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.

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

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.

The over expression of p38-mitogen-activated protein kinase(MAPK)is considered a crucial pathway leading to myocardial fibrosis(MF)in the development of heart failure(HF).Traditional Chinese medicine active ingredients,compounds,and patent medicines have significant advantages in preventing and treating collagen accumulation,inhibiting the process of myocardial fibrosis,improving the degree of heart failure,and enhancing cardiac function by regulating p38-MAPK.This article summarizes recent research on traditional Chinese medicine's treatment of HF MF through the p38-MAPK signaling pathway with the aim to provide new potential targets for preventing and treating HF MF.

The over expression of p38-mitogen-activated protein kinase(MAPK)is considered a crucial pathway leading to myocardial fibrosis(MF)in the development of heart failure(HF).Traditional Chinese medicine active ingredients,compounds,and patent medicines have significant advantages in preventing and treating collagen accumulation,inhibiting the process of myocardial fibrosis,improving the degree of heart failure,and enhancing cardiac function by regulating p38-MAPK.This article summarizes recent research on traditional Chinese medicine's treatment of HF MF through the p38-MAPK signaling pathway with the aim to provide new potential targets for preventing and treating HF MF.

In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.
Acetic Acid ; Drugs, Chinese Herbal/analysis* ; Rhizome/chemistry* ; Quality Control ; Electronics

【Objective】 To investigate the penile appearance, sexual function, psychological status and related influencing factors of adult patients who underwent hypospadias repair surgery in their minors, so as to provide reference for the diagnosis, treatment and prognosis of hypospadias. 【Methods】 This study included 50 adult hypospadias patients who underwent urethroplasty in our hospital during May 2005 and Aug. 2018. The present appearance, sexual function and psychological status were evaluated. The correlation and consistency between hypospadias objective scoring evaluation (HOSE) and pediatric penile perception score (PPPS) were analyzed. Factors affecting the results were determined with univariate and multivariate regression analysis. 【Results】 The satisfaction rate of HOSE was significantly correlated with the urethral length and complications (P=0.024, P=0.033). The satisfaction rate of PPPS was significantly correlated with the number of urethral operations and postoperative complications (P=0.041, P=0.023). There was a weak correlation between HOSE and PPPS (r=0.291, P=0.040), but almost no consistency (Kappa=0.2, P=0.107). Sixty percent of the patients paid attention to the ventral appearance of penis, whose dissatisfaction rate of PPPS was higher than those who did not pay attention to the ventral appearance of the penis (19/30 vs. 6/20, P=0.021). Patients with multiple operations (>1), postoperative complications or unsatisfactory penile appearance were more likely to have inferiority complex (52.6% vs. 22.6%, P=0.029; 59.1% vs.14.3%, P=0.001;61.5% vs. 24.3%, P=0.015). Multivariate regression analysis showed that dissatisfaction with the appearance of the penis was an independent risk factor for patients’ perception of their own physical defects. Among the patients who believed that they had physical defects, the percentage of patients with grade IV penile erectile hardness was significantly lower than that of those who denied they had physical defects (9/17 vs. 27/33, P=0.047). 【Conclusion】 The undesirable postoperative penis appearance is likely to have a negative impact on patients’ long-term psychological state, which might further damage the sexual function in adulthood. Surgeons should pay attention to the penile appearance during the conduction of hypospadias repair.

Objective To explore the safety and efficiency of robot-assisted laparoscopic resection of pediatric adrenal region masses.Methods Six cases with adrenal region mass underwent robot-assisted laparoscopic adrenalectomy(RALA)from October 2019 to March 2022 in our hospital by using the da Vinci Robotic Surgery System.The patient was routinely placed in the 60°position on the healthy side.Two robotic arms were used to operate,and additional auxiliary operation holes were added as needed.The tumor was revealed by the combination of sharp and blunt separation,and the tumor trophoblastic vessels were identified.The tumor vessels were isolated by clamping with silk wire or biological clips.The tumor was fully freed and excised completely.Smaller specimens were removed by a slightly enlarged operation hole,and larger specimens were removed by another incision in the lower abdomen.Results All the 6 cases of procedures were successfully performed without conversion to open surgery.The operative duration was 90-240 min(mean,133.3 min),and the blood loss was 15-50 ml(mean,31.7 ml).In 2 cases,the drainage tube was not placed.In the remaining 4 cases,the indwelling time of the drainage tube after surgery was 4-8 d(mean,5.5 d).The postoperative hospital stay was5-15 d(mean,8.7 d).There were no complications except for one patient with postoperative bleeding.All the patients were followed up for 10-24 months(mean,16.7 months).CT examinations showed no recurrence of tumors.Conclusion Robotic-assisted laparoscopic resection of pediatric adrenal region masses is safe with satisfactory results.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective:To identify the transdermal constituents of Euodiae Fructus and predict its molecular mechanism in treating diarrhea by transdermal drug delivery. Method:Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and integrated pharmacology methods were used. The rapid identification of transdermal constituents of Euodiae Fructus was realized by the means of comparison of reference substances， analysis of UNIFI system and mass spectrometry. On this basis， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， SymMap， DisGeNET databases and literature were used to collected potential targets of transdermal constituents of Euodiae Fructus and targets for diarrhea-related diseases. The disease targets and drug targets were topologically analyzed to obtain the core targets， which were used for the Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Finally， Cytoscape 3.6.0 was used to build up a network of transdermal constituents-core targets-key pathways. Result:A total of 19 chemical constituents were speculatively identified from Euodiae Fructus extract， including quinolone alkaloids， limonins， indole alkaloids， organic acids and sterols. A total of 174 core targets of Euodiae Fructus for treating diarrhea were obtained by a topology analysis， signaling pathways of inflammatory response， cell proliferation， nutrient regulation and energy metabolism， signal transduction， bacterial infection were obtained through the analysis of KEGG enrichment. Conclusion:In this study， the transdermal constituents of Euodiae Fructus are identified for the first time， they can participate in the regulation of intestinal inflammation， maintain the integrity of intestinal mucosa， repaire and adjust the metabolism of the body by acting on Rac protein family， phosphatidylinositol 3-kinase， cytochrome P450 enzymes and aldo-keto reductase， respectively. In general， the molecular mechanism of Euodiae Fructus in the treatment of diarrhea is preliminarily elucidated.