BACKGROUND:High tibial osteotomy results in massive blood loss during the perioperative period.Tranexamic acid can effectively reduce perioperative blood loss.However,the method of tranexamic acid application has not been unified. OBJECTIVE:To investigate the effect and safety of different methods of tranexamic acid on perioperative blood loss in the high tibial osteotomy. METHODS:A total of 160 patients who underwent primary unilateral high tibial osteotomy in the Binzhou Medical University Hospital from January 2019 to December 2021,including 69 males and 91 females,were randomly divided into four groups(n=40 per group).Among them,40 patients were given an intravenous infusion of saline containing 2 g tranexamic acid 10 minutes before tourniquet release(venous group);40 patients were given an intravenous infusion of 1 g tranexamic acid and 1 g tranexamic acid was injected through a drainage tube after the closure of the incision(combined group);40 patients were given 2 g tranexamic acid infusion into drainage tube after the closure of the incision(perfusion group);an additional 40 patients were given an intravenous infusion of the same amount of normal saline(blank group).The general information was compared among the four groups of patients.The hemoglobin,hematocrit,intraoperative blood loss,drainage volume,blood transfusion rate,incision complication,and the incidence of deep vein thrombosis were recorded on days 1,3 and 5 after operation in the four groups.The total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in general information among the four groups.(2)No significant difference was found in intraoperative blood loss among the four groups.(3)The maximum decreased values of hemoglobin and hematocrit on days 1,3 and 5 after operation,drainage volume,total blood loss and hidden blood loss were all ranked as the combined group

Objective To investigate the correlation between baseline data,early treatment response and prognosis in children with acute lymphoblastic leukemia(ALL).Methods Ninety-two children with ALL were divided into the endpoint event group(19 cases)and the event-free survival group(73 cases)according to whether there was an endpoint event(recurrence or death).The age and gender at initial diagnosis were recorded.Initial white blood cell count(WBC),platelet count(PLT),immunophenotype,chromosome karyotype,fusion gene,prednisone test,bone marrow remission status on the 15th day of induction chemotherapy and minimal residual disease(MRD)on the 15th,33rd and 55th day of induction chemotherapy were detected.The correlation between the above baseline data and early treatment response and the occurrence of endpoint event in children with ALL was analyzed.Logistic regression was used to analyze influencing factors of endpoint events in children with ALL.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of baseline data and early treatment response to endpoint events in children with ALL.Results The proportion of WBC≥100×109/L at first diagnosis,prednisone poor reaction and positive MRD on the 33rd day of induction chemotherapy were higher in the endpoint event group than those in the event-free survival group(P<0.05),and there were no significance differences in remaining indicators(P>0.05).Logistic regression analysis showed that prednisone poor reaction and positive MRD on the 33rd day of induction chemotherapy were risk factors for endpoint event in children with ALL(P<0.05),and the combined value of the two indicators was better than that of a single indicator in predicting endpoint events in children with ALL.Conclusion Prednisone poor reaction and positive MRD on the 33rd day of induction chemotherapy are associated with recurrence and death in children with ALL.

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

In November 4, 2016, a 1 year and 3 months old male patient with face and neck scald complicated with severe scald of oropharynx was admitted to Guangzhou Red Cross Hospital 1 hour after injury. The child developed upper respiratory tract obstruction 2 hours after injury, therefore tracheotomy and intubation were performed immediately to establish an artificial airway, and symptomatic treatments such as anti-infection, fluid replacement, and dressing change were conducted. On the 10th day after injury, the child had difficult breathing during the test tube blocking before extubation, and it was difficult to extubate. Symptomatic treatments such as ventilator assisted ventilation and strengthened anti-infection were continued. On the 17th day after injury, extubation plan was adjusted. Thirty minutes before extubation, phenobarbital was injected intramuscularly for sedation, and atropine was used to reduce airway secretions, after which extubation was successful. After 21 days of treatment, the child was cured and discharged. In the treatment of this case, high attention was paid to the important influence of children′s mental factors among causes of difficult extubation, which provided a reference for clinical treatment of extubation in children with tracheal tube after tracheotomy.

Objective: To analyze the causes of complication of early acute kidney injury (AKI) in four severely burned patients, and to explore the related treatment methods. Methods: The clinical data of 4 patients with severe burn complicated with early AKI admitted to Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan University (hereinafter referred to as our hospital) from June 2014 to December 2017 were retrospectively analyzed. All the patients were male, aged 23-33 (30±5) years old, with depth of burns ranged from deep partial-thickness to full-thickness, complicated with myofascial compartment syndrome of extremities and varying degrees of striated muscle injury, and treated in other hospitals before transfer to our hospital. The patients were numbered from small to large according to the total burn area. The total burn area of patients No. 1, 2, 3, and 4 was 10%, 80%, 90%, and 95% total body surface area respectively, their occurrence time of early AKI was 48, 11, 29, and 48 hours after injury respectively, and their time of arriving our hospital was 60, 11, 29, and 144 hours after injury respectively. Hypovolemic shock occurred in patients No. 2 and 3 at admission to our hospital. All the patients received continuous renal replacement therapy (CRRT) after admission to our hospital. Under the support of hemodynamic monitoring and organ function monitoring, the limbs complicated with myofascial compartment syndrome were incised, thorough decompression exploration was performed, and necrotic muscle tissue was removed or amputation was performed. After escharectomy and decompression of limbs, fresh granulation wounds were formed by temporarily covering wounds with Jieya dressing skin or pig skin, multiple debridements, and vacuum sealing drainage. Fresh granulation wounds and other wounds underwent staged eschar excision and shaving were covered with autologous Meek skin graft, particulate skin graft, reticular skin graft and small skin graft respectively. The treatment outcome, CRRT time, operation times, time of recovery of serum creatinine and myoglobin, length of hospital stay, and follow-up were recorded. Results: All the 4 patients were cured after transfer to our hospital. Among them, totally 5 limbs of patients No. 1 and No. 4 underwent amputation because of complication of myofascial compartment syndrome and a large amount of necrotic muscle which could not be preserved. Patients No. 1, 2, 3, and 4 were treated with CRRT for 19, 35, 14, and 25 days respectively and performed with operation for 5, 6, 10, 8 times respectively. Serum creatinine of patients No. 1, 2, 3, and 4 returned to normal on 22, 35, 37, and 48 days after transfer respectively, and their serum myoglobin returned to normal on 18, 28, 25, and 30 days after transfer respectively. Patients No. 1, 2, 3, and 4 were hospitalized for 52, 105, 148, and 156 days and discharged after basic wound healing. Follow-up for 1 to 36 months showed no abnormal renal function in 4 patients. Conclusions The early AKI in patients No. 1 and 4 was caused by rhabdomyolysis after severe burn complicated with myofascial compartment syndrome, while that of the other 2 cases were also related to hypovolemic shock and poor renal perfusion. The success rate of early AKI treatment in severely burned patients can be effectively improved by removing the causes of diseases at the same time of CRRT and actively treating burn wounds under the support of organ function and hemodynamic monitoring.

Objective: To investigate the effect and regulatory mechanism of Smurf2 on the negative regulator Smad7 of TGF-β1/Smad signaling pathway in hypertrophic scar fibroblasts. Methods: From January to October 2014, 8 patients with hypertrophic scar after burn were admitted. The age of patients ranged from 1 year 8 months to 7 years, and the time of scar hyperplasia ranged from 2 to 12 months. The residual normal skin of the same patient was used as the control. The fibroblasts were isolated from hypertrophic scar and normal skin respectively and cultured. The third to fifth passage cells were used for the experiments. ① The protein expression of Smad7 in the two groups was detected by Western Blot. ② Hypertrophic scar fibroblasts and normal skin fibroblasts were treated with exogenous TGF-β1 at concentration of 10 ng/ml for 0 min, 5 min, 15 min, 30 min, 1 h, 2 h and 12 h. The expression of Smad7 protein and mRNA were detected by Western Blot and RT-PCR, respectively. ③ The cell lysates of the two groups were collected and incubated with the ubiquitin mixture for 1 h, 2 h and 6 h at 37℃, respectively. The degradation level of Smad7 protein was detected by Western Blot. ④ The cell lysate of hypertrophic scar fibroblasts was collected and incubated with ubiquitin mixture with or without proteasome inhibitor (MG132: MG115=1: 1) to study its inhibitory effect on the degradation of Smad7 in vitro. ⑤ Immunoprecipitation (IP) technique was used to detect the interaction between Smad 7 and E3 ubiquitin ligase Smurf2 in hypertrophic scar fibroblasts. ⑥ The expression of Smad7 protein in hypertrophic scar fibroblasts stimulated by TGF-β1 after Smurf2 silencing by small interference RNA (siRNA) technique were detected by Western blot. Results: ① There was no significant difference in the expression level of Smad7 protein between hypertrophic scar and normal skin fibroblasts(t=0.76, P=0.46). ② Expressions of Smad7 mRNA and protein in normal skin fibroblasts stimulated by exogenous TGF-β1 gradually increased in a time-dependent manner(P<0.05). The expression of Smad7 mRNA in the hypertrophic scar fibroblasts increased at all-time points except at 5min , (P<0.05), while there was no significant difference in the expression level of Smad7 protein at all-time points with or without TGF-β1 stimulation(P>0.05). ③ Degradation of Smad7 protein was enhanced in hypertrophic scar fibroblasts (the expression level of Smad 7 protein at each time point was compared with that of the control group and the last time point, P<0.05), while there was no significant difference in Smad7 protein degradation in normal skin fibroblasts(P=0.162). ④ Enhanced degradation of Smad7 in hypertrophic scar fibroblasts was blocked by the addition of the proteasome inhibitors MG132/MG115. ⑤ In hypertrophic scar fibroblasts, the Smurf2-Smad7 complex was detected, which indicated the interaction between Smurf2 and Smad7 in hypertrophic scar fibroblasts. ⑥ The expression of Smad7 protein was not increased in the hypertrophic scar fibroblasts stimulated by TGF-β1, whereas the stimulation of TGF-β1 increased the expression of Smad7 protein after silencing of Smurf2 gene expression. Conclusions In the hypertrophic scar fibroblasts, Smurf 2 attenuates the inhibitory effect of Smad 7 on TGF-β1 signaling pathway through the degradation of Smad7 by ubiquitination, which may be involved in the formation of hypertrophic scar.

Objective To study and analyze of entecavir dispersible tablets on the treatment of patients with decompensated hepatitis B cirrhosis. Methods From February 2014 to September 2016, 100 patients with decompensated hepatitis B cirrhosis were randomly divided into the control group and the experimental group, 50 patients in each group. The control group were received routine treatment, while the experimental group were received entecavir dispersible tablets treatment on the basis of conventional treatment. The therapeutic effects in the two groups were compared and analyzed. Results The effective rate in the experimental group was 92.0%, and 70.0% in the control group. The effective rate in the experimental group was significantly higher than that in the control group, the difference has statistically significant (P<0.05). The Child-pugh score in the experimental group was (6.12±1.43) points, and the score in the control group was (7.23±1.95) points. The score in the control group was significantly higher than that in the experimental group, with statistical difference (P<0.05). The negative rate of HBeAg in the experimental group was 22.0%, while 86% in the control group the difference has statistically significant (P<0.05). Conclusion The clinical effect is better which entecavir dispersible tablets is used in the treatment of the patients with decompensated hepatitis B cirrhosis, which can improve the treatment efficiency to a great extent, recover the liver function, has the further promotion and application significance.

Objective: To explore the effects of silencing Smad ubiquitination regulatory factor 2 (Smurf2) on the secretion of transforming growth factor beta 1 (TGF-β₁), alpha-smooth muscle actin (α-SMA), and collagen type Ⅰ by human hypertrophic scar-derived fibroblasts. Methods: The human normal skin-derived fibroblasts and hypertrophic scar-derived fibroblasts were cultured with explant culture technique from the normal skin and hypertrophic scar tissue, which was obtained from 9 patients with hypertrophic scars after burn. Two kinds of fibroblasts of the third passage were both divided into 6 groups according to the random number table, with 9 wells in each group. Fibroblasts in blank control group were cultured for 72 h without transfection of any small interfering RNA (siRNA), fibroblasts in negative control group were for cultured for 72 h after transfected with non-target siRNA, fibroblasts in Smurf2 siRNA group were cultured for 72 h after transfected with 100 nmol/L Smurf2 siRNA, fibroblasts in blank control+ TGF-β₁ group were cultured for 72 h without transfection of any siRNA and then treated with 10 ng/mL TGF-β₁ for 6 h, fibroblasts in negative control+ TGF-β₁ group were cultured for 72 h after transfected with non-target siRNA and then treated with 10 ng/mL TGF-β₁ for 6 h, fibroblasts in Smurf2 siRNA+ TGF-β₁ group were cultured for 72 h after transfected with Smurf2 siRNA and then treated with 10 ng/mL TGF-β₁ for 6 h. (1) The protein and mRNA expression levels of Smurf2 of the two kinds of cells in blank control group, negative control group, and Smurf2 siRNA group were assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively. (2) The content of TGF-β₁ in the cell culture supernatant of the two kinds of cells in blank control group and Smurf2 siRNA group was determined by enzyme-linked immunosorbent assay (ELISA). (3) The protein expression levels of α-SMA of the two kinds of cells in the 6 groups were assessed by Western blotting. The content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in the 6 groups was determined by ELISA. (4) The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in the 6 groups were assessed by RT-PCR. The sample numbers of each group in the above experiments were all 9. Data were processed with analysis of variance of factorial design and Bonferroni test. Results: (1) The protein and mRNA expression levels of Smurf2 of the two kinds of cells in Smurf2 siRNA group were significantly lower than those in blank control group and negative control group (with P values below 0.05). The protein and mRNA expression levels of Smurf2 of the two kinds of cells in blank control group and negative control group were close (with P values above 0.05). (2) The content of TGF-β₁ in the cell culture supernatant of hypertrophic scar-derived fibroblasts in blank control group and Smurf2 siRNA group was respectively (4.34±0.56) and (2.14±0.28) pg/mL, which was significantly higher than (1.52±0.20) and (1.41±0.18) pg/mL of normal skin-derived fibroblasts respectively (with P values below 0.05). In hypertrophic scar-derived fibroblasts, the content of TGF-β₁ in the cell culture supernatant in Smurf2 siRNA group was significantly lower than that in blank control group (P<0.05). In normal skin-derived fibroblasts, the content of TGF-β₁ in the cell culture supernatant in Smurf2 siRNA group was close to that in blank control group (P>0.05). (3) The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in blank control+ TGF-β₁ group were significantly higher than those in blank control group (with P values below 0.05). The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in negative control+ TGF-β₁ group were significantly higher than those in negative control group (with P values below 0.05). The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in Smurf2 siRNA group were close to those in blank control group and negative control group (with P values above 0.05). The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in Smurf2 siRNA+ TGF-β₁ group were significantly lower than those in blank control+ TGF-β₁ group and negative control+ TGF-β₁ group (with P values below 0.05). (4) The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in blank control+ TGF-β₁ group were significantly higher than those in blank control group (with P values below 0.05). The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in negative control+ TGF-β₁ group were significantly higher than those in negative control group (with P values below 0.05). The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in Smurf2 siRNA group were close to those in blank control group and negative control group (with P values above 0.05). The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in Smurf2 siRNA+ TGF-β₁ group were significantly lower than those in blank control+ TGF-β₁ group and negative control+ TGF-β₁ group (with P values below 0.05). Conclusions Silencing Smurf2 in human hypertrophic scar-derived fibroblasts can reduce the autocrine of TGF-β₁ and inhibit the TGF-β₁-induced α-SMA expression and collagen type Ⅰ synthesis.

Objective: To investigate the expression of SnoN in human hypertrophic scar fibroblasts and the mechanism of its participation in hypertrophic scar formation. Methods: Eight patients with hypertrophic scar after burn in need of surgery were admitted in our unit from January to October 2013, and then hypertrophic scar tissue and normal skin tissue of full-thickness skin donor site resected by surgery of the patients were collected. Hypertrophic scar fibroblasts and normal skin fibroblasts of patients were isolated with method of explant culture and then sub-cultured. Cells of the third to fifth passage were used in the following experiments. (1) The protein expressions of SnoN of hypertrophic scar fibroblasts and normal skin fibroblasts were assessed with Western blotting. (2) The mRNA expressions of SnoN of another batch of hypertrophic scar fibroblasts and normal skin fibroblasts were determined with reverse transcription polymerase chain reaction. (3) Another batch of hypertrophic scar fibroblasts and normal skin fibroblasts were treated with 10 ng/mL transforming growth factor beta1 (TGF-β₁) for 30 min, 1 h, 2 h, and 6 h, respectively, and then the protein expressions and mRNA expressions of SnoN of untreated cells and treated cells were detected as above. Data were processed with one way analysis of variance and independent sample t test. Results: (1) The protein expression of SnoN of hypertrophic scar fibroblasts was 0.020±0.003, significantly lower than that of normal skin fibroblasts (0.032±0.005, t=7.19, P<0.05). (2) The mRNA expression of SnoN of hypertrophic scar fibroblasts was 0.407±0.157, with no significant difference from that of normal skin fibroblasts (0.339±0.095, t=-1.29, P>0.05). (3) The protein expression of SnoN of normal skin fibroblasts was increased in a time-dependent fashion with the TGF-β₁ stimulation, and the protein expressions of SnoN of cells treated with TGF-β₁ for 30 min, 1 h, 2 h, and 6 h were significantly higher than those of untreated cells (with t values from 2.27 to 27.89, P values below 0.05). The protein expression of SnoN of hypertrophic scar fibroblasts was decreased in a time-dependent fashion with the TGF-β₁ stimulation, and the protein expressions of SnoN of cells treated with TGF-β₁ for 30 min, 1 h, 2 h, and 6 h were obviously lower than those of untreated cells (with t values from 10.80 to 13.85, P values below 0.05). (4) The mRNA expressions of SnoN of normal skin fibroblasts and hypertrophic scar fibroblasts were both increased in a time-dependent fashion with the TGF-β₁ stimulation, and the mRNA expressions of SnoN of the two types of cells treated with TGF-β₁ for 30 min, 1 h, 2 h, and 6 h were both significantly higher than those of untreated cells (with t values from 18.16 to 58.22, P values below 0.05). Conclusions The protein expression of SnoN in hypertrophic scar fibroblasts is reduced, which weakens its inhibitory effect on TGF-β₁ signal, thus amplifying the TGF-β₁ signal, and it may participate in the formation of hypertrophic scar.