Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To explore the feasibility and advantages and disadvantages of local anesthesia for TiRobot-assisted removal of sacroiliac screws by comparison with general anesthesia for TiRobot-assisted removal of sacroiliac screws.Methods:A retrospective study was performed in 39 patients with posterior pelvic ring fracture-dislocation who had undergone removal of percutaneous sacroiliac screws after fracture union from January 2017 to December 2020 at Department of Orthopaedic Surgery, Hospital Affiliated to Chengdu University. Their sacroiliac screws were removed with TiRobot assistance under local anesthesia (LA group) or general anesthesia (GA group). In the LA group of 18 cases, there were 10 males and 8 females, aged (43.3 ± 8.4) years (from 25 to 58 years); in the GA group of 21 cases, there were 12 males and 9 females, aged (44.9 ± 9.0) years (from 23 to 60 years). The 2 groups were compared in terms of time for planning screw removal path, fluoroscopy frequency, fluoroscopy time, operation time, anesthesia time, anesthesia cost, postoperative visual analogue scale (VAS) and postoperative ambulation time.Results:There was no statistically significant difference in baseline data between the 2 groups, showing comparability ( P>0.05). Follow-ups revealed grade A wound healing in all patients. There were no significant differences between the 2 groups in time for planning screw removal path, fluoroscopy frequency, fluoroscopy time or operation time ( P>0.05). The anesthesia time [(41.6 ± 8.3) min], anesthesia cost [(653.5 ± 102.6) yuan] and postoperative ambulation time [(2.6 ± 0.6) h] in the LA group were significantly less than those in the GA group [(52.3 ± 9.5) min, (2,475.6 ± 261.8) yuan and (8.7 ± 2.4) h] while the VAS score in the former group (3.8 ± 1.5) was significantly higher than that in the latter group (2.5 ± 1.3) (all P<0.05). Conclusions:It is feasible to use local anesthesia for TiRobot-assisted removal of sacroiliac screws. In TiRobot-assisted removal of sacroiliac screws, compared with general anesthesia, local anesthesia may lead to shorter anesthesia time, lower anesthesia cast and shorter ambulation time, but the patients need to be compliant enough.

Objective:To investigate the therapeutic effect of exosomes divided from bone marrow mesenchymal stem cell (BMSC) on pancreatic cancer in vivo through regulation of tumor-associated macrophages (TAM) polarization.Methods:Ten male C57BL/6 mice weighing approximately 20 g, ages 4 weeks, were used for BMSC exosomes extraction and PKH26 labelling. Thirty female SPF BALB/c-nu/nu nude mice weighing approximately (18.56±0.85) g, ages 4-6 weeks, were adopted for pancreatic carcinoma models. The models were randomly divided into 3 groups with 10 in each: control group (injected with PBS through tail vein), portal vein treatment group (injected with exosomes in PBS through portal vein), tail vein treatment group (injected with exosomes in PBS through tail vein). After the models were executive 8 weeks later, the percentage of PKH26 positive-exosomes in pancreas tissue was quantified by flow cytometry technique. The volume of the primary pancreatic tumor, the tumor volume of inhibitory rate, the number of metastatic nodule, and the ascitic fluid were assess. Also, the weight of liver and the tumor weight were evaluated. The expression of M1 and M2 macrophage-activate biomarkers and the content of pancreatic cancer marker B7-H4 tumor carbohydrate antigen 199 in peripheral blood was detected. Moreover, the expression of Survivin and matrix metalloproteinase-9 (MMP-9) in pancreatic cancer tissue cells was also detected.Results:There was no significant difference for the tumor volume of inhibitory rate between portal vein treatment group (72.4±21.6)% and tail vein treatment group (70.1±20.7)% ( t=0.24, P=0.811). Compared with control group, the volume of the primary pancreatic tumor, the weight of liver, the tumor weight, the number and rate of liver metastatic nodule, the ascitic fluid, and the number of other metastatic nodule were totally lower in the 2 treatment groups with significant difference (all P<0.05). Compared with the control group, iNOS and CD68 in portal vein treatment group and tail vein treatment group were increased, while Arginase, CD206, B7-H4, tumor carbohydrate antigen 199, Survivin and matrix metalloprotein-9 were decreased, with statistically significant differences (all P<0.05). Conclusion:Exosomes derived from BMSC can inhibit the polarization of TAM to the M2 phenotype and induce their polarization to the M1 phenotype, thereby suppressing the proliferation, invasion and migration of pancreatic cancer.

OBJECTIVE：To investigate the efficacy of hormone combined with cyclophosphamide in the treatment of connective tissue disease-associated interstitial lung disease （CTD-ILD）and to analyze its influential factors. METHODS ：100 patients diagnosed as CTD-ILD in our hospital from Jan. 2018 to Jan. 2019 were randomly divided into observation group and control group ，with 50 cases in each group. Control group was treated with Compound cyclophosphamide tablets ，50 mg each time，3-4 times each day. Observation group was additionally treated with Prednisone acetate tablets ，10 mg each time ，3-4 times each day ，on the basis of control group. Treatment courses of 2 groups lasted for 6 months. The clinical efficacy ，the occurrence of ADR，lung function before and after treatment ，the levels of peripheral IL- 6，CRP and PCT and quality of life （SGRQ score ）were compared between 2 groups. According to the therapeutic efficacy ，all patients were divided into effective group and ineffective group. The related factors influencing the clinical efficacy of CTD-ILD were analyzed by univariate and multivariate Logistic regression analysis. RESULTS ：After treatment ，total response rate ，FVC，FEV1 and DLCO of observation group were significantly higher than those of control group ，while SGRQ score ，levels of IL- 6，CRP and PCT in peripheral blood were significantly lower than control group （P＜0.05）. There was no significant difference in the total incidence of ADR between 2 groups（P＞0.05）. Univariate analysis showed that there were no significant differences in gender ，age，past medical history and CTD type between effective group and ineffective group （P＞0.05）. However ，there were statistical significancant differences in the distribution of different levels of IL- 6，CRP and PCT in peripheral blood between 2 groups（P＜0.05）. Multivariate Logistic regression analysis showed that IL- 6 was an independent risk factor for therapeutic efficacy of combined therapy [OR （95％CI）＝ 4.537（3.668，10.352），P＝0.002]. CONCLUSIONS ：Hormone combined with cyclophosphamide can significantly improve the therapeutic efficacy of CTD-ILD patients ，improve their lung function and quality of life ，and reduce the expression level of inflammatory factors. The level of IL- 6 is an independent risk factor affecting the efficacy of the treatment ，and its changes should be paid close attention to during the treatment.

Objective:To analyze the clinical, genetic characteristics and follow-up data of Chinese patients with hypophosphatasia (HPP).Methods:A retrospective analysis was conducted on six children with HPP admitted to the Department of Endocrinology, Genetics and Metabolism in Beijing Children′s Hospital from October 2010 to January 2019. Summarized the clinical and follow-up data of all six patients, as well as the pathogenic variants of five children.Results:The serum alkaline phosphatase levels of all six children (five males and one female) were significantly reduced (2-49 U/L). The 6 patients aged from 2 months to 6 years and 4 months, 4 infantile HPP, 1 childhood HIP and 1 odonto HPP. The four patients with infantile HPP presented with anorexia, slow weight gain and hypercalcemia, whereas the one patient with childhood HPP and the other patient with odonto HPP had tooth loss. The patient with childhood HPP also manifested with motor dysfunction. Genetic testing was conducted for five patients and 4 unrelated Chinese families and revealed 10 variations in ALPL gene, including 7 missense variation, 1 insertion variation, 1 frameshift variation, 1 deletion variation.Of which 3 were novel (p.Y28C, p.268, F>L, p.A176V).One of the infantile patients lost follow-up and the other three deceased. The clinical conditions were much improved with medical intervention for patients with childhood, orodonto HPP.Conclusions:While HPP patients with different ages of onset present with common features, the prognosis differ significantly. The prognosis is good for patients with childhood, orodonto HPP and poor for patients with infantile HPP. Genetic testing is the main method for definitive diagnosis.

Objective:To investigate the clinical and genetic features, and treatment of X-linked hypophosphatemic rickets (XLH).Methods:In this retrospective study, we reviewed the medical records of 25 pediatric patients with XLH who were admitted to Department of Endocrinology Genetics and Metabolism,Beijing Children′s Hospital from January 2010 to January 2020. The clinical characteristics, PHEX gene variants, as well as clinical outcome of the patients were summarized. To analyze the correlation between genotype and phenotype, the patients were divided into different subgroups according to the location of the variants, including N-terminal-located vs. C-terminal-located variant, and Zn-binding domain exon 17 or 19 variant vs. non-exon 17 or 19 variant. The age at onset, height standard deviation score (HtSDS), intercondylar or intermalleolar distance, fasting serum phosphorus, and HtSDS and intercondylar or intermalleolar distance at the final follow-up were compared by rank sum test or t text. Results:Among the 25 children with XLH, 8 were boys and 17 were girls. The median age of onset was 1.2 (1.0, 1.8) years, and the median age of diagnosis was 2.5 (1.5, 4.3) years. The main clinical manifestations were abnormal gait and lower limb deformity. The HtSDS was -2.0(-3.2, -0.8), and the intercondylar or intermalleolar distance was 4.5 (3.0, 6.0) cm. The fasting serum phosphorus level was 0.8 (0.7, 0.9) mmol/L, while the serum alkaline phosphatase level was (721±41) U/L and the serum calcium level was (2.5±0.1) mmol/L. Three patients (12%) had parathyroid hormone levels above the upper limit of the normal range. Twenty-five patients (100%) showed radiographic changes of active rickets. Nephrocalcinosis was found in 2 cases (9%). Twenty-four different PHEX variations were detected in 25 patients, among whom 11 (44%) had not been reported previously. No hot spot variation was found. No statistical differences (all P>0.05) were identified in clinical features and outcomes either in comparing patients with N-terminal (21 cases) and C-terminal (4 cases) variants, or in comparing patients with variant located in exon 17 or 19 (4 cases) or not (21 cases). Twenty-four cases (96%) were treated regularly with phosphate supplements and active vitamin D. After 2.7 (1.6, 5.0) years of follow-up, clinical symptoms were relieved in 96% (24/25) of the patients. The HtSDS after treatment had no significant difference compared to that before treatment (-2.0(-3.2, -0.8) vs.-2.0(-2.8, -1.1), Z =-0.156, P>0.05), while the intercondylar or intermalleolar distance after treatment was significantly reduced compared to that before treatment (4.5(3.0, 6.0) vs. 1.5(0, 3.3) cm, Z =-3.043, P<0.05). Bone X-rays were reexamined in 17 cases after treatment, and radiographic signs of rickets were improved. Eighteen cases had secondary hyperparathyroidism and 7 cases had nephrocalcinosis. Conclusions:The main clinical manifestations of XLH are abnormal gait, lower limb deformity and short stature. A high proportion of novel variations of PHEX gene but no hot spot variation neither genotype-phenotype correlation are found. Regular treatment with phosphate supplements and active vitamin D can significantly improve the symptoms except for the height. However, the rate of adverse events including secondary hyperparathyroidism and nephrocalcinosis seems to be high.

Objective To evaluate the factors related to contralateral hip fracture in the elderly patients with hip fracture by meta analysis.Methods Pubmed,Cochrane,CBMdisc,CNKI Chinese Journal Full Text Database and Wan Fang Database were searched for publications at home and abroad from January 2005 to April 2018 on factors related to contralateral hip fracture after hip fractures in the elderly.The publication quality was strictly evaluated before the data were extracted concerning gender and age(＞ 65years) of the patients,concomitant osteoporosis (Singh sign ≥ 4),primary fracture type,concomitant Parkinson disease,concomitant stroke,concomitant senile dementia,concomitant cataract,concomitant rheumatoid arthritis,concomitant diabetes,type of internal fixation for primary fracture and therapeutic compliance.Revman5.0 was used to perform the statistical analysis and the OR value and 95％ CI were calculated fore each index.Results A total of 17 studies were included involving 1,504 patients with contralateral hip fracture among 13,717 elderly patients with hip fracture.The factors related to the refracture of the contralateral hip were the age of the patients (OR ＝-3.55,95％ CI:-5.60 ～-1.50,P ＜ 0.001),osteoporosis (OR=2.38,95％CI:1.36～4.17,P=0.002),Parkinson disease (OR=4.54,95％CI:2.74～7.53,P ＜0.001),stroke (OR=0.33,95％ C I:0.18～0.59,P ＜ 0.001),senile dementia (OR=0.43,95％CI:0.29～0.62,P ＜0.001),cataract (OR=0.37,95％CI:0.22～0.63,P ＜0.001),rheumatoid arthritis (OR =0.32,95％ CI:0.21 ～ 0.50,P ＜ 0.001),diabetes (OR =0.65,95％ CI:0.47～0.91,P=0.01),type of internal fixation for primary fracture (OR=0.51,95％ CI:0.30 ～ 0.85,P =0.01),and therapeutic compliance (OR =0.36,95％ CI:0.21 ～ 0.64,P ＜ 0.001).However,the refracture of the contralateral hip was not related to gender (OR =1.07,95％ CI:0.45 ～2.56,P=0.88),smoking (OR=0.86,95％CI:0.40～1.86,P=0.70),fracture type (OR=0.97,95％ CI:0.60～1.57,P=0.90),or hypertension (OR=0.70,95％ C I:0.41～1.21,P=0.20).Conclusions In elderly patients with hip fracture,the risks for contralateral hip fracture may be advanced age,concomitant osteoporosis,Parkinson disease,stroke,senile dementia,cataract,rheumatoid arthritis and diabetes,type of internal fixation for primary fracture,and poor therapeutic compliance.However,no sufficient evidence has suggested that gender,smoking,type of hip fracture or concomitant hypertension might be associated with the contralateral hip fracture.

Objective To analyze the effect of the fracture healing by using selective sensory radicotomy before and after the ganglion.Methods From September,2014 to August,2015,120 rats were averagely divided into 3 groups,which was the sham operate group(SO),the anterior injury of ganglion rhizotomy group (AGR) and the posterior injury of ganglion rhizotomy group (PGR).Tibial transverse fracture was performed on right or left randomly and the fracture was fixed with intramedullary.In coordination with the fractured-side,the selective radicotomy from L4 to L6 was made.The mRNA level of collagen-Ⅰ and collagen-Ⅱ in bony callus was quantified at 3,7 days and 2 weeks after the operation by RT-PCR(n=5).The histological examination,X-ray,biomechanical testing were performed at 4 and 8 weeks.The quantitative data of iconography and biomechanics was acquired by using the relative ration which resulted from fractured-side data dividing the unfractured-side one for every pair tibia in same rat.Results At 3 days after surgery,the mRNA of collagen-Ⅰ were 81.3±11.1,37.5±8.2 and 24.7±9.2,the mRNA of collagen-Ⅱ were 2.4±0.5,2.1±1.0 and 2.9±1.2 in SO,AGR and PGR group respectively;At 7 days after surgery,the mRNA of collagen-Ⅰ were 17.9±5.8,7.2±1.8 and 6.7±2.4,the mRNA of collagen-Ⅱ were 12.5±3.4,2.8±1.3 and 1.2±0.4 in SO,AGR and PGR group respectively.The SO group had significantly upregulation of collagen-Ⅰ and collagen-Ⅱ mRNA compared with the AGR and PGR groups at 3 days and 7 days respectively after surgery(P＜0.05).There was a significant difference of the collagen-Ⅱ between AGR group (2.8±1.3) and PGR group (1.2±0.4) at 7 days after injury(P＜ 0.05).The fracture bony callus in PGR group was a significantly larger and less ossified than that in the AGR group.The mechanical load of fracture in SO group was larger than that of the other 2 groups (P＜0.05).Conclusion Sensory denervation negatively affects fracture-healing.The ganglion of sensory nerve plays an important role in bone fracture healing and normal innervation is essential for the fracture repair.

A 2-month-and-20-day-old girl was hospitalized because of slow weight gain for 20 days.The patient was diagnosed as anemia,pneumonia and neutrophils firstly,and showed no improvement during anti-infective therapy,blood transfusion,and leukopenia drugs.The urinary organic acid spectrum of the patient showed increased methylmalonic acid slightly,but the normal value was found by 4 tests,which was inconsistent with the typical methylmalonic aciduria.By analyzing clinical manifestations and plasma homocysteine,folic acid and vitamin B12 levels,she was considered to have intracellular cobalamin metabolic disorder.Then,normal diet,intramuscular injection of vitamin B12,and feeding calcium,betaine,and L-carnitine were given,and the girl's symptoms were improved significantly.Latter gene analysis further showed that the patient had methylmalonic aciduria CblC type.Clinical manifestations of methylmalonic aciduria are complex and individually various,different therapies showed be applied to different causes.The value of urinary methylmalonic acid level alone cannot judge etiology;diagnosis should be based on blood amino acids and carnitine spectrum,homocysteine level and vitamin B12 level.

Objective To explore the role of human papillomavirus (HPV) in squamous cell carcinoma of the larynx.Methods A cohort of 152 laryngeal squamous cell carcinoma (LSCC) patients,40 premalignant lesions of the larynx,and 40 vocal fold polyp patients was evaluated for the expression of HPV16 E7 protein by immunohistochemistry (IHC).E7 protein expression was correlated with clinicopathological features and outcomes.Results The expression of E7 protein in vocal fold polyp was negative,and it's positive expression in precancerous lesions and laryngeaI carcinomas was 2.5％,and 32.9％,respectively.There were no other significant clinical or demographic differences between pl6-positive and-negative cases.There was no difference in overall survival (OS) between E7-positive and-negative patients with 5-year survival of 79％ and 66％ for p16 positive and negative patients,respectively (P =0.581).There was no statistically significant difference in failure-free survival (FFS) with 5-year FFS of 57.8％ and 42.3％ for p16 positive and negative patients,respectively (P =0.579).Conclusions E7 expression is infrequent in laryngeal carcinomas.There are no statistically significant correlations between E7 IHC status and OS or FFS.