Functional dyspepsia （FD） is a prioritized disease category where traditional Chinese medicine （TCM） demonstrates distinct therapeutic advantages. The current western medicine treatment for FD is mainly based on proton pump inhibitors and prokinetic agents， with digestive enzymes， probiotics and antidepressants serving as adjuvant medication， yet such therapies still have certain limitations. TCM treatment for FD includes oral administration of Chinese herbal formulas and Chinese patent medicines， as well as external TCM therapies such as acupuncture and moxibustion， acupoint application， hot medicinal compress therapy， rubbing with ointment， medicinal iontophoresis， auricular acupoint therapy and tui na （Chinese medical massage）. The combined treatment of FD with integrated TCM and western medicine can significantly improve clinical effectiveness and reduce adverse reactions. The common mechanisms underlying the therapeutic effects of both TCM and western medicine revolve around the core pathological processes of FD， mainly focusing on restoring gastrointestinal motility， regulating the levels of brain-gut peptides， modulating intestinal microecology， and ameliorating inflammatory status. The differential mechanisms lie in the precise targeting feature of western medicine versus the holistic-regulating and multi-target characteristics of TCM， and the two approaches exert a synergistic effect to enhance efficacy. This paper proposes to leverage the advantages of TCM in holistic regulation and the strengths of western medicine in targeted treatment， so as to provide personalized and comprehensive treatment regimens for FD patients.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Objective:To compare the accuracy and applicability of three adult height prediction methods based on artificial intelligence-assisted bone age assessment—the Bayley-Pinneau method(BP method), the Tanner-Whitehouse 3 method(TW3 method), and China 05 method—in girls.Methods:This bidirectional cohort study collected clinical data and 690 posteroanterior X-ray images of the left hand from 278 female children who underwent pubertal development assessments at Shenzhen Children′s Hospital between January 2014 and December 2020, with follow-up until adult height was reached. Adult height prediction was performed using BP, TW3, and China 05 methods on artificial intelligence-assisted bone age assessment.Results:The BP and TW3 methods overestimated adult height by(1.7±3.7) cm and(2.6±3.0) cm, respectively, while the China 05 method underestimated adult height by(2.3±3.5) cm. The proportion of PAH within±5 cm of FAH were 80.0% for the TW3 method, 77.0% for the BP method, and 74.2% for the China 05 method, with significant differences among them( P=0.038). Analysis of cases with prediction deviations>10 cm and subgroup comparisons revealed that the TW3 and BP methods were more likely to overestimate adult height in girls aged 6.0-<8.0 years, with delayed bone age, or in the prepubertal stage(all P<0.001). The China 05 method was more prone to underestimate adult height in those with advanced bone age( P<0.001). All three methods showed significantly greater prediction errors(absolute difference between PAH and FAH) in girls with early puberty compared to those with normal pubertal development(all P<0.05). Conclusions:The TW3 and BP methods tend to overestimate adult height in girls, while the China 05 method tends to underestimate it. Caution is warranted when predicting adult height, particularly in girls under 8 years of bone age, with delayed or advanced bone age, and those with early puberty.

Objective:To investigate the relationship between postpartum hemorrhage (PPH) volume and the risk of adverse clinical outcomes in pregnant women.Methods:This was a retrospective cohort study of 41 494 deliveries at Peking University Third Hospital from 2012 to 2020. With PPH volume as the main exposure, the outcome indicators included: (1) Severe adverse outcomes: shock or embolism, abnormal coagulation function, abnormal liver function, and kidney injury; (2) General adverse outcomes: moderate to severe anemia, hypoalbuminemia, postpartum blood transfusion. Robust Poisson regression was employed to calculate the risk of each outcome index in pregnant women with different PPH volumes under the condition of controlling confounding factors, and to analyze the risk trends of each outcome index with the change of PPH volumes.Results:A total of 41 494 pregnant women were included in the study, including 9 959 cases (24.00%, 9 959/41 494), 23 974 cases (57.78%, 23 974/41 494), 5 235 cases (12.62%, 5 235/41 494), 1 144 cases (2.76%, 1 144/41 494), 508 cases (1.22%, 508/41 494), 208 cases (0.50%, 208/41 494), 207 cases (0.50%, 207/41 494) and 259 cases (0.62%, 259/41 494) pregnant women with PPH volume <250, 250-499, 500-749, 750-999, 1 000-1 249, 1 250-1 499, 1 500-1 999 and ≥2 000 ml, respectively. The risk of any serious adverse outcome, such as shock or embolism, abnormal coagulation function, abnormal liver function and kidney injury, showed a "J-shaped" relationship with PPH volume: risks remained stable (0.26%-0.59%) below 1 500 ml but increased significantly to 3.38% ( RR=3.43, 95% CI: 1.14-10.35) at 1 500-1 999 ml and 5.02% ( RR=4.53, 95% CI: 1.49-13.75) at ≥2 000 ml (all P<0.05). Moderate-to-severe anemia showed threshold effects at 750 ml ( RR ranging from 7.21 to 8.53) and hypoalbuminemia at 1 250 ml ( RR ranging from 3.24 to 3.83), with risks plateauing beyond these thresholds (all P<0.05). Conclusion:It is suggested that 750 ml, 1 250 ml and 1 500 ml should be used as the key intervention thresholds, corresponding to the initiation thresholds of anemia, hypoalbuminemia management and multidisciplinary intensive care, respectively, so as to provide a new reference for optimizing the clinical diagnosis and treatment strategy of PPH.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Objective:To investigate the relationship between postpartum hemorrhage (PPH) volume and the risk of adverse clinical outcomes in pregnant women.Methods:This was a retrospective cohort study of 41 494 deliveries at Peking University Third Hospital from 2012 to 2020. With PPH volume as the main exposure, the outcome indicators included: (1) Severe adverse outcomes: shock or embolism, abnormal coagulation function, abnormal liver function, and kidney injury; (2) General adverse outcomes: moderate to severe anemia, hypoalbuminemia, postpartum blood transfusion. Robust Poisson regression was employed to calculate the risk of each outcome index in pregnant women with different PPH volumes under the condition of controlling confounding factors, and to analyze the risk trends of each outcome index with the change of PPH volumes.Results:A total of 41 494 pregnant women were included in the study, including 9 959 cases (24.00%, 9 959/41 494), 23 974 cases (57.78%, 23 974/41 494), 5 235 cases (12.62%, 5 235/41 494), 1 144 cases (2.76%, 1 144/41 494), 508 cases (1.22%, 508/41 494), 208 cases (0.50%, 208/41 494), 207 cases (0.50%, 207/41 494) and 259 cases (0.62%, 259/41 494) pregnant women with PPH volume <250, 250-499, 500-749, 750-999, 1 000-1 249, 1 250-1 499, 1 500-1 999 and ≥2 000 ml, respectively. The risk of any serious adverse outcome, such as shock or embolism, abnormal coagulation function, abnormal liver function and kidney injury, showed a "J-shaped" relationship with PPH volume: risks remained stable (0.26%-0.59%) below 1 500 ml but increased significantly to 3.38% ( RR=3.43, 95% CI: 1.14-10.35) at 1 500-1 999 ml and 5.02% ( RR=4.53, 95% CI: 1.49-13.75) at ≥2 000 ml (all P<0.05). Moderate-to-severe anemia showed threshold effects at 750 ml ( RR ranging from 7.21 to 8.53) and hypoalbuminemia at 1 250 ml ( RR ranging from 3.24 to 3.83), with risks plateauing beyond these thresholds (all P<0.05). Conclusion:It is suggested that 750 ml, 1 250 ml and 1 500 ml should be used as the key intervention thresholds, corresponding to the initiation thresholds of anemia, hypoalbuminemia management and multidisciplinary intensive care, respectively, so as to provide a new reference for optimizing the clinical diagnosis and treatment strategy of PPH.

Objective:To compare the accuracy and applicability of three adult height prediction methods based on artificial intelligence-assisted bone age assessment—the Bayley-Pinneau method(BP method), the Tanner-Whitehouse 3 method(TW3 method), and China 05 method—in girls.Methods:This bidirectional cohort study collected clinical data and 690 posteroanterior X-ray images of the left hand from 278 female children who underwent pubertal development assessments at Shenzhen Children′s Hospital between January 2014 and December 2020, with follow-up until adult height was reached. Adult height prediction was performed using BP, TW3, and China 05 methods on artificial intelligence-assisted bone age assessment.Results:The BP and TW3 methods overestimated adult height by(1.7±3.7) cm and(2.6±3.0) cm, respectively, while the China 05 method underestimated adult height by(2.3±3.5) cm. The proportion of PAH within±5 cm of FAH were 80.0% for the TW3 method, 77.0% for the BP method, and 74.2% for the China 05 method, with significant differences among them( P=0.038). Analysis of cases with prediction deviations>10 cm and subgroup comparisons revealed that the TW3 and BP methods were more likely to overestimate adult height in girls aged 6.0-<8.0 years, with delayed bone age, or in the prepubertal stage(all P<0.001). The China 05 method was more prone to underestimate adult height in those with advanced bone age( P<0.001). All three methods showed significantly greater prediction errors(absolute difference between PAH and FAH) in girls with early puberty compared to those with normal pubertal development(all P<0.05). Conclusions:The TW3 and BP methods tend to overestimate adult height in girls, while the China 05 method tends to underestimate it. Caution is warranted when predicting adult height, particularly in girls under 8 years of bone age, with delayed or advanced bone age, and those with early puberty.

During the process of dairy farming,various factors such as physical injury and bacterial infection act upon body tissues or organs,leading to the disruption of skin or mucous tissue integ-rity and subsequent tissue injury and trauma.The healing of these injuries is a complex process that necessitates the coordinated efforts of different cells and involvement of diverse cytokines.A-mong them,the interaction between macrophages and myofibroblasts is indispensable for efficient tissue repair.Nod-like receptor protein 3(NLRP3),a pattern recognition receptor in the innate im-mune system,may play a regulatory role in modulating this intricate process.In this study,cow myofibroblasts and M1 type bone marrow-derived macrophages were cultured in vitro,followed by collection of cell culture supernatant for co-culture analysis.Both cytokine secretion levels in M1 type bone marrow-derived macrophages as well as expression patterns levels of myofibroblast growth factor protein and mRNA were detected.The regulatory mechanism underlying NLRP3 in-volvement in mediating interactions between these two cell types was investigated using NLRP3 inhibitor MCC950.The results showed that an effective method for culturing cow muscle fibroblasts in vitro was successfully established and myofibroblast conditioned medium(MFbCM)could regulate M1 macrophage secretion profiles.Moreover,M1 macrophage conditioned medium(M1?CM)was found to influence myofibroblast growth factor expression levels.Our findings sug-gest that NLRP3 plays a significant regulatory role during crosstalk between myofibroblasts and M1-type pro-inflammatory macrophages.

Objective:To examine whether multiple-course prophylactic intravesical instillation chemotherapy is superior to single-course chemotherapy in preventing bladder tumor recurrence after radical nephroureterectomy(RNU)for primary upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the PubMed, Wanfang Data and China National Knowledge Infrastructure and all publications before March 2021 about clinical trials comparing the effects of single-course and multiple-course prophylactic intravesical instillation chemotherapy after RNU for UTUC were retrieved.Analysis was performed using Stata/SE 12.0.Results:Seven trials included a total of 998 patients, with 473 participants receiving multiple-course and 525 receiving single-course intravesical instillation chemotherapy.Bladder cancer recurrence occurred in 69 out of 473 patients(14.6%)with multiple-course chemotherapy and in 123 out of 525 patients(23.4%)with single-course chemotherapy.The absolute risk reduction was 8.8% and the relative risk reduction was 37.6%.Compared with a single-course instillation, the pooled OR of bladder cancer recurrence was 0.55(95% CI: 0.40-0.76, P<0.001)for multiple-course instillations.No serious adverse events were reported. Conclusions:Compared with single-course instillation chemotherapy, multiple-course prophylactic intravesical instillation chemotherapy significantly decreases the risk of bladder cancer recurrence in primary UTUC patients treated with RNU, indicating multiple intravesical instillation chemotherapy is superior to single instillation chemotherapy.

Objective:To explore the potential relationship of urethral pressure profilometry and the complications of artificial urethral sphincter (AUS) implantation.Methods:The clinical data of patients who underwent AUS implantation in Beijing Hospital from March 2019 to March 2022 were retrospectively analyzed. All the patients were male. The average course of disease was 43.1 months(ranging 11-120 months). The average age was (68.6±13.2) years. The median number of pads used was 4.5 (3.0, 6.0). The preoperative maximum urethral pressure (MUP) was (84.6±25.5) cmH 2O, and the maximum urethral closure pressure (MUCP) was 51.0 (41.0, 74.0) cmH 2O. AUS implantation was performed through a single perineal incision in all patients. The sleeve size was mainly determined by the measured urethral circumference of the patient. After installation of all components, the urethral pressure profilometry was performed under the state of device inactivation and activation. The pump was activated 6 weeks after the operation, and telephone follow-up was performed 3 months after the activation of the device. The urinary control and complications were recorded. The results of follow-up were compared with the results of urethral pressure profilometry, and the preliminary conclusions were drawn. Results:In this study, 3 patients (20%) received 4.0cm cuffs, 10 patients (66.7%) received 4.5cm cuffs, and 2 patients (13.3%) received 5.0cm cuffs. The MUP and MUCP of AUS device in inactivated state were (82.5±30.2) cmH 2O and 51.0(48.0, 77.0) cmH 2O. In the activated state, MUP was (138.9±21.7) cmH 2O and MUCP was 109.0(94.0, 133.0) cmH 2O. Compared with that before operation, the urethral pressure in the inactivated state did not increase significantly (all P > 0.05), while the urethral pressure in the activated state increased significantly (all P < 0.001). The patients were followed-up for 3-33 months. Thirteen patients (86.7%) used the initial installation device, and all of them met the standard of social continence. One patient died of cerebrovascular accident. One patient took out the device due to urethral erosion. The incidence of complications was 26.7% (4/15), including painless hematuria in 2 cases, scrotum and penis infection in 1 case, and urethral erosion in 1 case. The MUP and MUCP of these patients were (100.0 ± 40.7) cmH 2O and (80.8 ± 39.7) cmH 2O respectively. In the intraoperative active state, the MUP was (151.5 ± 15.3) cmH 2O and the MUCP was (123.0 ± 17.2) cmH 2O. The MUP of the other 3 patients in the device activation state was significantly higher than the average value, and all of them were above 150 cm H 2O, except one patient who was infected due to cognitive problems and chronic urinary retention. In 11 patients without complications, the MUP and MUCP were (76.1±24.7) cmH 2O and (55.1±20.0) cmH 2O respectively. In the intraoperative active state, the MUP was (134.4±22.5) cmH 2O and the MUCP was (108.5±29.8) cmH 2O. Conclusions:AUS implantation has a definite curative effect. Poor comprehension, and MUP higher than 150 cmH 2O in the activated state of the device may be risk factors for complications.