Blood transcriptomics reveal systemic eosinophilic and neutrophilic inflammation patterns in patients with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal disease characterized by heterogeneous inflammation. However, the presence of systemic inflammation heterogeneity in CRSwNP patients remains unknown. This study aims to profile transcriptomic alterations in the blood of CRSwNP patients and characterize the CRSwNP heterogeneity based on blood transcriptomic biomarkers. METHODOLOGY: Patients with CRSwNP were prospectively recruited from three hospitals and chronologically divided into exploratory (n=123) and independent validation (n=46) cohorts. Transcriptomic profiles were generated by whole blood mRNA sequencing and subjected to patient clustering, differential expression, and pathway analysis. Differences in immune pattern and clinicopathologic features between clusters were assessed. A transcriptomic signature was defined and applied to an independent cohort to validate the findings. RESULTS: CRSwNP patients showed diverse blood transcriptomic profiles versus healthy controls, or when stratified by tissue and blood eosinophils and asthma comorbidity. Transcriptome-wide correlation analysis revealed a transcriptional signature associated with blood eosinophil levels, consisting of nine T2-related genes (CLC, SIGLEC8, ALOX15, IL5RA, PTGDR2, CCL23, CCR3, EPX and IL1RL1). Three distinct clusters with differing systemic eosinophilic and neutrophilic inflammation patterns and asthma comorbidity were identified based on transcriptomic profiling of T2 and T1/3-related blood biomarkers. A 36-gene signature was developed by machine learning and accurately predicted the three CRSwNP subtypes. Validation on an independent cohort confirmed the prediction robustness. CONCLUSIONS: There is heterogeneous systemic inflammation associated with eosinophilic and neutrophilic patterns in patients with CRSwNP. Endotyping based on blood transcriptomic biomarkers might lead to more personalized treatment strategies for CRSwNP in the future.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure.

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. DISCUSSION: Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF.

[Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 via upregulating hsa-miR-18b-5p].

OBJECTIVE: To explore the mechanism of tumor-associated fibroblasts (CAFs) for regulating proliferation and migration of prostate cancer (PCa) cells. METHODS: We conducted a bioinformatics analysis to identify miRNAs with high expression in PCa. The proliferation, migration and hsa-miR-18b-5p expression levels were observed in PCa cells co-cultured with CAFs. We further examined hsa-miR-18b-5p expression level in 20 pairs of PCa and adjacent tissue samples and in different PCa cell lines and normal epithelial cells using RT-qPCR. In PCa cell lines C4-2 and LNCAPNC, the effects of transfection with a hsa-miR-18b-5p inhibitor on cell proliferation, migration, invasion, drug resistance, apoptosis and cell cycle were evaluated, and the effects of has-miR-18b-5p knockdown on C4-2 cell xenograft growth and mouse survival were observed in nude mice. Dual luciferase reporter gene assay was used to validate the targeting relationship between hsa-miR-18b-5p and its target genes, whose expressions were detected in PCa cells using RT-qPCR and Western blotting. RESULTS: The expression of hsa-miR-18b-5p was significantly increased in the co-culture of CAFs and PCa cell lines, which exhibited significantly enhanced proliferation and migration abilities. Transfection with has-miR-18b-5p inhibitor strongly attenuated the effect of CAFs for promoting proliferation and migration of PCa cells, and in C4-2 and LNCAP cells cultured alone, inhibition of hsa-miR-18b-5p obviously suppressed cell proliferation, migration, invasion, and drug resistance. In the tumor-bearing mice, hsa-miR-18b-5p knockdown in the transplanted cells significantly inhibited xenograft growth and increased the survival time of the mice. Target gene prediction suggested that FBXL3 was a potential target of hsa-miR-18b-5p, and dual luciferase reporter gene confirmed a binding site between them. In C4-2 and LNCAP cells, hsa-miR-18b-5p knockdown resulted in significantly increased expression levels of FBXL3. CONCLUSION: CAFs promotes proliferation and migration of PCa cells by up-regulating hsa-miR-18b-5p to suppress FBXL3 expression.

[High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis].

OBJECTIVE: To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury (IRI) and its regulatory role in IRI. METHODS: C57BL/6 mice were divided into sham operation group, IRI (induced by clamping the renal artery) model group, IRI+DMSO treatment group, and IRI+SN-011 treatment group. Serum creatinine and blood urea nitrogen of the mice were analyzed, and pathological changes in the renal tissue were assessed with PAS staining. RT-qPCR, ELISA, Western blotting, and immunohistochemistry were used to detect the expression levels of STING, KIM-1, Bcl-2, Bax, caspase-3, TLR4, P65, NLRP3, caspase-1, CD68, MPO, IL-1ß, IL-6, and TNF-α in the renal tissues. In the cell experiment, HK-2 cells exposed to hypoxia-reoxygenation (H/R) were treated with DMSO or SN-011, and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR, Western blotting or flow cytometry. RESULTS: In C57BL/6 mice, renal IRI induced obvious renal tissue damage, elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1, STING, TLR4, P65, NLRP3, caspase-1, caspase-3, Bax, CD68, MPO, IL-1ß, IL-6, and TNF-α, and reduction of Bcl-2 expression level. Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes. In HK-2 cells, H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate, which was significantly lowered by treatment with SN-011. CONCLUSION: Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

TFCP2L1, a potential differentiation regulator, predicts favorable prognosis and dampens thyroid cancer progression.

PURPOSE: Thyroid cancer has an overwhelming incidence in the population. Thus, there is an urgent need to understand the underlying mechanism of its occurrence and development, which may provide new insights into therapeutic strategies. The role and mechanism of TFCP2L1 in regulating the progression of thyroid cancer remains unclear. METHODS: Public databases and clinical samples were used to detect the expression of TFCP2L1 in cancer and non-cancer tissues. Kaplan-Meier and Cox regression analyses were used to compare the differences in survival probability of the TFCP2L1 highly expressing group and the TFCP2L1 lowly expressing group. Functional assays were used to evaluate the biological effect of TFCP2L1 on thyroid cancer cells. RNA sequencing and enrichment analyses were used to find out pathways that were activated or inactivated by TFCP2L1. RESULTS: We demonstrated that TFCP2L1 was significantly downregulated in thyroid cancer. Decreased expression of TFCP2L1 was associated with malignant clinicopathological characteristics. Kaplan-Meier and Cox regression analyses indicated that thyroid tumor patients with low TFCP2L1 expression presented shorter disease-free interval and progression-free interval. Additionally, TFCP2L1 expression was positively correlated with thyroid differentiation degree. Overexpression of TFCP2L1 in thyroid cancer cells inhibited cell growth and motility in vitro, and tumorigenicity and metastasis in vivo. Mechanistically, the NF-κB signaling pathway was found inactivated by overexpressing TFCP2L1. CONCLUSION: Our results suggest that TFCP2L1 is a tumor suppressor and potential differentiation regulator, and might be a potential therapeutic target in thyroid cancer.

[Application effects of armor chest straps in patients with sternal dehiscence after repair surgery].

Objective: To investigate the application effects of armor chest straps in patients with sternal dehiscence after repair surgery. Methods: This study was a retrospective cohort study. The 11 patients who were admitted to the First Affiliated Hospital of Air Force Medical University (hereinafter referred to as the hospital) from March 2020 to March 2021 and used conventional chest straps after sternal dehiscence repair surgery were included in conventional chest strap group. The 12 patients who were admitted to the hospital from April 2021 to March 2022 and used armor chest straps after sternal dehiscence repair surgery were included in armor chest strap group. A special team for sternal dehiscence repair was set up, and the nurses in charge in the team instructed the patients in 2 groups on the correct abdominal breathing method, and the members of the surgical team performed the personalized surgery and wore the corresponding chest straps for the patients in 2 groups. The abdominal breathing frequency and chest breathing frequency on the first day after surgery were recorded. The pain intensity at 6, 24, 48, and 72 h after surgery was self-rated by the patients using numerical rating scale. The time of the first active cough and the time of wound healing after surgery were recorded. At postoperative suture removal, the cutting length of sutures induced by respiratory exercise was recorded. Whether there were complications such as redness, swelling, and exudation in flaps within 2 weeks after surgery were recorded, whether there were complications such as wound dehiscence or infection during follow-up of 3-12 months were recorded, and the incidence proportion of postoperative complications was calculated. At 6 months after surgery, the patients' scar status was evaluated by the Vancouver scar scale. Results: The abdominal breathing frequency of patients in armor chest strap group was (16.3±1.2) times/min on the first day after surgery, which was significantly higher than (5.3±1.4) times/min in conventional chest strap group (t=20.00, P<0.05), and the chest breath-ing frequency was (1.2±0.8) times/min, which was significantly lower than (12.4±1.5) times/min in conventional chest strap group (t=22.36, P<0.05). The pain intensity scores of patients in armor chest strap group at 6, 24, 48, and 72 h after surgery were significantly lower than those in conventional chest strap group (with t values of 15.07, 14.70, 13.66, and 11.03, respectively, P<0.05). The time of the first active cough and the time of wound healing after surgery of patients in armor chest strap group were significantly sooner than those in conventional chest strap group (with t values of 5.51 and 8.90, respectively, P<0.05). At postoperative suture removal, the cutting length of sutures induced by respiratory exercise of patients in conventional chest strap group was 2.0 (0, 5.0) mm, which was significantly longer than 2.0 (1.0, 2.0) mm in armor chest strap group (Z=4.10, P<0.05). There was no statistically significant difference in the incidence proportion of postoperative complications of patients between the 2 groups (P>0.05). At 6 months after surgery, the scar score of patients in armor chest strap group was 4.1±1.4, which was significantly lower than 5.6±1.4 in conventional chest strap group (t=2.71, P<0.05). Conclusions: The application of armor chest strap in patients with sternal dehiscence after repair surgery can increase the abdominal breathing frequency, reduce the wound cutting force, effectively relieve postoperative pain, increase the first active cough and wound healing speed, and alleviate postoperative scar proliferation, achieving good application effect.

[Clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand].

Objective: To explore the clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand. Methods: This study was a retrospective non-randomized controlled study. From February 2015 to February 2023, 24 patients (15 males and 9 females, aged 12-55 years) with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand, who met the inclusion criteria and were repaired with flap transplantation and tendon grafting or tendon anastomosis, were admitted to the First Affiliated Hospital of Air Force Medical University. According to different intervention time for postoperative rehabilitation treatment of patients, the patients were divided into conventional rehabilitation group and early rehabilitation group, with 12 cases in each group. Patients in early rehabilitation group received rehabilitation treatment immediately after surgery under the rehabilitation guidance of specialized rehabilitation physicians based on the characteristics of different postoperative periods. Patients in conventional rehabilitation group began rehabilitation treatment from the third week after surgery, and their rehabilitation treatment was the same as that of patients in early rehabilitation group from the second week after surgery. The patients in 2 groups were treated in the hospital until the sixth week after surgery. The occurrence of flap vascular crisis and tendon rupture were observed within 6 weeks after surgery. After 6 weeks of surgery, the manual muscle test was used to measure the pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, and grip force of the affected hand; the total action motion method was used to evaluate the finger joint range of motion of the affected hand, and the excellent and good ratio was calculated; the Carroll upper extremity function test was used to score and rate the function of the affected hand. Results: Within 6 weeks after surgery, only 1 patient in conventional rehabilitation group suffered from venous crisis, and the flap survived after the second surgical exploration and anastomosis of blood vessels; there was no occurrence of tendon rupture in patients of 2 groups. After 6 weeks of surgery, there were no statistically significant differences in pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, or grip force of the affected hand between the two groups of patients (P>0.05); the excellent and good ratio of the finger joint range of motion of the affected hand of patients in early rehabilitation group was 11/12, which was higher than 7/12 in conventional rehabilitation group, but there was no statistically significant difference (P>0.05); the affected hand function score of patients in early rehabilitation group was 90±6, which was significantly higher than 83±8 in conventional rehabilitation group (t=2.41, P<0.05); the function rating of the affected hand of patients in early rehabilitation group was obviously better than that in conventional rehabilitation group (Z=2.04, P<0.05). Conclusions: Early rehabilitation treatment for patients with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand after repair surgery can improve hand function, but it would not increase surgery related complications, which is worthy of clinical promotion and application.

[Effect and mechanism of human adipose-derived stem cell exosomes on diabetic peripheral neuropathy].

Objective: To investigate the changes of artemin protein expression in diabetic peripheral neuropathy (DPN) and to explore the regulatory effect of human adipose-derived stem cell (ADSC) exosomes on the change of artemin protein expression. Methods: This research was a prospective observational clinical research combined with experimental research. Thirteen DPN patients (9 males and 4 females, aged 32 to 68 years) who were admitted to the First Affiliated Hospital of Air Force Medical University (hereinafter referred to as our hospital) from May 2022 to October 2023 and met the inclusion criteria were selected as DPN group, and 5 non-diabetes patients (4 males and 1 female, aged 29 to 61 years) who were admitted to our hospital in the same period of time and met the inclusion criteria were selected as control group. The toe nerve or sural nerve tissue in the abandoned tissue after debridement or amputation of patients in the two groups was collected. The pathological changes of nerve tissue were observed after hematoxylin-eosin staining; the protein expressions of S100ß and artemin in nerve tissue were observed after immunofluorescence staining, and the artemin protein expression was quantified; the protein and mRNA expressions of artemin were detected by Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction, respectively (the sample number in DPN group and control group was 13 and 5, respectively). Twelve male C57BL/6 mice aged 3 to 5 days were collected to isolate Schwann cells, and the cells were divided into conventional culture group cultured routinely, high glucose alone group (cultured with high concentration of glucose solution only), and high glucose+exosome group (cultured with high concentration of glucose solution and extracted human ADSC exosomes). After 24 hours of culture, the cell proliferation activity was detected by cell counting kit 8 (n=6). After 48 hours of culture, the protein expression of artemin was detected by Western blotting (n=3). Results: Compared with those in control group, the neural supporting cells decreased and the inflammatory cells increased in the nerve tissue of patients in DPN group, showing typical manifestations of nerve injury. Immunofluorescence staining showed that compared with those in control group, the nuclei was more, and the protein expression of S100ß was lower in nerve tissue of patients in DPN group. The protein expression of artemin in nerve tissue of patients in DPN group was 71±31, which was significantly lower than 1 729±62 in control group (t=76.92, P<0.05). Western blotting detection showed that the protein expression of artemin in nerve tissue of patients in DPN group was 0.74±0.08, which was significantly lower than 0.97±0.06 in control group (t=5.49, P<0.05). The artemin mRNA expression in nerve tissue of patients in DPN group was significantly lower than that in control group (t=7.65, P<0.05). After 24 hours of culture, compared with that in conventional culture group, the proliferation activities of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased (P<0.05); compared with that in high glucose alone group, the proliferation activity of Schwann cells in high glucose+exosome group was significantly increased (P<0.05). After 48 hours of culture, compared with those in conventional culture group, the protein expressions of artemin of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased (P<0.05); compared with that in high glucose alone group, the protein expression of artemin of Schwann cells in high glucose+exosome group was significantly increased (P<0.05). Conclusions: The protein expression of artemin in nerve tissue of DPN patients is lower than that in normal nerve tissue, which may be related to the reduction of proliferation activity of Schwann cells by high glucose. Human ADSC exosomes may improve the proliferation activity of Schwann cells by increasing artemin protein expression, thereby delaying the progression of DPN.

[Influences and mechanism of extracellular vesicles from dermal papilla cells of mice on human hypertrophic scar fibroblasts].

Objective: To investigate the influences and mechanism of extracellular vesicles from dermal papilla cells (DPC-EVs) of mice on human hypertrophic scar fibroblasts (HSFs). Methods: The study was an experimental research. The primary dermal papilla cells (DPCs) of whiskers were extracted from 10 6-week-old male C57BL/6J mice and identified successfully. The DPC-EVs were extracted from the 3rd to 5th passage DPCs by ultracentrifugation, and the morphology was observed through transmission electron microscope and the particle diameter was detected by nanoparticle tracking analyzer (n=3) at 24 h after culture. The 3rd passage of HSFs were divided into DPC-EV group and phosphate buffer solution (PBS) group, which were cultured with DPC-EVs and PBS, respectively. The cell scratch test was performed and cell migration rate at 24 h after scratching was calculated (n=5). The cell proliferation levels at 0 (after 12 h of starvation treatment and before adding DPC-EVs or PBS), 24, 48, 72, and 96 h after culture were detected by using cell counting kit 8 (n=4). The protein expressions of α-smooth muscle actin (α-SMA) and collagen typeⅠ (ColⅠ) in cells at 24 h after culture were detected by immunofluorescence method and Western blotting, and the protein expression of Krüppel-like factor 4 (KLF4) in cells at 24 h after culture was detected by Western blotting. After the 3rd passage of HSFs were cultured with DPC-EVs for 24 h, the cells were divided into blank control group, KLF4 knockdown group, and KLF4 overexpression group according to the random number table. The cells in blank control group were only routinely cultured for 48 h. The cells in KLF4 knockdown group and KLF4 overexpression group were incubated with KLF4 knockdown virus for 24 h, then the cells in KLF4 knockdown group were routinely cultured for 24 h while the cells in KLF4 overexpression group were incubated with KLF4 overexpression virus for 24 h. The protein expressions of KLF4, α-SMA, and ColⅠ in cells were detected by Western blotting at 48 h after culture. Results: At 24 h after culture, the extracted DPC-EVs showed vesicular structure with an average particle diameter of 108.8 nm. At 24 h after scratching, the migration rate of HSFs in PBS group was (54±10)%, which was significantly higher than (29±8)% in DPC-EV group (t=4.37, P<0.05). At 48, 72, and 96 h after culture, the proliferation levels of HSFs in DPC-EV group were significantly lower than those in PBS group (with t values of 4.06, 5.76, and 6.41, respectively, P<0.05). At 24 h after culture, the protein expressions of α-SMA and ColⅠ of HSFs in DPC-EV group were significantly lower than those in PBS group, while the protein expression of KLF4 was significantly higher than that in PBS group. At 48 h after culture, compared with those in blank control group, the protein expression of KLF4 of HSFs in KLF4 knockdown group was down-regulated, while the protein expressions of α-SMA and ColⅠ were both up-regulated; compared with those in KLF4 knockdown group, the protein expression of KLF4 of HSFs in KLF4 overexpression group was up-regulated, while the protein expressions of ColⅠ and α-SMA were down-regulated. Conclusions: The DPC-EVs of mice can inhibit the proliferation and migration of human HSFs and significantly inhibit the expressions of fibrosis markers α-SMA and ColⅠ in human HSFs by activating KLF4.

Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

[Pay attention to the prevention and treatment of deep sternal wound infection after sternotomy].

Deep sternal wound infection (DSWI) is one of the potential and catastrophic complications after cardiac surgery. Despite the use of smaller incisions, routine application of prophylactic antibiotic and optimized blood glucose management, the incidence rate of DSWI still fluctuates between 1% and 5%. The early symptoms and signs of DSWI are not often obvious, making it too late for the clinicians to intervene in the process. Once left untreated, DSWI carries a very high mortality rate. Therefore, early prevention, diagnosis, and appropriate management of DSWI are crucial in preventing its progression to life-threatening outcomes. Considering the clinical severity and treatment complexity of DSWI, this article focuses on preventive experiences in each stage of DSWI, and reconstructive strategies after DSWI happens, raising attention among the medical community regarding DSWI.

[Perioperative management of wounds associated with secondary sternal osteomyelitis and/or mediastinitis after sternotomy and its clinical effects].

Objective: To investigate the perioperative management of wounds associated with secondary sternal osteomyelitis and/or mediastinitis after sternotomy, and to evaluate its clinical effects. Methods: This study was a retrospective observational study. From January 2017 to December 2022, 36 patients with wounds associated with secondary sternal osteomyelitis and/or mediastinitis after sternotomy who were conformed to the inclusion criteria were admitted to the Burn Center of PLA of the First Affiliated Hospital of Air Force Medical University, including 23 males and 13 females, aged 25 to 81 years. Preparation for surgery was made. For patients with suspected retrosternal mediastinal abscess cavity, all cancellous bone of the unhealed sternum was bitten off to fully expose the retrosternal mediastinum, remove the source of infection and granulation tissue, and to fill the sternum defect with flipped unilateral pectoralis major muscle. For patients who had no retrosternal mediastinal infection but had fresh granulation tissue in unhealed sternal wounds, the necrotic tissue and a small amount of necrotic sternum were palliatively removed, and bilateral pectoralis major muscles were advanced and abutted to cover the sternal defect. After the skin in the donor area was closed by tension-relieving suture, continuous vacuum sealing drainage was performed, and continuous even infusion and lavage were added 24 hours later. The thorax was fixed with an armor-like chest strap, the patients were guided to breathe abdominally, with both upper limbs fixed to the lateral chest wall using a surgical restraint strap. The bacterial culture results of wound exudation specimens on admission were recorded. The wound condition observed during operation, debridement method, muscle flap covering method, intraoperative bleeding volume, days of postoperative infusion and lavage, lavage solution volume and changes on each day, and postoperative complications and wound healing time were recorded. After discharge, the wound healing quality, thorax shape, and mobility functions of thorax and both upper limbs were evaluated during follow-up. The stability and closure of sternum were observed by computed tomography (CT) reexamination. Results: On admission, among 36 patients, 33 cases were positive and 3 cases were negative in bacterial culture results of wound exudation specimens. Intraoperative observation showed that 26 patients had no retrosternal mediastinal infection but had fresh granulation tissue in unhealed sternal wounds, palliative debridement was performed and bilateral pectoralis major muscles were advanced and abutted to cover the defect. In 10 patients with suspected retrosternal mediastinal abscess cavity, the local sternum was completely removed by bite and the defect was covered using flipped unilateral pectoralis major muscle. During the operation, one patient experienced an innominate vein rupture and bleeding of approximately 3 000 mL during mediastinal exploration, and the remaining patients experienced bleeding of 100-1 000 mL. Postoperative infusion and lavage were performed for 4-7 days, with a lavage solution volume of 3 500-4 500 mL/d. The lavage solution gradually changed from dark red to light red and finally clear. Except for 1 patient who had suture rupture caused by lifting the patient under the armpit during nursing on the 3rd day after surgery, the wounds of the other patients healed smoothly after surgery, and the wound healing time of all patients was 7-21 days. Follow-up for 3 to 9 months after discharge showed that the patient who had suture rupture caused by armpit lifting died due to multiple organ failure. In 1 patient, the armor-like chest strap was removed 2 weeks after surgery, and the shoulder joint movement was not restricted, resulting in local rupture of the suture, which healed after dressing change. The wounds of the remaining patients healed well, and they resumed their daily life. The local skin of patient's pectoralis major muscle defect was slightly sunken and lower than that of the contralateral thorax in the patients undergoing treatment of pectoralis major muscle inversion, while no obvious thoracic deformity was observed in patients undergoing treatment with pectoralis major muscle propulsion and abutment. The chest and upper limb movement in all patients were slightly limited or normal. CT reexamination results of 10 patients showed that the sternum was stable, the local sternum was closed or covered completely with no lacuna or defects. Conclusions: Once the wound associated with secondary sternal osteomyelitis and/or mediastinitis after sternotomy is formed, individualized and precise debridement should be performed as soon as possible, different transfer ways of pectoralis major muscle flap should be chosen to cover the defect, and postoperative continuous infusion and lavage together with strict thorax and shoulder joint restraint and immobilization should be performed. This treatment strategy can ensure good wound healing without affecting the shape and function of the donor area.

[Bilateral visual pathway invasion of occipital astrocytoma: a case report].

A 33-year-old female presented to the ophthalmology clinic with right periorbital redness and pain for 12 hours. CT revealed right optic nerve thickening and enlargement. Cranial MRI demonstrated abnormalities in the corpus callosum, bilateral hippocampi, thalamus, basal ganglia, temporal-parietal lobes, and the left frontal lobe. Ocular B-scan ultrasound showed elevated optic disc and high echogenic signals in the right vitreous cavity. The patient had a history of surgical resection, radiation therapy, and chemotherapy for a left occipital glioma two years prior, with pathology indicating astrocytoma (World Health Organization Grade Ⅱ). Combining the patient's history and diagnostic findings, the confirmed diagnosis is bilateral occipital astrocytoma with invasion into the right transverse sinus, bilateral optic pathways involvement related to the left occipital astrocytoma, and seeding of astrocytoma in the right vitreous cavity.

[Role of SPP1 in acute kidney injury induced by renal ischemia-reperfusion in rats].

OBJECTIVE: To investigate the role of SPP1 gene in acute kidney injury induced by renal ischemia-reperfusion injury (IRI). METHODS: Twelve Sprague-Dawley rats were randomly divided into sham group and IRI group (n=6) and subjected to sham operation and renal ischemia for 30 min induced by penal pedicle clamping using non-traumatic microvascular clamps, respectively.Serum creatinine and blood urea nitrogen levels were detected, and PAS staining was used for pathological examination of the kidneys in the two groups.The renal expressions of SPP1, α-SMA and caspase-3 were detected using immunohistochemistry and immunofluorescent staining.In cultured renal tubular epithelial cells (HK-2 cells), Western blotting was performed to detect the changes in expressions of SPP1, caspase-3, and Kim-1 proteins following hypoxiareoxygenation (H/R) and transfection with si-NC or si-SPP1;flow cytometry was employed to analyze apoptosis of the treated cells. RESULTS: Renal IRI caused significant elevations of serum creatinine and blood urea nitrogen levels (P<0.05) and induced severe shedding and necrosis of the renal tubular epithelial cells in the rats, resulting also in significantly up-regulated renal expressions of SPP1, α-SMA and caspase-3(P<0.05).In HK-2 cells, H/R significantly increased the protein expression levels of SPP1, caspase-3, and Kim-1(P<0.05), and compared si-NC transfection, transfection with SPP1 obviously reduced caspase-3 and Kim-1 expressions and lowered apoptosis rate of the cells with H/R exposure (P<0.05). CONCLUSION: SPP1 is up-regulated in the kidneys of rats with renal IRI, and down-regulation of SPP1 expression can inhibit H/R-induced apoptosis of renal tubular epithelial cells.

[Clinical effects of autologous split-thickness skin grafting for prefabricating urethra combined with scrotal flap in repairing middle urethral defect with penile defect].

Objective: To investigate the clinical effects of autologous split-thickness skin grafting for prefabricating urethra combined with scrotal flap in repairing middle urethral defect with penile defect. Methods: The retrospective observational study was conducted. Eight male patients (aged 14 to 58 years) with middle urethral defect and penile defect caused by various injuries who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University from January 2015 to January 2022. The length of urethral defect was 3 to 5 cm, and the wound area of penile defect after debridement was 5.0 cm×2.5 cm to 7.0 cm×5.5 cm. All the patients underwent autologous split-thickness skin grafting for prefabricating defect urethra in stage Ⅰ, and urethral anastomosis was performed and unilateral scrotal flap was transferred to reconstruct urethra and penis in stage Ⅱ. The area of scrotal flap was 6.0 cm×3.0 cm to 8.0 cm×6.0 cm. The wound in the donor area of skin graft was covered by oil gauze, and the wound of flap donor area was sutured directly. On the 7th day after the operation of stage Ⅱ, the survival of the flap was observed. In 3 weeks after the operation of stage Ⅱ, the urinary flow rate was measured by the urinary flow rate detector (urinary flow rate >15 mL/s was regarded as unobstructed urination), the urinary fistula and erectile function were observed, and the self-made therapeutic satisfaction questionnaire was used to investigate the therapeutic satisfaction degree of patients. During follow-up, the appearance of the flap recipient area was observed, the Vancouver scar scale (VSS) was used to evaluate the scar situation in the donor areas of skin graft and flap, the urinary flow rate was detected as before, the urethral stricture, urinary fistula, and erectile function were observed, and the therapeutic satisfaction degree of patients was investigated. Results: On the 7th day after the operation of stage Ⅱ, the flaps survived completely in 8 patients. In 3 weeks after the operation of stage Ⅱ, the urinary flow rate was 25.3 (18.0, 38.5) mL/s, with unobstructed urination, without urinary fistula and with erectile function, and the score of therapeutic satisfaction degree was 14.3 (14.0, 15.0). During follow-up of 1 to 7 years, the flap recipient area of 8 patients was full in appearance and not swollen, with similar color to the surrounding tissue; the VSS scores of the donor areas of skin graft and flap were 11.5 (10.0, 13.0) and 10.5 (9.3, 12.0), respectively, the urinary flow rate was 24.6 (17.7, 34.1) mL/s, with no urethral stricture, urinary fistula, and erectile dysfunction, and the score of therapeutic satisfaction degree was 13.5 (13.3, 14.8). Conclusions: Autologous split-thickness skin grafting for prefabricating urethra combined with scrotal flap in repairing the urethral and penile defects not only reconstructs the structure of urethra and the shape of penis, but also restores the sensation and erectile function of penis, with few postoperative complications, no obvious scar hyperplasia, and high satisfaction degree of patients, which is worthy of clinical promotion.

[Clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation].

Objective: To explore the clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation. Methods: A retrospective observational study was conducted. From January to August 2021, 5 patients with secondary rejection wounds after brain pacemaker implantation who met the inclusion criteria were admitted to the Wound Repair Center of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, including 3 males and 2 females, aged 56-69 years, with the wound developed at the pulse generator implantation site in the chest in 2 cases, at the connection site of the wire and electrode behind the ear in 2 cases, and at both the chest and the back of the ear in 1 case. All the wounds were repaired by pedicled omental flap transplantation. The wound area after debridement was 2-15 cm2. After operation, the wound healing and related complications (pain, infection, incisional hernia, omental flap necrosis, etc.) were observed. During follow-up, the recurrence of the wound was observed. Results: The wounds of all 5 patients healed within 2 weeks after operation, without related complications. During follow up of 12-18 months, 1 patient got a recurrence of rejection wound behind the left ear 4 months after surgery and eventually had the brain pacemaker removed; the other 4 patients had no recurrence of wounds. Conclusions: Pedicled omental flap transplantation can repair the secondary rejection wounds after brain pacemaker implantation safely and effectively, with few postoperative complications.

[Association of category of dietary intake and physical activity with the risk of mortality in patients with type 2 diabetes mellitus: a prospective cohort study].

Objective: To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM). Methods: Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM. Results: As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio (HR)=0.81, 95%CI: 0.70-0.94] and a 33% lower risk of all-cause mortality (HR=0.67, 95%CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% (HR=0.50, 95%CI: 0.45-0.56), 50% (HR=0.50, 95%CI: 0.41-0.61), and 27% (HR=0.73, 95%CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% (HR=0.45, 95%CI: 0.38-0.53), 56% (HR=0.44, 95%CI: 0.32-0.59), and 40% (HR=0.60, 95%CI: 0.44-0.82), respectively. Conclusion: Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

[Systematic errors and control measures during epidemiological surveys of myopia among schoolchildren and adolescents].

Systematic errors and bias are common problems that affect the validity and reliability of epidemiological surveys of myopia among schoolchildren and adolescents worldwide. To provide guidance for standardization of such surveys, the perniciousness, causes and control measures of errors in surveying respondents and bias during the examination and diagnosis are discussed in this article. It is emphasized that controlling systematic errors and bias is the key to ensuring the quality of an epidemiological survey of pediatric and adolescent myopia.

Effects of direct-fed microbial supplementation on performance and immune parameters of lactating dairy cows.

We evaluated the effects of supplementing bacterial direct-fed microbial (DFM) on performance, apparent total-tract digestibility, rumen fermentation, and immune parameters of lactating dairy cows. One hundred fourteen multiparous Holstein cows (41 ± 7 DIM) were used in a randomized complete block design with an experiment comprising 14 d of a covariate (pre-experimental sample and data collection) and 91 d of an experimental period. Cows were blocked based on energy-corrected milk (ECM) yield during the covariate period and the following treatments were randomly assigned within each block: (1) control (CON), corn silage-based total mixed ration without DFM; (2) PRO-A, basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 109 cfu/d; and 3) PRO-B, basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and Bacillus licheniformis at 11.8 × 109 cfu/d. Milk yield, dry matter intake (DMI), and body weight were measured daily, while milk samples for component analysis were taken on 2 consecutive days of each week of data collection. Feces, urine, rumen, and blood samples were taken during the covariate period, wk 4, 7, 10, and 13 for estimation of digestibility, N-partitioning, rumen fermentation, plasma nutrient status and immune parameters. Treatments had no effect on DMI and milk yield. Fat-corrected milk (3.5% FCM) and milk fat yield were improved with PRO-B, while milk fat percent and feed efficiency (ECM/DMI) tended to increase with PRO-B compared with PRO-A and CON. Crude fat digestibility was greater with PRO-B compared with CON. Feeding CON and PRO-A resulted in higher total volatile fatty acid concentration relative to PRO-B. Percentage of neutrophils tended to be reduced with PRO-A compared with CON and PRO-B. The mean fluorescence intensity (MFI) of anti-CD44 antibody on granulocytes tended to be higher in PRO-B compared with CON. The MFI of anti-CD62L antibody on CD8+ T cells was lower in PRO-A than PRO-B, with PRO-A also showing a tendency to be lower than CON. This study indicates the potential of DFM to improve fat digestibility with consequential improvement in fat corrected milk yield, feed efficiency and milk fat yield by lactating dairy cows. The study findings also indicate that dietary supplementation with DFM may augment immune parameters or activation of immune cells, including granulocytes and T cells; however, the overall effects on immune parameters are inconclusive.