ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.
Flavonoids/metabolism* ; Fruit/genetics* ; Gene Expression Profiling/methods* ; Gene Expression Regulation, Plant ; Lycium/metabolism* ; Metabolic Networks and Pathways ; Transcriptome

Objective:To compare outcomes between standardized and misdiagnosis and mistreatment of osteosarcoma.Methods:A retrospective analysis of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (299 cases, control group) and those who were misdiagnosed (benign or infective) and received mistreatment (23 cases, study group) between January 2009 and December 2021. Gender, age, first operation mode, recurrence time, recurrence interval, metastasis time, metastasis interval, total survival time (months), survival status in the two group and tumor site reoperation mode in the study group were statistically analyzed. Further, chi-square test was performed for comparison of the clinical between two groups. The survival analysis was performed using Kaplan-Meier test and Log-rank test.Results:All the 322 patients were followed up. In the control group, the average follow-up time was 42 months (1-137 months), the average age was 24 years (3-80 years), male 184 cases, female 115 cases, and limb salvage rate was 85.3% (255/299). Seven patients underwent amputation, and the amputation rate was 17.7% (44/299). The recurrence rate was 8.4% (25/299), the average recurrence interval was 22.8 months (7-36 months), and the metastasis rate was 28.1% (85/299), the average metastasis time was 32.7 months (0-58 months). In the study group, the average of follow-up time was 30 months (9-117 months), the average age was 36 years (5-67 years), 17 males and 6 females. Among them, eleven patients were treated with limb salvage in the second stage, and the limb salvage rate was 47.8% (11/23). Seven patients underwent amputation, and the amputation rate was 30.4% (7/23). The recurrence rate was 26.1% (6/23), the average recurrence interval was 11 months (1-42 months), and the metastasis rate was 43.4% (10/23), the average metastasis time was 20.3 months (1-44 months). The 5-year survival rate was 50.7% in the study group and 56.1% in the control group. There was no significant difference between the two groups (χ 2=0.09, P=0.760). Conclusion:The overall prognosis of patients with high-grade osteosarcoma who receive active treatment after mistreatment is similar to that of patients with standardized treatment, but the recurrence and metastasis rate is higher, the recurrence time is earlier, and the amputation rate is higher.

ObjectiveTo evaluate the efficacy of Geriatric Nutritional Risk Index (GNRI) on admission on predicting neurological outcomes for stroke patients at the convalescence stage (three months after stroke). MethodsA total of 277 inpatients with ischemic stroke in Wenzhou TCM Hospital of Zhejiang Chinese Medical University from November, 2022 to January, 2023 were divided into good outcome group (n = 195) and poor outcome group (n = 82) according to the score of modified Rankin Scale (mRS) three months after stroke. Their clinical data and GNRI were compared. ResultsCompared with the good outcome group, the poor outcome group showed a lower level of GNRI (t = -9.569, P < 0.001), more proportion of patients with high nutritional risk (χ² = 68.861, P < 0.001). More cases with poor outcome were found with higher nutritional risk (Z = 65.406, P < 0.001). After covariate adjustment, higher level of GNRI was an independent protective factor for poor outcome three months after stroke (OR = 0.895, 95%CI 0.864 to 0.927, P < 0.05), and the OR increased with the nutritional risk grade of GNRI (P < 0.05). The area under the curve (AUC) of GNRI, score of NIHSS, and BMI were 0.812 (Z = 11.576, P < 0.001), 0.759 (Z = 8.328, P < 0.001), and 0.594 (Z = 2.716, P = 0.007), respectively; while the combination of GNRI and NIHSS was more effective (AUC = 0.875, Z = 17.389, P < 0.001). The sensitivities of GNRI, NIHSS and the combination of the two in predicting neurological function were 65.85%, 76.83% and 79.21%, respectively, and the specificities were 81.54%, 60.51% and 82.95%, respectively. ConclusionGNRI on admission is associated with neurological function three months after stroke. GNRI can be used alone or in combination with NIHSS score to predict neurological outcome in the rehabilitation period, which is a useful complement to traditional predictors.

Through the analysis of laws and policies related to registration self-inspection, visiting and researching enterprises, holding symposiums, and issuing nationwide questionnaires, the risks in the registration self-inspection process were summarized, analyzed, and evaluated. From the aspects of regulatory departments and manufacturing enterprises, we suggest to improve China's medical device registration regulations system and reduce the risks of all parties in the registration self-inspection work.
Risk Management ; Commerce ; Medical Device Legislation

Objective:To explore the efficacy of the proximal tibial lateral locking plate with rafting screws combined with Jail screws in the treatment of collapse fracture of the lateral tibial plateau.Methods:A retrospective case series study was performed on clinical data of 36 patients with collapse fracture of the lateral tibial plateau admitted to Suqian Hospital of Nanjing Drum Tower Hospital Group from January 2016 to January 2020, including 19 males and 17 females, aged 34-68 years [(48.6±5.8)years]. Schatzker classification was type II in 28 patients and type III in 8 patients. All patients were treated using the proximal tibial lateral locking plate with raft screws combined with Jail screws. The operation time, intraoperative blood loss and fracture healing were detected. The distance of articular surface collapse of the tibial plateau, posterior inclination angle (PSA) of the tibial plateau, tibial plateau varus angle (TPVA) and Rasmussen anatomical score were compared before operation and at day 2 and 1 year after operation. The Hospital for Special Surgery (HSS) score was used to evaluate knee function at day 2 and 1 year after operation. Complications were also recorded.Results:All patients were followed up for 12-32 months [(19.5±3.1)months]. The operation time was 56-82 minutes [(68.5±9.1)minutes]. The intraoperative blood loss was 40-100 ml [(75.6±10.2)ml]. The fracture was clinically healed by first-stage, with the healing time of 8 to 15 weeks [(12.5±1.3)weeks]. The distance of articular surface collapse of the tibial plateau was improved from (15.5±4.2)mm before operation to (0.7±0.3)mm at day 2 after operation and (1.0±0.2)mm at 1 year after operation (all P<0.01). The PSA was improved from (21.2±2.1)° before operation to (8.9±0.8)° at day 2 after operation and (9.2±0.6)° at 1 year after operation (all P<0.01). The TPA was improved from (100.2±3.7)° before operation to (88.9±1.8)° at day 2 after operation and (87.2±1.6)° at 1 year after operation (all P<0.05). The Rasmussen anatomical score changed from (7.8±1.8)points before operation to (17.1±0.9)points at day 2 after operation and (16.3±0.7)points at 1 year after operation (all P<0.01). There were no significant difference in the distance of articular surface collapse of the tibial plateau, PSA, TPVA and Rasmussen anatomical score at day 2 and 1 year after operation (all P>0.05). The HSS score was (92.8±3.2)points at 1 year after operation, significantly higher than (74.8±3.5) points at day 2 after operation ( P<0.01). Two patients sustained superficial wound infection after operation, which healed after debridement and dressing change. No deep infection occurred. Conclusion:For patients with collapse fracture of the lateral tibial plateau, the proximal tibial lateral locking plate with rafting screws combined with Jail screws can effectively prevent secondary collapse of the articular surface and obtain satisfactory anatomical reduction, good functional recovery and few postoperative complications.

Objective:To evaluate our novel path based on anatomical division of the anterior lateral wall of calcaneus and the sustentaculum tali for precise sustentacular screw placement in the surgical treatment of calcaneal fractures of Sanders types Ⅱ and Ⅲ.Methods:The anterior lateral wall of the calcaneus was divided into the anterior-superior zone S 1, the anterior-inferior zone S 2, the posterior-superior zone S 3 and the posterior-inferior zone S 4 for demarcation of the screw insertion points by our method of Four Zones, and into the front, middle and rear sections by our method of Three Sections for demarcation of the screw target points. The specimens were scanned by CT and modeled by Mimics. On the 3D virtual model of the calcaneus, one screw was placed from each zone of the anterior lateral wall of the calcaneus to the sustentaculum tali body. The screw placement target for S 1 and S 2 was the medial intersection point P 1 of the front and middle sections of the sustentaculum tali, and that for S 3 and S 4 was the medial intersection point P 2 of the middle and rear sections of the sustentaculum tali. It was observed whether the screws were placed in the bone channel. A total of 72 patients were included who had been admitted to Department of Orthopaedics, Suqian Hospital Affiliated to Xuzhou Medical University for calcaneal fractures of Sanders types Ⅱ and Ⅲ from January 2017 to January 2021. They were divided into an anatomical division group and a 3D printing group according to their screw placement method for the sustentaculum tali. In the anatomical division group of 32 patients subjected to screw placement based on our anatomical division, there were 25 males and 7 females, aged from 24 to 60 years; in the 3D printing group of 40 patients subjected to screw placement assisted by 3D printing, there were 31 males and 9 females, aged from 25 to 58 years. The disparities between the parameters of sustentacular screw placement and the actual values were compared in the anatomical division group, and the total number of screws, screws on average, distribution of screws, and accuracy of screw placement were compared between the 2 groups. Results:All the screws which were virtually placed in the specimens of the calcaneus from S 1 and S 2 to P 1 and from S 3 and S 4 to P 2 passed through the bony channel, with no perforation into the tarsal sinus. There was no significant difference in the general date between the anatomical division group and the 3D printing group, showing they were comparable ( P > 0.05). In the anatomical division group, a total of 52 screws were placed to the sustentaculum tali with an average of (1.63 ± 0.48) screws per patient, and 2 screws were placed in 20 patients, yielding an accuracy rate of screw placement of 92.3% (48/52). There were no statistically significant differences between the parameters and the actual values of screw placement in the anatomical division group ( P > 0.05). In the 3D printing group, a total of 63 screws were placed to the sustentaculum tali with an average of (1.58 ± 0.49) screws per patient, and 2 screws were placed in 23 patients, yielding an accuracy rate of screw placement of 93.7% (59/63). There were no significant differences in the above comparisons between the anatomical division group and the 3D printing group ( P > 0.05). Conclusion:In the surgical treatment of calcaneal fractures of Sanders types Ⅱ and Ⅲ, the sustentacular screw placement based on our anatomical division of the anterior lateral wall of the calcaneus and the sustentaculum tali can lead to similar clinical accuracy as 3D printing-assisted screw placement does.

Objective:To compare the clinical effects of minimally invasive reduction through a bone tunnel combined with Jail screwing and those of posterolateral locking plating in the treatment of simple posterolateral tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 48 patients who had been operatively treated and completely followed up at Department of Orthopedics, Suqian Hospital of Nanjing Drum Tower Hospital Group for simple posterolateral tibial plateau fractures from October 2016 to October 2020. There were 26 males and 22 females, aged from 35 to 68 years. They were divided into a minimally invasive group (25 cases subjected to minimally invasive reduction through a bone tunnel combined with Jail screwing) and an incision group (23 cases subjected to posterolateral locking plating) according to their surgical methods. The operation time, incision length, intraoperative blood loss, fracture healing time, cumulative fluoroscopy time, hospital stay and posterior inclination angles of the tibial plateau and Hospital for Special Surgery (HSS) knee function scores at 1, 3, 6, 9, and 12 months after operation were compared between the 2 groups. Complications in the 2 groups of patients were recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The 48 patients were followed up for 12 to 36 months (average 16.5 months). The minimally invasive group was significantly better than the incision group in operation time [(42.6±9.1) min versus (65.7±11.5) min], incision length [(4.0±0.4) cm versus (15.0±1.5) cm], intraoperative blood loss[(22.6±5.8) mL versus (31.5±8.8) mL], hospital stay [(7.6±1.4) d versus (11.1±2.4) d], and HSS score one month after operation [(84.8±1.9) points versus (72.9±4.1) points], but the cumulative fluoroscopy time in the incision group [(4.1±1.4) s]was significantly less than that in the minimally invasive group [(22.3±4.2) s] ( P<0.05). There were no significant differences in fracture healing time, HSS scores at 3, 6, 9, or 12 months after operation, or posterior inclination angle of the tibial plateau between the 2 groups ( P>0.05). There were no such complications as wound infection, vascular injury, internal fixation failure, nonunion or malunion of fractures in either of the 2 groups. Two cases in the incision group presented with symptoms of common peroneal nerve injury but recovered 3 months after operation. Conclusions:Although both minimally invasive reduction through a bone tunnel combined with Jail screwing and posterolateral locking plating can achieve satisfactory outcomes in the treatment of simple posterolateral tibial plateau fractures, the minimally invasive technique is preferable because it shows the advantages of a smaller incision, less bleeding, shorter operation time, a lower operation risk, quicker postoperative recovery and shorter hospital stay.

Objective:To analyze the distribution and antimicrobial resistance pattern of bacteria isolated from alveolar lavage fluid in pediatric patients with lower respiratory tract infection from 2016 to 2018.Methods:The alveolar lavage fluid of pediatric patients aged <18 years old with lower respiratory tract infection in ten hospitals from January 2016 to December 2018 were collected, and the pathogenic bacteria were cultured and isolated. The paper diffusion method or minimum inhibitory concentration method was used to conduct drug susceptibility tests for the isolated strains.The distribution of pathogenic bacteria and the source department of the strains were analyzed.Chi-sqare test was used for statistical analysis.Results:Of 1 271 isolates, 606 strains (47.7%) were gram-negative bacteria, 628 strains (49.4%) were gram-positive bacteria, and 37 strains (2.9%) were fungi. The common pathogens were Streptococcus pneumoniae (36.7%, 466/1 271), Acinetobacter baumannii (16.8%, 214/1 271), Staphylococcus aureus (12.7%, 162/1 271), Klebsiella pneumoniae (8.3%, 105/1 271), Haemophilus influenzae (7.4%, 94/1 271), Pseudomonas aeruginosa (6.2%, 79/1 271), Burkholderia cepacia (5.3%, 67/1 271) and Escherichia coli (3.7%, 47/1 271). The main pathogens in the intensive care unit (ICU) were gram-negative bacteria (80.1%, 428/534), among which Acinetobacter baumannii was the most common (3.7%, 199/534). The main pathogens in the non-ICU were gram-positive bacteria (70.8%, 522/737). The detection rates of methicillin-resistant Staphylococcus aureus (MRSA) were 45.1%(23/51) in the ICU and 43.2% (48/111) in the non-ICU, respectively. The detection rates of penicillin-resistant Streptococcus pneumoniae (PRSP) were 10.9%(6/55) in the ICU and 18.5% (76/411) in the non-ICU, respectively. The detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP) were 57.3%(43/75) in the ICU and 33.3%(10/30) in the non-ICU, respectively. The detection rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in the ICU was higher than that in the non-ICU (49.1%(27/55) vs 25.0%(6/24)), and the difference was statistically significant ( χ2=3.98, P=0.046). Eight strains (17.0%) of carbapenem-resistant Escherichia coli were detected, and 164 strains(76.6%) of carbapenem-resistant Acinetobacter baumannii were detected. Seventy-eight Haemophilus influenzae isolates were isolated from non-ICU, and the resistance rate to ampicillin was 57.4%(54/94). Burkholderia cepacia isolates were all isolated from ICU, and the resistance rates to piperacillin-tazobactam, levofloxacin, ciprofloxacin and compound sulfamethoxazole were 13.4%(9/67), 3.0%(2/67), 0(0/67) and 9.0%(6/67), respectively. Conclusions:Streptococcus pneumoniae is still the most common pathogen in pediatric patients with lower respiratory tract infection. Gram-negative bacilli are the main pathogens in pediatric patients with lower respiratory tract infection in the ICU. The dection rates of MRSA, PRSP and carbopenem-resistant gram-negative bacilli are high. And the resistance rate of Haemophilus influenzae to ampicillin is also high. The clinical empirical treatment should be determined according to different clinical background.

Objective To investigate the indications of optic canal decompression in the patients with front-orbital fibrous dysplasia and the methods of intraoperative optic canal localization and decompression. Methods We collected 30 cases of fibrous dysplasia. All patients had sufficient images assessment. Patients with symptoms underwent surgery, including front-orbital cranioplasty and optic canal decompression. The frontotemporal epidural approaches were used. If there was a proptosis, the approach was extended with the removal of superior orbital ridge. Six patients undertook intraoperative CT and MRI fusion navigation, assisting in confirming the trunk, orbital and cranial orifice of optic nerve. During the operation, the optic canals were decompressed by three-bits method, to confirm the position of optic nerve. Results There were 30 cases of optic canal decompression and one case of vision loss. The visual acuity and vision field of the remaining patients improved to varying degrees. The proptosis disappeared or alleviated after the operation. Thirteen cases were reconstructed with normal internal plate, five cases with titanium plate, nine cases without reconstruction, and two cases were paved with proliferative broken bone on the orbital top; one case recurred with exophthalmos again after five years, but the visual acuity did not decline. Conclusion For the patients with front-orbital fibrous dysplasia, active surgical treatment should be taken, optic canal decompression should be chosen for diminution of vision, craniofacial anaplasty and orbital decompression should be performed in patients with facial deformity. The epidural approach is a good option to locate the optic nerve from the orbital orifice or cranial orifice. Combined with the three-bits method, we can achieve safe and meticulous optic nerve decompression.