTMD,weight and length of thrombus were significantly reduced in mice with DVT(P<0.001).Compared with before treatment,expressions of FGB and D2D were significantly decreased in plasma of DVT patients(P<0.001),proportion of pDC was significantly increased,while pro-portion of cDC was significantly decreased in PBMC of DVT patients(P<0.01),expression of HLA-DR protein and mRNA levels of CD80 and CD86 were significantly decreased in PBMC of DVT patients(P<0.05,P<0.01,P<0.001)after treatment with XSTMD.Levels of p-JAK2 and p-STAT3 protein were significantly increased in PBMC from DVT patients and mice treated with XSTMD(P<0.05).After treatment with serum containing XSTMD,protein levels of p-JAK2 and p-STAT3 induced by LPS were significantly increased in murine DC2.4 cells(P<0.05).Protein expressions of IL-6 and TNF-α were significantly decreased,while protein expressions of IL-10 and TGF-β1 were significantly increased in cell supernatant(P<0.01,P<0.001).Conclusion:XSTMD effectively treats DVT by pre-cisely regulating the JAK2/STAT3 signaling pathway to promote the differentiation of DCs into pDC and alleviate inflammatory injury.

Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

[Purpose]To analyze the trends of mortality and probability of premature mortality caused by colorectal cancer in Jinshan District of Shanghai from 1980 to 2023.[Methods]The death database of Jinshan District from 1980 to 2023 were established based on the death reports from the medical institutions and public security bureau at all levels.The crude mortality rate,age-standardized mortality rate by Chinese standard population and world standard population(ASRC and ASRW),age-specific mortality rate,probability of premature mortality,annual percentage change(APC)and average annual percentage change(AAPC)of colorectal cancer were calculated.[Results]The crude mortality rate of colorectal cancer increased from 1980 to 2023(AAPC=2.36％,P＜0.001)and the ASRW of colorectal cancer decreased at the same period(AAPC=-1.02％,P=0.003).The ASRW of colorectal cancer in male and female showed a decreasing trend from 1990 to 1999(APC=-5.08％,-7.85％,P=0.007,0.011),but there was no significant change in other periods.The age-specific mortality rate increased with age and reached the peak at the age group of 70～74 years old during 1980-1989,75～79 years old during 1990-1999,80～84 years old during 2000-2009 and 2010-2019,85 years old and above during 2020-2023(109.22/105,77.56/105,113.78/105,172.82/105 and 236.58/105,respectively).The probability of premature mortality of colorectal cancer decreased in male and female(AAPC=-1.10％,-2.41％,P=0.047,＜0.001),but there was no change after the year of 2000.[Conclusion]The overall mortality rate of colorectal cancer in Jinshan District showed a decreasing trend from 1980 to 2023,but the standardized mortality rate and the probability of premature mortality had not shown a significant downward trend since 2000.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Objective:To investigate the molecular mechanism of Xiaoshuantongmai Decoction(XSTMD)targeting JAK2/STAT3 signaling pathway to regulate the function of dendritic cells(DCs)in treatment of deep vein thrombosis(DVT).Methods:After treatment of DVT with XSTMD,expressions of fibrinogen beta chain(FGB)and D-dimer(D2D)protein in plasma of patients with DVT were detected by ELISA,proportion of plasmacytoid dendritic cell(pDC)and conventional dendritic cell(cDC),and expression of HLA-DR protein in peripheral blood mononuclear cells(PBMCs)of patients with DVT were detected by flow cytometry,expressions of CD80 and CD86 mRNA were detected by qRT-PCR,Western blot was used to detect protein levels of JAK2,STAT3 and phosphory-lation(p-JAK2 and p-STAT3)in PBMC of DVT patients and mice.LPS-induced mouse DC2.4 cells were treated with XSTMD drug-containing serum.Western blot was used to determine the protein levels of JAK2,STAT3,p-JAK2 and p-STAT3.ELISA was used to detect protein levels of IL-6,TNF-α,IL-10 and TGF-β1 in cell culture supernatant.Results:After treatment with XSTMD,weight and length of thrombus were significantly reduced in mice with DVT(P<0.001).Compared with before treatment,expressions of FGB and D2D were significantly decreased in plasma of DVT patients(P<0.001),proportion of pDC was significantly increased,while pro-portion of cDC was significantly decreased in PBMC of DVT patients(P<0.01),expression of HLA-DR protein and mRNA levels of CD80 and CD86 were significantly decreased in PBMC of DVT patients(P<0.05,P<0.01,P<0.001)after treatment with XSTMD.Levels of p-JAK2 and p-STAT3 protein were significantly increased in PBMC from DVT patients and mice treated with XSTMD(P<0.05).After treatment with serum containing XSTMD,protein levels of p-JAK2 and p-STAT3 induced by LPS were significantly increased in murine DC2.4 cells(P<0.05).Protein expressions of IL-6 and TNF-α were significantly decreased,while protein expressions of IL-10 and TGF-β1 were significantly increased in cell supernatant(P<0.01,P<0.001).Conclusion:XSTMD effectively treats DVT by pre-cisely regulating the JAK2/STAT3 signaling pathway to promote the differentiation of DCs into pDC and alleviate inflammatory injury.

Objective:To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria.Methods:It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups.Results:A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test ( χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions:Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

Objective:To investigate the feasibility of construction of rat models of psoriasis-like lesions by using interleukin (IL) -23/T-helper 17 (Th17) axis-related cytokines combined with imiquimod.Methods:A total of 110 Wistar rats were randomly divided into normal control group, imiquimod alone group, imiquimod combined with interferon (IFN) -α2a (180 000, 60 000, 20 000 IU/kg) groups, imiquimod combined with tumor necrosis factor (TNF) -α (45 000, 15 000, 5 000 IU/kg) groups, and imiquimod combined with IL-2 (90 000, 30 000, 10 000 IU/kg) groups, and there were 10 rats in each group. After hair removal from the central area (2 cm × 2 cm) of the rat back, rats in the imiquimod alone group were topically treated with imiquimod 5% cream at a dose of 20 mg/cm 2 on the shaved back; rats in the imiquimod combined with different cytokine groups were treated with topical imiquimod 5% cream at the same dose on the shaved back for 15 minutes followed by intraperitoneal injections of cytokines at corresponding doses once a day for 10 consecutive days. During the treatment, skin lesions on the rat back were evaluated by using the psoriasis area and severity index (PASI) scores every day. On day 10, serum samples were collected from the rats after anesthesia, and enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of IL-17A, TNF-α, IL-23, IFN-α and IL-1β in the serum samples in each group; then, the rats were sacrificed, lesional skin tissues on the rat back were taken for histopathological examinations and evaluated by Baker scores; an immunohistochemical study was conducted to determine the expression of CD4 and CD8 in some skin lesions. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference (LSD) - t test for multiple comparisons; for data with heterogeneous variance, the Kruskal-Wallis H test was used. Results:On day 3 after molding, the rats in the imiquimod alone group and combination groups gradually presented with psoriasis-like skin manifestations, such as erythema, scales and epidermal thickening; the PASI scores reached a peak on day 7 in the imiquimod alone group, and on day 6 in the combination groups. On day 10, histopathological examination of the skin lesions in the imiquimod alone group and combination groups both showed different psoriasis-like pathological features, such as hyperkeratosis, parakeratosis, acanthosis, thinning or disappearance of the granular layer. There were significant differences in the PASI scores and Baker scores among the normal control group, imiquimod alone group and combination groups ( H = 43.33, F = 42.15, both P < 0.001). The PASI scores were higher in the imiquimod combined with IFN-α2a (180 000 IU/kg) group and the imiquimod combined with IL-2 (90 000 IU/kg) group (9.4 ± 1.1, 8.8 ± 0.6, respectively) than in the imiquimod alone group (7.5 ± 1.1, P = 0.002, 0.030 respectively) ; the Baker scores were higher in the imiquimod combined with IFN-α2a (180 000, 60 000 IU/kg) groups, the imiquimod combined with TNF-α (45 000 IU/kg) group, and the imiquimod combined with IL-2 (90 000 IU/kg) group than in the imiquimod alone group (all P < 0.05). The serum levels of TNF-α, IL-17A, IL-1 β and IL-23 significantly differed among groups ( F = 128.97, F = 6.90, H = 27.45, H = 21.10, all P < 0.05). Compared with the imiquimod alone group, the IL-17A level significantly increased in the imiquimod combined with IL-2 (30 000 IU/kg) group (5.54 ± 1.78 pg/ml vs. 4.20 ± 1.14 pg/ml, P = 0.009), and the IL-23 level significantly increased in the imiquimod combined with IL-2 (90 000 IU/kg) group (37.89 ± 32.85 pg/ml vs. 8.56 ± 6.08 pg/ml, P = 0.036). Immunohistochemical study showed significant differences in the expression of CD4 and CD8 in skin lesions among all groups ( F = 7.21, H = 18.32, both P < 0.001), and the expression of CD4 and CD8 in skin lesions was significantly higher in the imiquimod combined with IL-2 (90 000 IU/kg) group than in the imiquimod alone group ( t = -2.46, -2.32, respectively, both P < 0.05) . Conclusion:Imiquimod combined with IFN-α2a or IL-2 could promote the occurrence of psoriasis-like skin lesions in rats, aggravate the development of psoriasis and prolong the maintenance time of the rat models.

Objective:To summarize the effect of reverse homodigital dorsal thumb flap in repairing thumb pulp defect.Methods:A retrospective case series study was conducted to analyze the clinical data of patients with thumb pulp defects admitted to the People's Hospital of Renqiu from March 2010 to June 2020. The dorsal homodigital island flap of the proximal phalanx was designed and harvested. During the procedure, the proximal digital artery of the perforator vessels of the flap was cut off and ligated. The digital artery pedicled flap was retrograde transferred to cover the thumb pulp defect. 9-0 line was used to anastomose the dorsal digital nerve with the proper digital nerve. The donor site was repaired with a free skin graft.Results:A total of 68 cases of thumb pulp defects were enrolled, all of whom were accompanied by exposure of the tendon of the distal phalanx. There were 39 males and 29 females, aged from 18 to 63 years (average of 35.8 years). The size of the proximal dorsal island flap was 2.0 cm × 3.0 cm to 3.1 cm × 4.2 cm. All flaps and skin grafts survived, and wounds healed primarily. All patients were followed up for 6 to 28 months (mean, 10.6 months). The color, texture, and contour of the flaps were good. All repaired thumbs got the normal function of extension and flexion. At the last follow-up, the two-point discrimination of flaps was 4-11 mm.Conclusions:It has the advantages of small trauma, simple operation, and good curative effect, using the homodigital dorsal thumb flap to repair the thumb pulp defect.