Objective To evaluate the safety of the 13-valent pneumococcal polysaccharide conjugate vaccine (tetanus toxoid/diphtheria toxoid) (PCV13-TT/DT) among age-eligible children in Tianjin through a combination of active and passive surveillance methods. Methods From July 15, 2023, to August 31, 2024, active surveillance for adverse events following immunization (AEFI) was conducted among recipients of PCV13-TT/DT at 18 selected vaccination clinics in Tianjin. Recipients were monitored through on-site observation or telephone follow-up within 30 minutes after vaccination and on days 1, 3, 7, and 28. Passive surveillance for AEFI was conducted among recipients of PCV13-TT/DT at other vaccination clinics across the city. The incidence of AEFI was analyzed using descriptive epidemiological methods. Results A total of 24 916 recipients of PCV13-TT/DT were observed, with 440 AEFI cases reported, resulting in an overall incidence rate of 176.59 per 10 000. The incidence rate of AEFI in active surveillance was 813.79 per 10 000, significantly higher than that in passive surveillance (20.49 per 10 000; P< 0.001). The incidence rates of general reactions, abnormal reactions, and coincidental cases in active surveillance were 744.44 per 10 000, 8.16 per 10 000, and 61.19 per 10 000, respectively, all of which were higher than those in passive surveillance (18.49 per 10 000, 0.50 per 10 000, and 1.50 per 10 000), with P values < 0.05. General reactions were mainly characterized by fever, local redness, and local induration. Abnormal reactions included angioedema and allergic rash. Coincidental cases were mainly infections. No severe adverse reactions occurred. Conclusion The large-scale vaccination of PCV13-TT/DT after its launch has good safety, and continuous strengthening of vaccine safety monitoring is needed.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

Objective To explore the mechanism of Scutellaria baicalensis(Huangqin)in ameliorating postoperative cognitive dysfunction in surgical patients through network pharmacology approaches combined with experimental validation.Methods Network pharmacology was used to screen the relevant targets and pathways of Huangqin in relation to postoperative cognitive dysfunction,followed by molecular docking to verify the affinity of core components with key targets.HT22 cell line of mouse hippocampal neurons was cultured,and an inflammation injury model was induced by LPS stimulation.Huangqin was selected for intervention treatment,divided into five groups:control group,model group,low-dose Huangqin group(10 μmol/L),medium-dose Huangqin group(50 μmol/L),and high-dose Huangqin group(100 μmol/L).After co-culturing for 24 h,the expression of key target proteins HIF1A,MAPK1(ERK2/p-ERK2),and SIRT1 were detected by Western blotting,and the mRNA expression of these proteins was measured by qRT-PCR.Results A total of 27 active components of Huangqin were screened by network pharmacology,corresponding to 379 targets,with 220 disease targets related to POCD,resulting in 35 intersecting genes.Molecular docking results showed that components like baicalein and oroxylin A had strong affinity with targets such as HIF1A,MAPK1,and SIRT1.In vitro experimental results indicated that baicalein significantly downregulated the expression and transcription levels of HIF1A and MAPK1(ERK2/p-ERK2),while upregulating the expression and transcription levels of SIRT1,effectively improved the inflammatory response in HT22 cells and reduced neuronal damage.Conclusion The traditional Chinese medicine Huangqin can reduce the occurrence and development of postoperative cognitive dysfunction by improving the expression of key proteins,controlling inflammatory responses,and protecting neuronal function.

Objective:To explore the clinical efficacy and safety of endoscopic rubber band ligation (ERBL) and endoscopic injection sclerotherapy (EIS) in the treatment of grade I-III internal hemorrhoids, to provide a basis for the individualized treatment of patients with internal hemorrhoids in clinical practice.Methods:A retrospective cohort study was conducted. A total of 613 patients with grade I to III internal hemorrhoids who underwent ERBL or EIS at The Sixth Affiliated Hospital of Sun Yat-sen University from December 2019 to November 2023 were retrospectively collected. Inclusion criteria: (1) Patients diagnosed with symptomatic grade I-III internal hemorrhoids who failed conservative treatments such as diet adjustment and medication; (2) Patients who were unable or unwilling to receive surgical treatment due to multiple underlying systemic diseases. Exclusion criteria: (1) Patients with grade I-III internal hemorrhoids complicated with incarceration, thrombosis or other complications; (2) Patients with a history of hemorrhoid surgery; (3) Patients complicated with perianal abscess, anal fistula, active proctitis, rectal tumor, polyp, radiation proctitis or inflammatory bowel disease; (4) Patients with incomplete clinical data or lost to follow-up. This study was divided into the ERBL group and the EIS group based on different treatment. Baseline characteristics, postoperative effective rate, recurrence rate, pain score, anal distension, anal edema, complication rate, and treatment satisfaction were compared between the two groups.Results:After balancing with propensity score matching (PSM), a total of 313 patients were included, including 200 in the ERBL group and 113 in the EIS group. There were no statistically significant differences in baseline characteristics, such as gender, age, body mass index, Goligher classification, and laboratory test indicators, between the two groups (all P > 0.05), indicating that the two groups were comparable. The cure rates of the ERBL group and the EIS group were 64.0% (128/200) and 62.8% (71/113), respectively. The marked effective rates were 31.5% (63/200) and 34.5% (39/113), and the ineffective rates were 4.5% (9/200) and 2.7% (3/113), respectively. Statistical analysis revealed no statistically significant difference in efficacy between the two groups within 3 months after the operation (χ2=0.858, P=0.651). The recurrence rate of the ERBL group was lower than that of the EIS group [13.1% (25/191) vs. 18.2% (20/110)], but the difference was not statistically significant (χ2=1.424, P=0.233). Subgroup analysis showed that the recurrence rates of ERBL and EIS were similar in grade I-II internal hemorrhoids [10.3% (15/146) vs. 10.5% (9/86), χ2=0.002, P=0.963]; in grade III internal hemorrhoids, the recurrence rate of the ERBL group was lower than that of the EIS group [22.2% (10/45) vs. 45.8% (11/24), χ2=4.121, P=0.042]. Still, the difference was not statistically significant after Bonferroni correction (χ2=4.121, corrected P>0.025). Compared with the ERBL group, the EIS group had a lower pain score on the first day after operation [0 (0, 0) vs. 1 (0, 3), Z=-8.211, P<0.001] and a lower incidence of anal distension [25.7% (29/113) vs. 61.5% (123/200), χ2=37.122, P<0.001], with statistically significant differences. The total incidence of complications in the ERBL group was significantly higher than that in the EIS group [29.5% (59/200) vs. 4.4% (5/113), χ2=27.910, P<0.001], mainly reflected in postoperative bleeding [18.0% (36/200) vs. 3.5% (4/113), χ2=13.544, P<0.001] and urinary retention [8.5% (17/200) vs. 0, χ2=10.157, P=0.001], with statistically significant differences. There were no statistically significant differences in postoperative satisfaction, health status score, and the proportion of returning to everyday life within 1 month between the two groups (all P>0.05). Conclusions:Both ERBL and EIS are effective minimally invasive therapies for grade I-III internal hemorrhoids. EIS is preferred for grade I and II internal hemorrhoids to reduce complications, while ERBL shows a trend in reducing the recurrence rate of grade III internal hemorrhoids. Clinical decisions should be made comprehensively based on the classification, patient tolerance, and prognosis.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

Objective To explore the mechanism of Scutellaria baicalensis(Huangqin)in ameliorating postoperative cognitive dysfunction in surgical patients through network pharmacology approaches combined with experimental validation.Methods Network pharmacology was used to screen the relevant targets and pathways of Huangqin in relation to postoperative cognitive dysfunction,followed by molecular docking to verify the affinity of core components with key targets.HT22 cell line of mouse hippocampal neurons was cultured,and an inflammation injury model was induced by LPS stimulation.Huangqin was selected for intervention treatment,divided into five groups:control group,model group,low-dose Huangqin group(10 μmol/L),medium-dose Huangqin group(50 μmol/L),and high-dose Huangqin group(100 μmol/L).After co-culturing for 24 h,the expression of key target proteins HIF1A,MAPK1(ERK2/p-ERK2),and SIRT1 were detected by Western blotting,and the mRNA expression of these proteins was measured by qRT-PCR.Results A total of 27 active components of Huangqin were screened by network pharmacology,corresponding to 379 targets,with 220 disease targets related to POCD,resulting in 35 intersecting genes.Molecular docking results showed that components like baicalein and oroxylin A had strong affinity with targets such as HIF1A,MAPK1,and SIRT1.In vitro experimental results indicated that baicalein significantly downregulated the expression and transcription levels of HIF1A and MAPK1(ERK2/p-ERK2),while upregulating the expression and transcription levels of SIRT1,effectively improved the inflammatory response in HT22 cells and reduced neuronal damage.Conclusion The traditional Chinese medicine Huangqin can reduce the occurrence and development of postoperative cognitive dysfunction by improving the expression of key proteins,controlling inflammatory responses,and protecting neuronal function.

Objective:To explore the clinical efficacy and safety of endoscopic rubber band ligation (ERBL) and endoscopic injection sclerotherapy (EIS) in the treatment of grade I-III internal hemorrhoids, to provide a basis for the individualized treatment of patients with internal hemorrhoids in clinical practice.Methods:A retrospective cohort study was conducted. A total of 613 patients with grade I to III internal hemorrhoids who underwent ERBL or EIS at The Sixth Affiliated Hospital of Sun Yat-sen University from December 2019 to November 2023 were retrospectively collected. Inclusion criteria: (1) Patients diagnosed with symptomatic grade I-III internal hemorrhoids who failed conservative treatments such as diet adjustment and medication; (2) Patients who were unable or unwilling to receive surgical treatment due to multiple underlying systemic diseases. Exclusion criteria: (1) Patients with grade I-III internal hemorrhoids complicated with incarceration, thrombosis or other complications; (2) Patients with a history of hemorrhoid surgery; (3) Patients complicated with perianal abscess, anal fistula, active proctitis, rectal tumor, polyp, radiation proctitis or inflammatory bowel disease; (4) Patients with incomplete clinical data or lost to follow-up. This study was divided into the ERBL group and the EIS group based on different treatment. Baseline characteristics, postoperative effective rate, recurrence rate, pain score, anal distension, anal edema, complication rate, and treatment satisfaction were compared between the two groups.Results:After balancing with propensity score matching (PSM), a total of 313 patients were included, including 200 in the ERBL group and 113 in the EIS group. There were no statistically significant differences in baseline characteristics, such as gender, age, body mass index, Goligher classification, and laboratory test indicators, between the two groups (all P > 0.05), indicating that the two groups were comparable. The cure rates of the ERBL group and the EIS group were 64.0% (128/200) and 62.8% (71/113), respectively. The marked effective rates were 31.5% (63/200) and 34.5% (39/113), and the ineffective rates were 4.5% (9/200) and 2.7% (3/113), respectively. Statistical analysis revealed no statistically significant difference in efficacy between the two groups within 3 months after the operation (χ2=0.858, P=0.651). The recurrence rate of the ERBL group was lower than that of the EIS group [13.1% (25/191) vs. 18.2% (20/110)], but the difference was not statistically significant (χ2=1.424, P=0.233). Subgroup analysis showed that the recurrence rates of ERBL and EIS were similar in grade I-II internal hemorrhoids [10.3% (15/146) vs. 10.5% (9/86), χ2=0.002, P=0.963]; in grade III internal hemorrhoids, the recurrence rate of the ERBL group was lower than that of the EIS group [22.2% (10/45) vs. 45.8% (11/24), χ2=4.121, P=0.042]. Still, the difference was not statistically significant after Bonferroni correction (χ2=4.121, corrected P>0.025). Compared with the ERBL group, the EIS group had a lower pain score on the first day after operation [0 (0, 0) vs. 1 (0, 3), Z=-8.211, P<0.001] and a lower incidence of anal distension [25.7% (29/113) vs. 61.5% (123/200), χ2=37.122, P<0.001], with statistically significant differences. The total incidence of complications in the ERBL group was significantly higher than that in the EIS group [29.5% (59/200) vs. 4.4% (5/113), χ2=27.910, P<0.001], mainly reflected in postoperative bleeding [18.0% (36/200) vs. 3.5% (4/113), χ2=13.544, P<0.001] and urinary retention [8.5% (17/200) vs. 0, χ2=10.157, P=0.001], with statistically significant differences. There were no statistically significant differences in postoperative satisfaction, health status score, and the proportion of returning to everyday life within 1 month between the two groups (all P>0.05). Conclusions:Both ERBL and EIS are effective minimally invasive therapies for grade I-III internal hemorrhoids. EIS is preferred for grade I and II internal hemorrhoids to reduce complications, while ERBL shows a trend in reducing the recurrence rate of grade III internal hemorrhoids. Clinical decisions should be made comprehensively based on the classification, patient tolerance, and prognosis.