Objective : To investigate the phenotype of amoxicillin ( AMX) unstable resistant Helicobacter pylori (Hp) evolving into AMX stable high level resistance and the detection of its mutated genes． Methods : Using the frozen Hp strain H390 as the starting strain，the clones resistant to AMX were continuously cultured on the medium with increasing AMX concentration，and the minimum inhibitory concentration ( MIC) of the resistant clones was detected．After frozen at －80 ℃ for 3 months，the drug resistance was stable according to whether the MIC de- creased after frozen storage． Genome sequencing analysis and efflux pump inhibition assay were performed on cloned H390r and parental strain H390 with the highest AMX MIC value，and gene mutations associated with the high level AMX resistance obtained by H390r were detected and identified. Results : Four AMX high level resistant clones were obtained by AMX screening with MICs of 12，32，64 and ≥ 256 mg / L ，respectively，and none of the MICs were altered after freezing at －80 ℃ . Compared to the parental strain H390，the AMX stable resistant clone H390r had mutations in several genes，including hefC encoding the RND efflux system，hopB and hopC encoding the pore proteins and ftsI encoding the penicillin binding protein ，which were associated with AMX resistance. H390r was substantially reduced in MIC to AMX in the presence of efflux pump inhibitors． Conclusion AMX can screen stable resistant clones from unstable resistant Hp．H390r had mutations in hefC，hopB，hopC，and ftsI asso- ciated with AMX resistance．These mutations may be the main reason why H390r acquired a stable high level of re- sistance to AMX.

【Objective】 To establish an information management platform for provincial rare blood group bank to achieve the interconnection and sharing of data such as rare blood group types, donor information and blood inventory, so as to enhance the supply security of rare blood group blood. 【Methods】 The information barriers of rare blood group management in each business link and among blood stations in Zhejiang province were analyzed using fishbone diagram. Data modeling technology was introduced based on the unified blood collection and supply business system and blood cloud platform of Zhejiang, the database view of rare blood group donors and rare blood group was constructed through demand analysis and model design, and a unified query platform was developed to achieve the sharing of rare blood group information. 【Results】 The system integrated, retrievaled and displayed rare blood type information, achieving the interconnection of information among various business links and blood stations within blood banks. Up to now, in addition to RhD negative blood group, there were 8 types of rare red blood cells in the bank, covering 7 blood group systems, 289 rare blood group donors and 216 units of frozen red blood cells of rare blood group. 【Conclusion】 The information system based on data modeling can improve the overall efficiency and collaboration of the system, and reduce the workload of system development and operation. It can provide reference for standardized data management and application, and also provide a model for establishing and improving of a national rare blood group information network.

Objective To analyze the effect of endoscopic tumor resection by submucosal tunnel(STER)on recurrence in patients with submucosal tumors(SMT)around cardia.Methods A total of 92 patients with SMT around cardia were selected and divided into the treatment group(n=46)and the control group(n=46)using random number table method.The treatment group and the control group were treated with STER and endoscopic submucosal dissection(ESD),respectively,and both groups were followed up for 12 months after surgery.Periop-erative indexes,therapeutic effects,quality of life,sleep,inflammatory indexes,immune indexes before and 1 week after surgery,complications 1 week after surgery,recurrence 12 months after surgery were compared between the two groups.Results Compared with the control group,the surgery time of the treatment group was longer,the hospital stay was shorter and treatment cost were lower,and the stripping speed was faster(P＜0.05).Compared with before surgery,scores of Pittsburgh sleep Quality index(PSQI),serum levels of interleukin-8(IL-8),inter-leukin-6(IL-6),high-sensitive C-reactive protein(hs-CRP)and whole blood levels of CD8+decreased in the two groups 1 week after surgery,and the levels were lower in the treatment group(P＜0.05).Compared with the preoperative results,the levels of whole blood CD4+and CD4+/CD8+,scores of Quality of Life Core 46 Questionnaire(QLQ-C46),Karnofsky Score(KPS)were higher in the two groups 1 week after surgery,those in the treatment group was higher(P＜0.05).1 week after surgery,the complication rate of the two groups was lower in the treat-ment group(P＜0.05),and 12 months after surgery,the recurrence rate of the two groups was not statistically significant(P＞0.05).Conclusion STER treatment for SMT around cardia was highly effective,resulting in superior perioperative outcomes,enhanced life and sleep quality,reduced systemic inflammation,and bolstered immune function.Moreover,it significantly lowered the risk of complications without raising the rates of recurrence.

Objective:To investigate the effects and mechanism of Jinlong Bushen Mixture against lipid metabolism disorders induced by high-sugar and high-fat diet in rats with metabolic syndrome by combining network pharmacology and experimental validation.Methods:TCMSP and related literature were retrieved to obtain the active components and targets of wolfberry, golden cherry, longan meat, jujube, gynostemma, rosmarinus officinalis, and motherwort in Jinlong Bushen Mixture, and GeneCards online database was retrieved to obtain metabolic syndrome-related targets. Venny 2.1.0 was used to obtain the intersection targets of Jinlong Bushen Mixture and metabolic syndrome, and STRING online STRING online database was used to construct the PPI network of intersecting targets. Core targets in the top 50 degree values were screened using the Cyto NCA plugin in Cytoscape 3.9.0. The DAVID Bioinformatics Resources 6.8 online analysis platform was used for GO functional enrichment and KEGG pathway enrichment analysis. Metabolic syndrome rat model was established using high sugar, high salt, and high fat feed for 20 weeks. The successfully modeling rats were divided into model groups, positive control group and Jinlong Bushen Mixture group according to random number table, and a blank control group was also set up, with 8 rats in each group. Jinlong Bushen Mixture group was gavaged with Jinlong Bushen Mixture 1.8 ml/kg, a positive control group was gavaged with Metformin 90 mg/kg, and the blank and model groups were gavaged with an equal volume of saline, 1 time/d, for 4 weeks. The changes in body weight, abdominal circumference, and fasting blood glucose in rats were observed. The blood lipid level in rats was detected. The pathological changes of liver tissues were detected by HE staining. The levels of ATP, IL-1β, and IL-6 in liver tissues were determined by ELISA. The mRNA expression of liver kinase B1 (LKB1), AMPK, Akt1, carnitine palmitoyltransferase 1A (CPT1A), and downregulated lactate dehydrogenase A (LDH-A) in liver tissue were detected by qRT-PCR. Western blot was used to determine the expression of p-LKB1, LKB1, p-AMPK, AMPK, p-Akt1, and Akt1 in liver tissue were detected by Western blotting.Results:A total of 141 main active components, 841 active targets, 18 763 metabolic syndrome targets, and 820 drug-disease intersection targets of Jinlong Bushen Mixture were obtained. The KEGG pathway enrichment analysis yielded 173 entries, including mainly the PI3K-Akt, and HIF-1 signalling pathway. The experimental results showed that the weight, fasting blood glucose, and lipid levels of rats in the Jinlong Bushen mixture group decreased, and the disorder of liver glucose and lipid metabolism in rats improved; the levels of ATP, IL-1β and IL-6 decreased ( P<0.05); The mRNA expression of LKB1, AMPK, Akt1, and CPT1A in liver tissue increased ( P<0.05), while LDH-A mRNA expression decreased ( P<0.05). The p-LKB1/LKB1, p-AMPK/AMPK, and p-Akt1/Akt1 ratio increased ( P<0.05). Conclusion:Jinlong Bushen Mixture may restore lipid metabolism disorders in the metabolic syndrome through multiple targets and pathways. Its mechanism may exert pharmacological effects through the LKB1/AMPK/Akt signaling pathway.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.

OBJECTIVE To investigate the effect of salidroside (Sal) on bone loss in obstructive sleep apnea syndrome(OSAS) rats by regulating the osteoprotegerin(OPG)/receptor activator of nuclear factor kappa-B ligand(RANKL) pathway. METHODS Rats were randomly divided into(12 rats/group) control group,OSAS group,Sal-L,Sal-M,and Sal-H groups(17.5,35,70 mg/kg). Except for the control group,all other groups were used to replicate the OSAS rat model through hypoxia and reoxygenation cycles. Bone density meters,three-point bending experiments,and Micro CT were applied to measure the bone density,biomechanics,and microstructural changes of the femur in rats. ELISA method was applied to detect serum levels of osteocalcin(BGP),alkaline phosphatase(ALP),and cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-I). RT-PCR was applied to detect OPG and RANKL mRNA levels in the femur. Western blotting was applied to detect the expression of OPG/RANKL pathway proteins in the femur. RESULTS Compared with the control group,the bone density,maximum intensity,maximum load,trabecular bone volume fraction(Tb.BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the OSAS group were decreased,the mRNA and protein expression of CTX-I and RANKL were increased(P<0.05). Compared with the OSAS group,the bone density,maximum intensity,maximum load,Tb.BV/TV,Tb.N,Tb.Th,BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the Sal-L,Sal-M,and Sal-H groups were increased sequentially,the mRNA and protein expression of CTX-I and RANKL were decreased sequentially,the above changes were most great in the Sal-H group(P<0.05). CONCLUSION Salidroside promotes bone formation and inhibits bone resorption by increasing OPG expression and decreasing RANKL expression,thereby reducing bone loss in OSAS rats.

Objective:The purpose of this study was to investigate the characteristics of distortion product otoacoustic emissions (DPOAE) in patients with auditory neuropathy (AN). The factors affecting DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate of first and last diagnosis in the natural course were analyzed.Methods:The sample was obtained from the Multicenter Study on Clinical Diagnosis and Intervention of AN (registration number: ChiCTR2100050125), and the diagnostic criteria for AN were based on the Chinese Clinical Practice Guidelines of Auditory Neuropathy (version 2022). Patients with bilateral AN who underwent 2 or more DPOAE tests were screened and divided into infant groups (≤3 years old) and non-infant groups (>3 years old) according to the age of detection, and the trend of DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate in the natural course of disease were analyzed, in order to explore the relevant influencing factors.Results:A total of 165 patients (330 ears) with AN were included in the study. The overall DPOAE elicitation rate per ear was 77.0%±29.4% at the initial diagnosis and 65.1%±35.2% at the final diagnosis, with a reduction observed in the elicitation rate of 171 ears (51.82%). In the infant group, there were 49 cases (98 ears), including 28 males and 21 females, whose found age ranged from 0 to 3 years old, with a median age of 0.7 years. DPOAE elicitation rate per ear was 57.9%±35.5% in the initial diagnosis, and 32.4%±32.1% in the final diagnosis, with a reduction observed in the elicitation rate of 69 ears (70.41%). In the non-infant group, there were 116 cases (232 ears), including 59 males and 57 females, ranging in found age from 3.9 to 40 years old, with a median age of 14 years old. DPOAE elicitation rate per ear was 84.6%±23.4% in the initial diagnosis, and 78.3%±27.1% in the final diagnosis, with a reduction observed in the elicitation rate of 102 ears (43.97%). Age was found to be correlated with DPOAE changes by multicategorical unordered logistic regression analysis ( B=-0.224, OR=0.799, P<0.001). Conclusions:The elicitation rate of DPOAE in AN patients decreases or even disappears with increasing disease duration; The rate of DPOAE extraction is found to be lower in infant patients with auditory neuropathy (AN) compared to non-infant AN patients. Additionally, it is observed that the decrease in DPOAE extraction rate is more pronounced in infant AN patients as the disease progressed, as compared to non-infant AN patients. DPOAE and cochlear microphonic potentials should be fully combined for accurate diagnosis, and regular follow-up should be conducted to understand the natural course of the disease and give personalized guidance and assistance.

Objective:To compare the differences between the variation interpretation standards and guidelines issued by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 (The 2015ACMG/AMP guideline) and the Deafness Specialist Group of the Clinical Genome Resource (ClinGen) in 2018 for hereditary hearing loss (Healing loss, HL) issued the expert specification of the variation interpretation guide (The 2018 HL-EP guideline) in evaluating the pathogenicity of OTOF gene variation in patients with auditory neuropathy. Methods:Thirty-eight auditory neuropathy patients with OTOF gene variant were selected as the study subjects (23 males and 15 females, aged 0.3-25.9 years). Using whole-genome sequencing, whole exome sequencing or target region sequencing (Panel) combined with Sanger sequencing, 38 cases were found to carry more than two OTOF mutation sites. A total of 59 candidate variants were independently interpreted based on the 2015 ACMG/AMP guideline and 2018 HL-EP guideline. Compared with the judgment results in 2015 ACMG/AMP guideline, the variants interpreted as lower pathogenic classifications in the 2018 HL-EP guideline were defined as downgraded variants, and the variants regarded as higher pathogenic classifications were defined as upgraded variants. Statistical analysis was conducted using SPSS 20.0. Results:The concordance rate of variant classification between the guidelines was 72.9%(43/59). The 13.6%(8/59) of variants were upgraded and 13.6% (8/59) of variants downgraded in the classifications of the 2018 HL-EP guideline. A couple of rules saw significant differences between the guidelines (PVS1, PM3, PP2, PP3 and PP5). The distribution of pathogenicity of splicing mutation was statistically different ( P=0.013). Conclusions:The 2018 HL-EP guideline is inconsistent with the 2015 ACMG/AMP guideline, when judging the pathogenicity of OTOF gene variants in patients with auditory neuropathy. Through the deletion and refinement of evidence and the breaking of solidification thinking, the 2018 HL-EP guideline makes the pathogenicity grading more traceable and improves the credibility.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.

Objective To observe the incidence and prognosis of respiratory failure in patients after cardiac surgery,and the risk factors were analyzed.Methods A total of 559 patients who underwent cardiac surgery were enrolled in Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from July 2020 to November 2023.Clinical data were extracted through the hospital information system(HIS).This included general data such as gender,age,body mass index(BMI),smoking history,alcohol history,comorbidities,and basic disease data like occurrence of respiratory tract infection in the past 1 month before surgery,preoperative use of antimicrobial drugs,ejection fraction,operation time,cardiopulmonary bypass time,intraoperative blood transfusion,nasogastric tube indwelling,nosocomial infection,secondary thoracotomy,preoperative white blood cell count(WBC),length of intensive care unit(ICU)stay,secondary intubation and tracheostomy,discharge diagnosis,and outcome.The patients were divided into two groups according to whether or not they had expiratory failure.The difference of the above data between the two groups was compared.Multivariate Logistic regression was used to analyze the risk factors of respiratory failure in patients after cardiac surgery,the prediction model was constructed based on the above risk factors,and the receiver operator characteristic curve(ROC curve)was drawn to analyze the predictive value of the prediction model for patients with respiratory failure.Results The incidence of respiratory failure in patients after cardiac surgery was 7.51%(42 cases).Multivariate Logistic regression analysis showed that intraoperative blood transfusion>2000 mL,nasogastric tube,and nosocomial infection were risk factors for respiratory failure in patients after cardiac surgery[odds ratio(OR)and 95%confidence interval(95%CI)were 4.136(1.794-9.535),3.162(1.454-6.878)and 3.488(1.262-9.638),all P<0.05].The ROC curve analysis showed that the prediction model had a certain predictive value for the occurrence of respiratory failure in patients after cardiac surgery[area under the curve(AUC)=0.738,95%CI was 0.658-0.818,P<0.001].The length of ICU stay of patients in the group with respiratory failure was significantly longer than that in the group without respiratory failure(hours:8.16±7.62 vs.4.52±3.95),the secondary intubation rate[80.95%(34/42)vs.0(0/517)]and the tracheostomy rate[88.10%(37/42)vs.0(0/517)]were significantly higher than those in the non-respiratory failure group,and the recovery/improvement rate was significantly lower than that in the non-respiratory failure group[59.52%(25/42)vs.90.13%(466/517)],the differences were statistically significant(all P<0.05).Conclusions Patients with intraoperative blood transfusion>2000 mL,nasogastric tube inserted,and nosocomial infection are the high-risk groups for respiratory failure after cardiac surgery.Medical staff should strengthen the identification of high-risk groups and actively take intervention measures to improve the prognosis of patients.