Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Bacterial therapy has attracted increasing attention due to its special mechanism and abundant applications. With the flourishing development of synthetic biology, therapeutic genes have been introduced into engineering bacteria to improve their antitumor efficacy. However, it is difficult to spatiotemporally control the expression of these therapeutic genes at the tumor site in vivo, thereby considerably limiting the application of engineered bacteria in tumor treatment. To resolve this problem, we constructed a temperature-responsive bacterial strain capable of triggering the expression of exogenous genes in a laser-controllable way. Noxa, a pro-apoptotic protein, is chosen to test the expression of exogenous protein and its anti-tumor effect in engineered bacteria upon laser irradiation. Firstly, Noxa was fused to the C-terminus of the bacterial outer membrane protein cytolysin A (ClyA), and then the recombinant gene fragment ClyA-Noxa was inserted into the temperature-sensitive plasmid pBV220 and the recombinant plasmid was transformed into non-pathogenic Escherichia coli MG1655. Thus, we constructed the engineering strain (TRB@Noxa) that could express Noxa on the bacterial surface. TRB@Noxa could target and colonize the tumor tissue without causing notable host toxicity. The bacterial infection triggered thrombosis in the tumor tissue, resulting in the darkness of tumor sites. In a xenograft mouse tumor model, our strategy demonstrated precise tumor targeting and strong tumor inhibition. In conclusion, we successfully constructed a new engineering bacterial strain TRB@Noxa. TRB@Noxa combined with photothermal therapy could arrest tumor growth in the absence of photosensitizers, which represents an appealing method for antitumor therapy in the future.
Escherichia coli/radiation effects* ; Animals ; Humans ; Lasers ; Mice ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Neoplasms/therapy* ; Genetic Engineering ; Cell Line, Tumor ; Escherichia coli Proteins/genetics*

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Matrine has various pharmacological effects,including antitumor,anti-inflammatory,and antibacterial effects,which is an adjuvant drug widely used in clinical cancer chemotherapy.However,due to the fact that matrine is both an active and toxic component of Chinese materia medica,its clinical safety is particularly important.This article reviewed the research progress in the pharmacological effects of matrine from the aspects of anti-inflammatory,anticancer,antibacterial and antiviral,cardiovascular protection,neuroprotection,liver and kidney protection,and detoxification.It also summarized its toxicity and clinical application research,aiming to provide reference for the rational use of matrine.

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region.Methods:Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively.Results:511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective β-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment.Conclusion:Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

Objective To investigate the efficacy of hyperbaric oxygen (HBO) combined with recombinant human erythropoietin injection on neonatal hypoxic-ischemic encephalopathy (HIE),and the effects on the expression levels of cysteine aspartic protease-3 (caspase-3) and endogenous activin A (ACT A).Methods eventy-six child patients with HIE admitted to the Department of Pediatrics of the hospital from October 2015 to May 2017 were enrolled for the study,and were randomly divided into the observation group and the control group,each consisting of 38 patients.The patients in the control group received HBO therapy on the basis of conventional treatment,while the patients in the observation group had human erythropoietin injection in addition to the treatment received by the control group.After 10 days of treatment,treatment efficacy was evaluated for the 2 groups.After 5 and 10 days of treatment,the neonatal behavioral neurological assessment (NBNA) scores were evaluated,and nerve reflex recovery time and conscious recovery time for the patients of the 2 groups were recorded.The levels of serum caspase-3 and ACT A in the patients of the 2 groups were measured by enzyme-linked immunosorbent assay (ELISA),and adverse reactions of the two groups were recorded as well.Results Total efficacy rate for the observation group (89.47％)was significantly higher than that for the control group (71.05 ％) (P ＜ 0.05),After 5 and 10 days of treatment,the NBNA scores of the 2 groups were all significantly higher than those before treatment and the NBNA scores of the observation group were significantly higher than those before treatment,and the NBNA scores of the observation group were also obviously higher than those of the control group (P ＜ 0.05 or P ＜ 0.01).After treatment,the nerve reflex recovery time and conscious recovery time of the observation group were all shorter than those of the control group (P ＜ 0.05).After 5 days of treatment,the caspase-3 levels of the two groups were significantly higher than those before treatment,and that of the observation group was obviously lower than that of the control group (P ＜0.05).However,after 10 days of treatment,the caspase-3 levels in the 2 groups all decreased markedly,as compared with those after 5 days of treatment,and.that of the observation group was obviously lower than that of the control group (P ＜ 0.05).Conclusion HBO combined with recombinant human erythropoietin injection was superior to simple HBO therapy in the treatment of HIE,and could down-regulate the expression levels of Caspase-3 and ACT A,inhibit cell apoptosis,promote cell repair and ultimately lessen nerve damage.

Objective To investigate the efficacy of hyperbaric oxygen (HBO) combined with recombinant human erythropoietin injection on neonatal hypoxic-ischemic encephalopathy (HIE),and the effects on the expression levels of cysteine aspartic protease-3 (caspase-3) and endogenous activin A (ACT A).Methods eventy-six child patients with HIE admitted to the Department of Pediatrics of the hospital from October 2015 to May 2017 were enrolled for the study,and were randomly divided into the observation group and the control group,each consisting of 38 patients.The patients in the control group received HBO therapy on the basis of conventional treatment,while the patients in the observation group had human erythropoietin injection in addition to the treatment received by the control group.After 10 days of treatment,treatment efficacy was evaluated for the 2 groups.After 5 and 10 days of treatment,the neonatal behavioral neurological assessment (NBNA) scores were evaluated,and nerve reflex recovery time and conscious recovery time for the patients of the 2 groups were recorded.The levels of serum caspase-3 and ACT A in the patients of the 2 groups were measured by enzyme-linked immunosorbent assay (ELISA),and adverse reactions of the two groups were recorded as well.Results Total efficacy rate for the observation group (89.47％)was significantly higher than that for the control group (71.05 ％) (P ＜ 0.05),After 5 and 10 days of treatment,the NBNA scores of the 2 groups were all significantly higher than those before treatment and the NBNA scores of the observation group were significantly higher than those before treatment,and the NBNA scores of the observation group were also obviously higher than those of the control group (P ＜ 0.05 or P ＜ 0.01).After treatment,the nerve reflex recovery time and conscious recovery time of the observation group were all shorter than those of the control group (P ＜ 0.05).After 5 days of treatment,the caspase-3 levels of the two groups were significantly higher than those before treatment,and that of the observation group was obviously lower than that of the control group (P ＜0.05).However,after 10 days of treatment,the caspase-3 levels in the 2 groups all decreased markedly,as compared with those after 5 days of treatment,and.that of the observation group was obviously lower than that of the control group (P ＜ 0.05).Conclusion HBO combined with recombinant human erythropoietin injection was superior to simple HBO therapy in the treatment of HIE,and could down-regulate the expression levels of Caspase-3 and ACT A,inhibit cell apoptosis,promote cell repair and ultimately lessen nerve damage.

Objective To assess the clinical efficacy of perforators positioning technique in anterolateral thigh perforator sub lobe flap transplantation for reconstructing soft tissue defects of forearm or hand.Methods A retrospective case series study was performed to analyze 24 patients with forearm and hand soft tissue defects admitted from January 2013 to August 2017.There were 18 males and six females,aged 31-68 years (mean,52.3 years).The wound defect areas ranged from 11 cm × 10 cm to 18 cm× 14 cm.The anterolateral thigh sub lobe perforator flaps were used for repair.CT angiography (CTA) combined with color Doppler ultrasound (CDS) was used to determine the perforator position before operation.After the appropriate thigh side was selected according to the perforator position and the wound area,the lobed flaps were designed to ensure all the flaps for the stage I suture after the length was converted into width.All patients obtained stage Ⅱ repair,and the repair time was 5-29 days,with an average of 13 days.The accuracy of perforation positioning was observed during operation (the error was not more than 1 cm for accurate positioning).The flap survival and complications were recorded within 2 weeks after operation.Follow-up was performed using the seven indicators of flap function to evaluate the efficacy.Results The positioning accuracy rate was 99％.One case was seen necrosis about 2 cm at the proximal end of flap.Two cases had arterial crisis after flap operation and survived after active exploration.In two nonunion cases because of wound infection around the flap,one case was healed after dressing change,and another case was healed after debridement.The donor site of the flap obtained stage Ⅰ direct suture,and one case was seen obvious scar hyperplasia at the donor site.Flaps were made thinner in two patients with hand defects at the later stage.All 24 patients were followed up for 7-33 months,with an average of 18.3 months.According to the seven indexes of the flap function,the results were excellent in seven cases,good in 13,fair in three,and poor in onee,with an excellent and good rate of 83％.The flaps appeared soft with good color at the last follow-up.Conclusions In the treatment of soft tissue defects of forearm or hand using anterolateral thigh flap,conversion from length to width and direct suture of donor site can cover the wound well and reduce complications.Perforators positioning technique can facilitate precise preoperative planning and intraoperative accurate cutting.