The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective:To investigate the types, incidences, and clinical characteristics of shock in polytrauma patients at different stages after polytrauma.Methods:A retrospective study was conducted on polytrauma patients admitted to multiple trauma centers from June 2020 to December 2021. The inclusion criteria were patients >18 years old and treated due to polytrauma. Exclusion criteria included an admission time of more than 48 h after trauma, a history of malignancy, or metabolic, consumptive, and immunological diseases. The early stage was defined as the period of ≤48 h after polytrauma, and the middle stage was defined as the period between 48 h and 14 days. The patient’s medical history, clinical manifestations, laboratory tests, imaging examination, injury severity score (ISS), and Glasgow coma scale (GCS) were collected. The types, incidences, and clinical characteristics of shock in different stages after polytrauma were analyzed, according to the diagnostic criteria of each type of shock. The differences between the groups were compared by Student’s t test, χ2 test or Mann-Whitney U test. Results:The incidence of the early and middle stage shock after polytrauma were 73.1% and 36.4%, respectively, with statistically significant difference between stages ( P<0.01). There were significant differences in the incidence of hypovolemic shock (83.6% vs. 28.4%), distributed shock (13.7% vs. 80.9%) and cardiogenic shock (3.5% vs. 6.6%) between stages (all P<0.05). The incidence of obstructive shock (8.4% vs. 9.7%, P>0.05) was similar between stages. The incidence of undifferentiated shock was 1.6% and 1.2%, respectively. There were 9.5% patients with multifactorial shock in the early stage and 14.4% in the middle stage. Totally 7 combinations of multifactorial shock were found in different stages after polytrauma. In the early stage, the combination of HS and DS accounted the highest ratio (42.3%) and followed by HS and OS for 28.8%. In the middle stage, the combination of HS and DS was the most common (48.6%) and followed by DS and OS (24.3%). Conclusions:The incidence of shock in polytrauma patients is high. Different types of shock can occur simultaneously or sequentially. Therefore a comprehensive resuscitation strategy is significant to improve the success rate of treatment.

Objective To analyze and assess the postoperative motor function in children with spastic cerebral palsy (SCP) by surface electromyography (sEMG) and joint angle. Methods Sixteen children with SCP were involved in this study. The sEMG of rectus femoris, biceps femoris, semitendinosus, tibialis anterior, lateral gastrocnemius and medial gastrocnemius muscles and joint angles of the hip, knee and ankle during straight walking were collected preoperatively and postoperatively. In every gait phase, the mean values of joint angles, root mean square and integrated electromyography of sEMG were calculated, to evaluate muscle strength and muscular tension quantitatively. Results The muscle tension of lower limbs was significantly decreased (P<0.05). The muscle strength of rectus femoris and biceps femoris was decreased in the swing phase. At the midswing and terminal swing phase, the strength of tibialis anterior increased significantly (P<0.05). The flexion angle of hip and knee decreased significantly (P<0.05). The dorsiflexion angle of ankle increased significantly (P<0.05), and the varus angle decreased significantly (P<0.05). Conclusions After operation, the crouching gait and clubfoot were improved positively. Therefore, the motor function of children was improved. Combining sEMG and joint angle can evaluate the muscle function of patients quantitatively, and it also can provide references for clinical diagnosis.

【Objective】 To compare the ability of body mass index （BMI）， body fat percentage （BFP）， waist circumference （WC）， waist-to-height ratio （WHtR）， visceral fat index （VFI） and the combinations of two kinds of obesity indices to predict the risk of hypertension. 【Methods】 Data collected in the baseline survey of “Gansu Province’s Urban and Rural Natural Population Cohort Establishment and Tumor Follow-up Study” were analyzed. Area under the curve （AUC） of ROC curve with covariates was used to analyze and compare the effects of individual obesity evaluation index and the combination of two kinds of obesity indices in predicting the risk of hypertension. 【Results】 Analyses of data of 20，079 adults showed that the AUC of BMI， WC， WHtR， BFP and VFI was 0.636， 0.604， 0.615， 0.614 and 0.619， respectively. AUC of the combination of BMI and WC （0.643） was higher than that of BMI （0.636）； however， the change rate of AUC was only 1.09%. AUC of the combinations of WC， WHtR and VFI， the three central obesity evaluation indices， and BFP， a general obesity evaluation index， were lower than that of BMI. The optimal cutoff value for BMI was 24.2 kg/m². 【Conclusion】 The effect of BMI in predicting the risk of hypertension is better than that of BFP， WC， WHtR and VFI. The effects of the combinations of the two kinds of obesity evaluation indices are not better than that of BMI. To prevent and control hypertension， adults should keep their BMI under overweight.

Objective:Standardized sample resources and high-quality clinical big data are important resources for medical research, only through resource sharing can maximize its utilization.Which can be utilized to the max only through resource sharing.Methods:This paper attempts to explore the sharing mechanism of the resource sharing platform and proposes some aspects such as the platform construction background, management regulations, legal ethical system, data sharing principles, benefit distribution, etc.This article attempts to explore the sharing mechanism based on the resource sharing platform of the respiratory disease biobank, proposes the contents that should be included in the sharing mode.Detailed information including the platform construction background, management procedures, legal and ethical system, data sharing principles and benefit distribution should take into consideration in the operating mechanism of the platform.Results:Establishing a resource sharing platform matches the development of clinical research in China.The tailored sharing model which is suitable for the field of respiratory diseases will also guide the rapid development of clinical research.Conclusions:The construction of a respiratory disease biobank sharing platform is conducive to promoting the opening and sharing of biological samples and information resources in the context of big data.

Objective To investigate the prevalence and endoscopic detection rate of proximal serrated polyps and to screen the risk factors. Methods The data of 9010 colonoscopies performed by 22 endoscopists between September 2016 and September 2017 were reviewed. The adenoma detection rate (ADR) and proximal serrated polyp detection rate (PSDR) were calculated, and the correlation between ADR and PSDR was estimated by Pearson correlation coefficients. Multivariate logistic regression was used to analyze PSDR among endoscopists. Results For all subjects, the mean ADR was 30. 07％ ( ranged from 20. 00％ to 40. 78％) and mean PSDR was 4. 70％ ( ranged from 1. 52％ to 9. 28％) . PSDR of males was 1. 38 times of that of females ( OR=1. 38, 95％CI:1. 13-1. 69, P<0. 01) . For 3560 cases ( 39. 51％) of 50 years and older subjects, the mean ADR was 45. 01％ ( 28. 99％-57. 78％) and mean PSDR was 6. 08％(2. 07％-10. 56％). PSDR was moderately correlated with ADR (r=0. 48, P=0. 02). PSDR of males was 1. 36 times of that of females (OR=1. 36, 95％CI: 1. 04-1. 80, P=0. 03). Endoscopist was a significant risk factor for detection of proximal serrated polyps ( P<0. 01) . Compared with endoscopist with the highest PSDR, odds ratio of other endoscopists ranged from 0. 16 (95％CI:0. 06-0. 40, P<0. 01) to 0. 83 (95％CI:0. 53-1. 32, P=0. 44) . Conclusion Proximal serrated polyps are more common in males, who are over 50 years old. The PSDR is highly variable and dependent on endoscopists. It is possible that a certain proportion of proximal serrated polyps are missed during colonoscopy.

Objective: To investigate the anatomical features of the safe zone for sacral lateral mass screw placement and find the safe trajectory, so as to provide reference for clinical application. Methods: The three-dimensional computed tomography scan materials of sacrococcygeal vertebrae in 60 patients admitted to the Liaocheng People's Hospital of Shandong Province were analyzed by Mimics software to establish three-dimensional models. There were 33 males and 27 females, aged 25-78 years, with an average age of 45.7 years. After the safe zone was separated from sacral lateral mass model, a maximum cylinder was placed into the safe zone according to its anatomical feature. The cylinder was established as safe trajectory. Anatomical data were measured, including the length and diameter of screw trajectory, the distance between the entry point and the middle jaw, and adjacent upper and lower foramen, as well as the intersection angle between the screw direction and sagittal plane, between the screw direction and the adjacent upper end plate. Results: The restriction factor of screw size on S₁, S₂ lateral mass was transverse diameter, while the restriction factor on S₃, S₄ was the distance between adjacent intervertebral foramen. The maximal length of screw from S₁ to S₄ was 30 mm, 35 mm, 30 mm, 14 mm respectively, while the maximal diameter was 12 mm, 9 mm, 5 mm, 5 mm respectively. The best entry point of S₁ mass screw was lateral to the zygopophysis. The best entry point of S₂-S₄ mass screw was located at the midpoint of a line connecting the lateral edge of adjacent posterior sacral foramen approximately about 2 cm from median sacral crest. The leaning angles of screw was increased successively, and the sagittal plane was slightly inclined. There were significant differences between male and female groups in the leaning angle in S₂ [male: (35.8±1.2)°, female: (37.9±3.7)°] and the distance between entry point and median sacral crest [male: (20.5±1.0)mm, female: (19.1±1.4)mm](P<0.05), while there was no significant difference in other parameters (P>0.05). Conclusions Cylindrical bony channel which is feasible for screw placement can be found in the lateral mass of sacrum. Individualized measurement can provide reference for application of lateral mass screw.

[Objective]To observe the dynamic changes of serum LH levels in different GnRH-along protocols ,and investigate the relationship between GnRH-adosage and LH levels ,and compare the clinical outcomes among different GnRH-a long protocols.[Methods]In this retrospective study,1.0 mg,0.8 mg,0.375 mg long-acting and 0.1 mg/d,0.05 mg/d short-acting GnRH-a long protocols were included from January to June in 2015 at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-Sen University. Serum LH levels were evaluated from a total of 250 women at the four time points,on the day before gonadotropin stimulation(Gn0),the fourth day of Gn stimulation(Gn4),the seventh day of Gn stimulation(Gn7),and the HCG administration day(HCG day),then the relationship between serum LH levels and the dosage of GnRH-a were analyzed. The number of oocytes retrieved,fertilization rate,good quality embryos rate,blastocyst transferred rate,the number of transferred embryos,implantation rate and clinical pregnancy rate were also compared.[Results]Among the long-acting groups,LH levels in 0.375 mg group were higher than those in 1.0 mg and 0.8 mg groups at the four time points(P<0.05). Total Gn dose,duration of Gnstimualtion and HMG dosage of 1.0 mg protocol and 0.8 mg protocol were significantly higher than those of 0.375 mg group(P < 0.05). In addition,the implantation rate showed an increasing tendency when the level of LH increases(P>0.05). In short-acting groups,the LH levels in 0.05 mg/d protocol were significantly lower than those in the 0.1 mg/d group at Gn0,Gn7 and HCG day(P<0.05). Total Gn dose,du?ration of Gn stimulation and HMG dosage did not show significant difference between 0.05mg and 0.1mg group. What′s more,the im?plantation rate in 0.1 mg/d group was higher than in 0.05 mg/d group(P>0.05).[Conclusion]Among the long-acting groups,the smaller amount of GnRH-a was administrated ,the higher LH levels during ovarian stimulation and implantation rate the patients ob?tained. As to the short-acting groups,the LH level and implantation rate in 0.1 mg/d group is higher than those in 0.05 mg/d group.

Purpose To observe the shape of postnatal early female pelvic diaphragmatic hiatus and the mobility of lower urinary tract bladder neck with three-dimensional transperineal ultrasound,and to analyze the related parameters of postnatal early stress urinary incontinence (SUI) to screen SUI early after delivery and provide objective indices for pelvic floor rehabilitation.Materials and Methods 170 primiparae,including 13 cases of SUI group and 157 cases of asymptomatic group,were operated pelvic floor ultrasonic examination,human pelvic floor midsagittal sections and pelvic diaphragmatic hiatus rebuilding images were obtained,and such related biological parameters as bladder neck mobility and pelvic diaphragmatic hiatus indicators were determined.Results The incidence of SUI at 6-8 weeks after delivery was 4.55％,and that after vaginal delivery was 9.61％,the difference was not statistically significant (P＞0.05).The lower migration of the bladder neck (1.83±0.54) cm on Valsalva maneuver,and transverse diameter (421±0.73) cm,vertical diameter (5.89±0.97) cm and area (20.38±6.30) cm2 of pelvic diaphragmatic hiatus in SUI group were greater than those in the asymptomatic group (P＜0.05),and the difference between parameters of the two groups in resting state and anal shrinkage was of no statistical significance (P＞0.05).Conclusion The shape of urethra,lower migration of bladder neck and the parameters of pelvic diaphragmatic hiatus on Valsalva maneuver are sensitive indicators in ultrasonic evaluation of SUI,are conductive to screening of SUI after early delivery in combination with patient symptoms and can guide the high risk puerpera for early pelvic floor rehabilitation.

This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was
12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .