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.

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.

[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.

[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.

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.

[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.

HOCl Rapidly Kills Corona, Flu, and Herpes to Prevent Aerosol Spread.

The COVID-19 pandemic has escalated the risk of SARS-CoV-2 transmission in the dental practice, especially as droplet-aerosol particles are generated by high-speed instruments. This has heightened awareness of other orally transmitted viruses, including influenza and herpes simplex virus 1 (HSV1), which are capable of threatening life and impairing health. While current disinfection procedures commonly use surface wipe-downs to reduce viral transmission, they are not fully effective. Consequently, this provides the opportunity for a spectrum of emitted viruses to reside airborne for hours and upon surfaces for days. The objective of this study was to develop an experimental platform to identify a safe and effective virucide with the ability to rapidly destroy oral viruses transported within droplets and aerosols. Our test method employed mixing viruses and virucides in a fine-mist bottle atomizer to mimic the generation of oral droplet-aerosols. The results revealed that human betacoronavirus OC43 (related to SARS-CoV-2), human influenza virus (H1N1), and HSV1 from atomizer-produced droplet-aerosols were each fully destroyed by only 100 ppm of hypochlorous acid (HOCl) within 30 s, which was the shortest time point of exposure to the virucide. Importantly, 100 ppm HOCl introduced into the oral cavity is known to be safe for humans. In conclusion, this frontline approach establishes the potential of using 100 ppm HOCl in waterlines to continuously irrigate the oral cavity during dental procedures to expeditiously destroy harmful viruses transmitted within aerosols and droplets to protect practitioners, staff, and other patients.

Asthenopia prevalence and vision impairment severity among students attending online classes in low-income areas of western China during the COVID-19 pandemic.

INTRODUCTION: This study explored the impact of online learning during the coronavirus disease 2019 (COVID-19) pandemic on asthenopia and vision impairment in students, with the aim of establishing a theoretical basis for preventive approaches to vision health. METHODS: This balanced panel study enrolled students from western rural China. Participant information was collected before and during the COVID-19 pandemic via questionnaires administered at local vision care centres, along with clinical assessments of visual acuity. Paired t tests and fixed-effects models were used to analyse pandemic-related differences in visual status. RESULTS: In total, 128 students were included (mean age before pandemic, 11.82 ± 1.46 years). The mean total screen time was 3.22 ± 2.90 hours per day during the pandemic, whereas it was 1.97 ± 1.90 hours per day in the pre-pandemic period (P<0.001). Asthenopia prevalence was 55% (71/128) during the pandemic, and the mean visual acuity was 0.81 ± 0.30 logarithm of the minimum angle of resolution; these findings indicated increasing vision impairment, compared with the pre-pandemic period (both P<0.001). Notably, asthenopia prevalence increased by two- to three-fold, compared with the pre-pandemic period. An increase in screen time while learning was associated with an increase in asthenopia prevalence (P=0.034). CONCLUSION: During the COVID-19 pandemic, students spent more time on online classes, leading to worse visual acuity and vision health. Students in this study reported a significant increase in screen time, which was associated with increasing asthenopia prevalence and worse vision impairment. Further research is needed regarding the link between online classes and vision problems.

[Treatment response of a two-dose regimen of dose-adjusted inotuzumab ozogamicin in relapsed/refractory B-cell acute lymphoblastic leukemia].

Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.

[Effects of Krüppel-like factor 4 on inflammatory response and organ injury in septic mice].

Objective: To explore the expression characteristics and role of Krüppel-like factor 4 (KLF4) in macrophage inflammatory response and its effects on inflammatory response and organ injury in septic mice, so as to lay a theoretical foundation for targeted treatment of burns and trauma sepsis. Methods: The method of experimental research was used. Mouse RAW264.7 macrophages and primary peritoneal macrophages (PMs) isolated from 10 male C57BL/6J mice aged 6-8 weeks were used for the experiments. RAW264.7 macrophages and PMs were treated with endotoxin/lipopolysaccharide (LPS) for 0 (without treatment), 1, 2, 4, 6, 8, 12, and 24 h, respectively, to establish macrophage inflammatory response model. The mRNA expression of interleukin 1ß (IL-1ß), IL-6, CC chemokine ligand 2 (CCL2) and tumor necrosis factor-α (TNF-α) were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR), and the LPS treatment time was determined for some of the subsequent experiments. RAW264.7 macrophages were treated with LPS for 0 and 8 h, the localization and protein expression of KLF4 were detected by immunofluorescence method, transcriptome sequencing of the cells was performed using the high-throughput sequencing technology platform, and the differently expressed genes (DEGs) between the two time points treated cells were screened by DESeq2 software. RAW264.7 macrophages and PMs were treated with LPS for 0, 1, 2, 4, 6, 8, 12, and 24 h, respectively, and the mRNA and protein expressions of KLF4 were detected by real-time fluorescence quantitative RT-PCR and Western blotting, respectively. RAW264.7 macrophages were divided into negative control (NC) group and KLF4-overexpression group according to the random number table, which were treated with LPS for 0 and 8 h respectively after transfection of corresponding plasmid. The mRNA expressions of KLF4, IL-1ß, IL-6, CCL2, and TNF-α were detected by real-time fluorescence quantitative RT-PCR, while the protein expression of KLF4 was detected by Western blotting. The number of samples in aforementioned experiments was all 3. Forty male C57BL/6J mice aged 6-8 weeks were divided into KLF4-overexpression group and NC group (with 20 mice in each group) according to the random number table, and the sepsis model of cecal ligation perforation was established after the corresponding transfection injection was injected respectively. Twelve mice were selected from each of the two groups according to the random number table, and the survival status within 72 hours after modeling was observed. Eight hours after modeling, the remaining 8 mice in each of the two groups were selected, the eyeball blood samples were collected to detect the levels of IL-1ß and IL-6 in serum by enzyme-linked immunosorbent assay, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum by dry chemical method. Subsequently, the heart, lung, and liver tissue was collected, and the injury was observed after hematoxylin-eosin staining. Data were statistically analyzed with independent sample t test, Cochran & Cox approximate t test, one-way analysis of variance, Dunnett test, Brown-Forsythe and Welch one-way analysis of variance, Dunnett T3 test, log-rank (Mantel-Cox) test. Results: Compared with that of LPS treatment for 0 h, the mRNA expressions of IL-1ß in RAW264.7 macrophages treated with LPS for 6 h and 8 h, the mRNA expressions of IL-6 in RAW264.7 macrophages treated with LPS for 4-12 h, the mRNA expressions of CCL2 in RAW264.7 macrophages treated with LPS for 8 h and 12 h, and the mRNA expressions of TNF-α in RAW264.7 macrophages treated with LPS for 4-8 h were significantly up-regulated (P<0.05 or P<0.01), while the mRNA expressions of IL-1ß and CCL2 in PMs treated with LPS for 4-8 h, the mRNA expressions of IL-6 in PMs treated with LPS for 2-24 h, and the mRNA expressions of TNF-α in PMs treated with LPS for 2-12 h were significantly up-regulated (P<0.05 or P<0.01). Eight hours was selected as the LPS treatment time for some of the subsequent experiments. KLF4 mainly located in the nucleus of RAW264.7 macrophages. Compared with those of LPS treatment for 0 h, the protein expression of KLF4 in RAW264.7 macrophages treated with LPS for 8 h was obviously decreased, and there were 1 470 statistically differentially expressed DEGs in RAW264.7 macrophages treated with LPS for 8 h, including KLF4 with significantly down-regulated transcriptional expression (false discovery rate<0.05, log2 (fold change)=-2.47). Compared with those of LPS treatment for 0 h, the mRNA expressions of KLF4 in RAW264.7 macrophages treated with LPS for 6-24 h, the protein expressions of KLF4 in RAW264.7 macrophages and PMs treated with LPS for 1-24 h, and the mRNA expressions of KLF4 in PM treated with LPS for 4-24 h were significantly decreased (P<0.05 or P<0.01). Compared with those in NC group, the mRNA (with t' values of 17.03 and 8.61, respectively, P<0.05 or P<0.01) and protein expressions of KLF4 in RAW264.7 macrophages treated with LPS for 0 h and 8 h in KLF4-overexpression group were significantly increased, the mRNA expressions of IL-6 and CCL2 increased significantly in RAW264.7 macrophages treated with LPS for 0 h (with t values of 6.29 and 3.40, respectively, P<0.05 or P<0.01), while the mRNA expressions of IL-1ß, IL-6, CCL2, and TNF-α decreased significantly in RAW264.7 macrophages treated with LPS for 8 h (with t values of 10.52, 9.60, 4.58, and 8.58, respectively, P<0.01). The survival proportion of mice within 72 h after modeling in KLF4-overexpression group was significantly higher than that in NC group (χ2=4.01, P<0.05). Eight hours after modeling, the serum levels of IL-1ß, IL-6 and ALT, AST of mice in KLF4-overexpression group were (161±63), (476±161) pg/mL and (144±24), (264±93) U/L, respectively, which were significantly lower than (257±58), (654±129) pg/mL and (196±27), (407±84) U/L (with t values of 3.16, 2.44 and 4.04, 3.24, respectively, P<0.05 or P<0.01) in NC group. Eight hours after modeling, compared with those in NC group, the disorder of tissue structure of heart, lung, and liver, inflammatory exudation, and pathological changes of organ parenchyma cells in KLF4-overexpression group were obviously alleviated. Conclusions: The expression of KLF4 is significantly down-regulated in LPS-induced macrophage inflammatory response, which significantly inhibits the macrophage inflammatory response. KLF4 significantly enhances the survival rate of septic mice and alleviates inflammatory response and sepsis-related organ injury.