Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Objective:To assess the effect of short-term exposures to atmospheric fine particulate matter (PM 2.5) and its components on cognitive function in middle-aged and older people aged 40-89 and identify key components that affect cognitive function. Methods:From October 2018 to March 2019, a cross-sectional survey of middle-aged and older people aged 40-89 was conducted across 10 cities in Beijing-Tianjin-Hebei and neighboring regions of China. Data on PM 2.5 and its components were collected from the nearest air supermonitoring stations to the residential addresses. The cognitive function was assessed using the Min-Mental State Examination (MMSE) scale. Multiple linear regression models were used to assess the effect of short-term exposures to PM 2.5 and its components on cognitive function in middle-aged and older people. The restricted cubic spline function was used to fit the exposure-response relationship between different components and changes in MMSE scores. Results:The age of the 1 978 respondents was (65.1±13.4) years, and 976 (49.34%) were males. During the study period, the daily mean concentration of PM 2.5 was (71.2±43.2) μg/m 3, and the MMSE score was (28.2±3.7). The results of the multiple linear regression model showed that short-term exposures to PM 2.5 and its components were associated with cognitive decline in middle-aged and older people after adjusting for confounding factors, and the effect was higher at lag 0-28 days. For an interquartile range (64.3 μg/m 3) increase in PM 2.5 at lag 0-28 d, the MMSE score decreased by 5.91 (95% CI: 0.04, 11.77). For an interquartile range increase in organic carbon (OC), antimony (Sb), chromium (Cr), zinc (Zn), tin (Sn), and cadmium (Cd), the MMSE scores of middle-aged and older people decreased by 5.71 (95% CI: 1.69, 9.73), 4.67 (95% CI: 2.50, 6.84), 4.49 (95% CI: 1.05, 7.92), 3.65 (95% CI: 0.89, 6.42), 2.76 (95% CI: 1.22, 4.30), and 1.72 (95% CI: 0.53, 2.92). Conclusions:Short-term exposures to atmospheric PM 2.5 and its components (OC, Sb, Cr, Zn, Sn, and Cd) are associated with cognitive decline in middle-aged and older people.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Objective:To assess the effect of short-term exposures to atmospheric fine particulate matter (PM 2.5) and its components on cognitive function in middle-aged and older people aged 40-89 and identify key components that affect cognitive function. Methods:From October 2018 to March 2019, a cross-sectional survey of middle-aged and older people aged 40-89 was conducted across 10 cities in Beijing-Tianjin-Hebei and neighboring regions of China. Data on PM 2.5 and its components were collected from the nearest air supermonitoring stations to the residential addresses. The cognitive function was assessed using the Min-Mental State Examination (MMSE) scale. Multiple linear regression models were used to assess the effect of short-term exposures to PM 2.5 and its components on cognitive function in middle-aged and older people. The restricted cubic spline function was used to fit the exposure-response relationship between different components and changes in MMSE scores. Results:The age of the 1 978 respondents was (65.1±13.4) years, and 976 (49.34%) were males. During the study period, the daily mean concentration of PM 2.5 was (71.2±43.2) μg/m 3, and the MMSE score was (28.2±3.7). The results of the multiple linear regression model showed that short-term exposures to PM 2.5 and its components were associated with cognitive decline in middle-aged and older people after adjusting for confounding factors, and the effect was higher at lag 0-28 days. For an interquartile range (64.3 μg/m 3) increase in PM 2.5 at lag 0-28 d, the MMSE score decreased by 5.91 (95% CI: 0.04, 11.77). For an interquartile range increase in organic carbon (OC), antimony (Sb), chromium (Cr), zinc (Zn), tin (Sn), and cadmium (Cd), the MMSE scores of middle-aged and older people decreased by 5.71 (95% CI: 1.69, 9.73), 4.67 (95% CI: 2.50, 6.84), 4.49 (95% CI: 1.05, 7.92), 3.65 (95% CI: 0.89, 6.42), 2.76 (95% CI: 1.22, 4.30), and 1.72 (95% CI: 0.53, 2.92). Conclusions:Short-term exposures to atmospheric PM 2.5 and its components (OC, Sb, Cr, Zn, Sn, and Cd) are associated with cognitive decline in middle-aged and older people.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.