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.

Background In recent years, regional high-temperature weather in summer occurs frequently in China. Heat stroke is the most representative meteorological disease caused by high temperature. In order to improve monitoring, early warning, prevention, and control of heat stroke, it is of great significance to understand the epidemiological characteristics of heat stroke and the associated impact of heatwave. Objective To understand the epidemiological characteristics of heat stroke cases in Jinan City, and to explore the effects of heatwave exposure on heat stroke. Methods Case reports of heat stroke and daily data of meteorological factors in Jinan City from 2017 to 2022 were collected. We described the temporal, population, and regional distribution characteristics of heat stroke cases in Jinan City, and used a time-stratified case-crossover design combined with conditional logistic regression model to explore the effects of heatwave exposure on heat stroke under 12 heatwave definitions (different combinations of intensity and duration). The cut-off percentiles used for heatwave definitions were the 90th (P₉₀), 95th (P₉₅), 97.5th (P_97.5), and 99th (P₉₉) percentiles of daily mean temperature; the durations were ≥ 2 d, ≥ 3 d, and ≥ 4 d, respectively. P_i(k), where i is temperature threshold, and k is duration. For example, the definition of a heatwave was notated as P₉₀(2), indicating that the daily mean temperature is ≥ P₉₀ and lasts for ≥ 2 d. Alternatively, lag01 denotes the cumulative lag effect with a 1 d lag, and so on. Results A total of 1394 cases of heat stroke were reported in Jinan City from 2017 to 2022, including 581 mild cases and 813 severe cases, and 85 deaths were reported, with a cumulative fatality rate of 6.10%. The cases of heat stroke reported each year during the study period were concentrated from June to August and peaked in July (665 cases, 47.70%). The sex ratio of males to females in heat stroke cases was 2.02:1. A high incidence of heat stroke was in 50-89 years, with a smaller peak occurring in the age group of 50-59 years and a larger peak in the age group of 70-79 years, respectively. The high-incidence areas of heat stroke were distributed in the western part of Jinan City where city centers situated (Tianqiao District, 274 cases, 19.66%; Huaiyin District, 223 cases, 16.00%) and in the surrounding rural areas (Pingyin County, 254 cases, 18.22%). The effect of heatwave exposure on heat stroke was statistically significant during the study period. The largest effect estimates for the effect on heat stroke occurred under the heatwave definitions of P₉₉(2), P_97.5(3), and P_97.5(4) at lag04, lag03, and lag04, where corresponding OR (95%CI) values were 9.27 (4.71, 14.24), 8.95 (6.17, 12.98), and 8.22 (4.91, 13.78), respectively. The exposure-response curve showed that the risk of heat stroke tended to increase with the increase of average daily temperature. Conclusion July is the key period for the occurrence of heat stroke among Jinan City residents, while male cases are predominant, more serious cases, age concentration in the 50-89 years. The occurrence of heatwave can further increase the risk of heat stroke with a significant lag effect.

Objective:To investigate the application effect of problem-based learning (PBL) combined with scenario simulation in nursing teaching of needlestick injuries.Methods:A total of 123 undergraduates majoring in nursing were selected as research subjects from the classes of 2020 and 2021 in a medical university. The 60 undergraduates in the class of 2020 were established as control group and were given PBL teaching, and the 63 undergraduates in the class of 2021 were established as experimental group and were given PBL combined with scenario simulation. The two groups were compared in terms of theoretical score, skill examination score, and knowledge-attitude-practice (KAP) score of needlestick injury knowledge. SPSS 25.0 was used to perform the t-test, the chi-square test, and the rank sum test. Results:Compared with the control group, the experimental group had significantly higher scores of theoretical examination [(84.43±5.03) vs. (80.30±4.81), P<0.001] and skill examination [(88.40±4.26) vs. (83.55±5.84), P<0.001], as well as significantly higher scores of knowledge [(14.46±1.03) vs. (13.18±1.23), P<0.001], attitude [(52.59±3.09) vs. (48.05±3.06), P<0.001], and practice [(67.37±4.28) vs. (62.17±3.92), P<0.001] in KAP questionnaire. Conclusions:PBL combined with scenario simulation teaching can effectively improve the knowledge of protection against needlestick injuries and related skills in nursing students, enhance their awareness of needlestick injuries, and promote the protective behavior against needlestick injuries.

Objective:To investigate the application and effect of frontal-orbital reconstruction and distraction osteogenesis in the treatment of Crouzon syndrome using three-dimensiond reconstruction mold (3D-RM).Methods:Retrospective analysis was performed on the clinical data of children with Crouzon syndrome who were treated in the Department of Burning and Plastic Surgery, Children’s Hospital of Nanjing Medical University from January 2018 to December 2021. These children were divided into two groups. The study group performed fronto-orbital reconstruction combined with distraction osteogenesis using 3D-RM, while the control group performed the surgery without using 3D-RM. Intraoperative blood loss, operation time, duration of hospital stay, complication rate, cranial index, frontal and orbital retraction rate and postoperative frontal and orbital contour were compared between the two groups. The independent sample t-test was used to compare the differences in intraoperative blood loss, operation duration, hospital stay, postoperative cranial index and fronto-orbital retraction rate between the two groups. The Chi-square test was used to compare the differences in the incidence of postoperative complications between the two groups. Results:The study group included 10 children, including 6 males and 4 females, ranging in age from 9 to 37 months, with an average age of 19 months. In the control group, 8 children were included, including 5 males and 3 females, ranging in age from 8 to 46 months, with an average age of 25 months. The study group was followed up for 12 to 36 months, with an average of 18 months, and the head shape was better improved. The control group was followed up for 12 to 30 months, with an average of 18 months. No serious complications occurred and the head deformity was improved. There were no significant differences in intraoperative blood loss, operation duration, hospital stay, cranial index, fronto-orbital retraction rate and complication rate between the two groups (all P>0.05). The forehead shape of the study group was more symmetrical than that of the control group, the difference was statistically significant ( P<0.05). Conclusion:The effect of frontal orbital reconstruction and distraction osteogenesis using 3D-RM in the treatment of Crouzon syndrome is positive, the head shape and orbit are significantly improved. There were no serious complications after operation. It can play a good auxiliary role in the operation.

Objective:To investigate the application and effect of frontal-orbital reconstruction and distraction osteogenesis in the treatment of Crouzon syndrome using three-dimensiond reconstruction mold (3D-RM).Methods:Retrospective analysis was performed on the clinical data of children with Crouzon syndrome who were treated in the Department of Burning and Plastic Surgery, Children’s Hospital of Nanjing Medical University from January 2018 to December 2021. These children were divided into two groups. The study group performed fronto-orbital reconstruction combined with distraction osteogenesis using 3D-RM, while the control group performed the surgery without using 3D-RM. Intraoperative blood loss, operation time, duration of hospital stay, complication rate, cranial index, frontal and orbital retraction rate and postoperative frontal and orbital contour were compared between the two groups. The independent sample t-test was used to compare the differences in intraoperative blood loss, operation duration, hospital stay, postoperative cranial index and fronto-orbital retraction rate between the two groups. The Chi-square test was used to compare the differences in the incidence of postoperative complications between the two groups. Results:The study group included 10 children, including 6 males and 4 females, ranging in age from 9 to 37 months, with an average age of 19 months. In the control group, 8 children were included, including 5 males and 3 females, ranging in age from 8 to 46 months, with an average age of 25 months. The study group was followed up for 12 to 36 months, with an average of 18 months, and the head shape was better improved. The control group was followed up for 12 to 30 months, with an average of 18 months. No serious complications occurred and the head deformity was improved. There were no significant differences in intraoperative blood loss, operation duration, hospital stay, cranial index, fronto-orbital retraction rate and complication rate between the two groups (all P>0.05). The forehead shape of the study group was more symmetrical than that of the control group, the difference was statistically significant ( P<0.05). Conclusion:The effect of frontal orbital reconstruction and distraction osteogenesis using 3D-RM in the treatment of Crouzon syndrome is positive, the head shape and orbit are significantly improved. There were no serious complications after operation. It can play a good auxiliary role in the operation.

Objective:To investigate the safety and therapeutic effect of surgical resection combined with radiofrequency ablation on facial plexiform neurofibroma.Methods:The data of children with neurofibromatosis type Ⅰ treated by surgical excision combined with radiofrequency ablation in the Department of Burn and Plastic Surgery of Children’s Hospital of Nanjing Medical University from April 1, 2016 to April 1, 2020 was retrospectively analyzed. All patients were treated with partial tumor resection and radiofrequency ablation under general anesthesia. During the operation, the tumor body is gradually exposed through the hairline concealed incision. The tumor in the field of vision was removed to the maximum extent. Radiofrequency ablation was performed on distant tumor parts that was visible but inoperable, so as to achieve no residual tumor. Radiofrequency ablation was abandoned if intraoperative exploration revealed tumor invasion of facial nerve, deep fascia and orbit. The maximum output power of the radiofrequency ablation machine used during the operation was 200 W, and the exposed length of the electrode was 3 cm. The radio frequency machine could automatically adjust the power during the ablation process according to the impedance of the tissue to output the optimal energy, and monitor the temperature of the surrounding tissue in real time during the ablation process. The distal tumor body was located by B-ultrasound, penetrated, and ablated by radiofrequency needle. The amount of intraoperative bleeding was estimated, and the postoperative drainage volume, drainage tube placement time and complications were observed and analyzed. The facial nerve injury was evaluated at the time of discharge and the first month after operation. Six months after operation, the scar was evaluated with the patient scar assessment scale (PSAS) in the patient and observer scar assessment scale (POSAS). The measurement data of normal distribution was expressed as Mean±SD.Results:A total of 5 children were included, including 3 males and 2 females, aged from 1 year and 2 months to 6 years and 10 months. The tumors were all located in the facial area. The range of invasion was superficial muscle layer, and the postoperative pathology indicated plexiform neurofibroma. The incision length of 5 patients was (5.4±0.4) cm, the intraoperative bleeding volume was (36.0±4.9) ml, the postoperative drainage volume was (4.2±0.7) ml, and the drainage tube was placed for (2.4±0.5) days. No local infection or skin ulceration occurred after operation, and the body temperature did not fluctuate significantly. Follow-up time ranged from 12 months to 18 months, the median follow-up time was 12 months. At the time of discharge and one month after operation, there was no difficulty in eyebrow lifting in all the patients. In the early postoperative period, the swelling of the operation site was obvious, and the swelling gradually decreased after 40 days at the latest. One child developed local skin cyanosis, which gradually subsided one month after the operation after cold compress. It was considered that it was caused by local subcutaneous slight bleeding. The local scar after operation was slight and concealed, and the PSAS score of the children 6 months after operation was 27.2±4.4. During the follow-up period, the original tumor body was stable, and no progressive enlargement of tumor body was found.Conclusions:Surgical resection combined with radiofrequency ablation for facial plexiform neurofibroma is safe and effective. Compared with traditional surgery, it can reduce local injury and facial changes, and can be used as an auxiliary treatment, but it cannot completely replace the traditional surgery.

Objective:To investigate the effect of intrafrontal-orbital distraction osteogenesis in the treatment for school-aged children with severe proptosis in Crouzon syndrome.Methods:We retrospectively analyzed the clinical data of school-aged children with Crouzon syndrome treated with intrafrontal orbital distraction osteotomy at the Children’s Hospital of Nanjing Medical University from January 2016 to February 2021, and counted and analyzed the clinical results, complications (cerebrospinal fluid leakage, infection, etc.), and surgical safety.Results:A total of 12 children, 9 males and 3 females, aged 6-12.1 years, with an average age of 7.1 years, were included; 4 were cranial, 6 were craniofacial, and 2 were other types. All were shown with obvious proptosis. The surgical procedure was successful. Follow-up ranged from 3 to 20 months, with a mean of 14 months. The postoperative distraction distance was (19.1±3.3) mm, ranging from 15.2 to 25.6 mm. And the mean cranial index (CI) before and after surgery were 97.5% and 80.0%, respectively, with good craniofacial appearance and better improvement of proptosis and posterior cranial flattening. There were no other complications but for one child with infection at the external site of the distraction rod.Conclusions:The effect of frontal-orbital distraction osteotomy in the treatment of Crouzon syndrome with severe proptosis in school-aged children was positive, with significant improvement in proptosis and low incidence of postoperative cerebrospinal fluid leakage and infection. This procedure is a good choice for older children with severe proptosis.

Objective:To investigate the safety and therapeutic effect of surgical resection combined with radiofrequency ablation on facial plexiform neurofibroma.Methods:The data of children with neurofibromatosis type Ⅰ treated by surgical excision combined with radiofrequency ablation in the Department of Burn and Plastic Surgery of Children’s Hospital of Nanjing Medical University from April 1, 2016 to April 1, 2020 was retrospectively analyzed. All patients were treated with partial tumor resection and radiofrequency ablation under general anesthesia. During the operation, the tumor body is gradually exposed through the hairline concealed incision. The tumor in the field of vision was removed to the maximum extent. Radiofrequency ablation was performed on distant tumor parts that was visible but inoperable, so as to achieve no residual tumor. Radiofrequency ablation was abandoned if intraoperative exploration revealed tumor invasion of facial nerve, deep fascia and orbit. The maximum output power of the radiofrequency ablation machine used during the operation was 200 W, and the exposed length of the electrode was 3 cm. The radio frequency machine could automatically adjust the power during the ablation process according to the impedance of the tissue to output the optimal energy, and monitor the temperature of the surrounding tissue in real time during the ablation process. The distal tumor body was located by B-ultrasound, penetrated, and ablated by radiofrequency needle. The amount of intraoperative bleeding was estimated, and the postoperative drainage volume, drainage tube placement time and complications were observed and analyzed. The facial nerve injury was evaluated at the time of discharge and the first month after operation. Six months after operation, the scar was evaluated with the patient scar assessment scale (PSAS) in the patient and observer scar assessment scale (POSAS). The measurement data of normal distribution was expressed as Mean±SD.Results:A total of 5 children were included, including 3 males and 2 females, aged from 1 year and 2 months to 6 years and 10 months. The tumors were all located in the facial area. The range of invasion was superficial muscle layer, and the postoperative pathology indicated plexiform neurofibroma. The incision length of 5 patients was (5.4±0.4) cm, the intraoperative bleeding volume was (36.0±4.9) ml, the postoperative drainage volume was (4.2±0.7) ml, and the drainage tube was placed for (2.4±0.5) days. No local infection or skin ulceration occurred after operation, and the body temperature did not fluctuate significantly. Follow-up time ranged from 12 months to 18 months, the median follow-up time was 12 months. At the time of discharge and one month after operation, there was no difficulty in eyebrow lifting in all the patients. In the early postoperative period, the swelling of the operation site was obvious, and the swelling gradually decreased after 40 days at the latest. One child developed local skin cyanosis, which gradually subsided one month after the operation after cold compress. It was considered that it was caused by local subcutaneous slight bleeding. The local scar after operation was slight and concealed, and the PSAS score of the children 6 months after operation was 27.2±4.4. During the follow-up period, the original tumor body was stable, and no progressive enlargement of tumor body was found.Conclusions:Surgical resection combined with radiofrequency ablation for facial plexiform neurofibroma is safe and effective. Compared with traditional surgery, it can reduce local injury and facial changes, and can be used as an auxiliary treatment, but it cannot completely replace the traditional surgery.

Objective:To investigate the effect of intrafrontal-orbital distraction osteogenesis in the treatment for school-aged children with severe proptosis in Crouzon syndrome.Methods:We retrospectively analyzed the clinical data of school-aged children with Crouzon syndrome treated with intrafrontal orbital distraction osteotomy at the Children’s Hospital of Nanjing Medical University from January 2016 to February 2021, and counted and analyzed the clinical results, complications (cerebrospinal fluid leakage, infection, etc.), and surgical safety.Results:A total of 12 children, 9 males and 3 females, aged 6-12.1 years, with an average age of 7.1 years, were included; 4 were cranial, 6 were craniofacial, and 2 were other types. All were shown with obvious proptosis. The surgical procedure was successful. Follow-up ranged from 3 to 20 months, with a mean of 14 months. The postoperative distraction distance was (19.1±3.3) mm, ranging from 15.2 to 25.6 mm. And the mean cranial index (CI) before and after surgery were 97.5% and 80.0%, respectively, with good craniofacial appearance and better improvement of proptosis and posterior cranial flattening. There were no other complications but for one child with infection at the external site of the distraction rod.Conclusions:The effect of frontal-orbital distraction osteotomy in the treatment of Crouzon syndrome with severe proptosis in school-aged children was positive, with significant improvement in proptosis and low incidence of postoperative cerebrospinal fluid leakage and infection. This procedure is a good choice for older children with severe proptosis.

Objective:To investigate clinical effects of the three-dimensional(3D) digital technique-assisted distraction osteogenesis in newborns with Pierre Robin sequence(PRS).Methods:The data of neonatal Pierre Robin sequence treated with 3D digital technique-assisted distraction osteogenesis in Children’s Hospital Affiliated to Nanjing Medical University from April 2017 to April 2020 was retrospectively analyzed. 3D digital technique was used to assist the pre-operative design and osteotomy navigation template was made with 3D printing technique to guide in the mandibular osteotomy. CT scans were obtained 3 months postoperatively to follow up the growth of mandible. The rates of recurrence, titanium nail falling, infection, secondary operation and nerve injury were statistically analyzed. The counting data were analyzed using chi-square test. The independent influencing factors of postoperative complications were analyzed by multiple logistic regression, and the difference was statistically significant when P<0.05. Results:Three hundred and forty-five patients were included in the 3D digital technique group consisting of 215 males and 130 females with the ages ranged 3-28 days and the weights 1.8-3.2 kg. Surgical results were satisfied and very close to the preoperative design. Craniofacial CT results showed normal growth of mandible 3 months postoperatively. Three hundred and seventy-seven patients were included in the controlled group consisting of 230 males and 147 females with the ages ranged 6-28 days and the weights 1.6-3.6 kg. The recurrence rate, extender titanium nail off rate, reoperation rate and risk of nerve damage in the 3D digital technique group were 0.29%(1/345), 0.29%(1/345), 0.58% (2/345)and 0.29%(1/345), respectively, while in the control group, the numbers were 1.86%(7/377), 2.92%(11/377), 2.65%(10/377), 2.92% (11/377), respectively, which were significant lower than those in the 3D group. The infection rates were 7.83%(27/345) in the 3D digital technique group and 7.69%(29/377) in the control group, and there was no significant difference between the two groups. The results of multi-logistic regression analysis suggested that the 3D digital technique group could be an independent factor to reduce postoperative complications ( P=0.001). Conclusions:In the newborns with Pierre Robin sequence, 3D digital technique-assisted distraction osteogenesiscan significantly improve the accuracy and success rate of the operation and reduce the complication rate as well.