ObjectiveTo explore the effects of Bushen Tiaojing Formula （补肾调经方） on the quality of early embryos in repeated controlled ovarian stimulation （COS） and its possible mechanism. MethodsA total of 150 ICR female mice were divided into a normal group， a model group， an inhibitor group， a low-dose and a high-dose Bushen Tiaojing Formula group. Mice in the normal group， inhibitor group and model group were gavaged with distilled water 0.25 ml a day， and mice in the low- and high-dose groups were given 25.6 and 51.2 g/（kg·d） of Bushen Tiaojing Formula， respectively. All groups were gavaged once a day for 13 days as a cycle. Mice in the normal group were injected intraperitoneally with 0.1 ml normal saline on the 11th day of gavage， while mice in the other four groups were used to establish COS models. The inhibitor group was injected with the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid 0.2 ml one hour before modelling. All groups were injected by gavage and intraperitoneal injection for 3 consecutive cycles， with an interval of 4 days between cycles. Immediately after the third intraperitoneal injection， mice were grouped with male mice of the same strain in a ratio of 2∶1， and at 8AM of the second day， the mice were examined， and those with spermatozoa or spermatozoa in the vaginal smears were recorded as pregnant. The mice were executed in the afternoon of the 4th day of pregnancy， and the blastocysts were obtained under an inverted microscope. The morphology of the blastocysts was observed， and the total number of blastocysts and the number of high-quality blastocysts were recorded to calculate the rate of high-quality blastocysts； the apoptosis of blastocyst cells was detected by the Tunel method， and the apoptosis rate was calculated； the endoplasmic reticulum molecular chaperone protein glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， B-lymphoblastoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cystathionin 3 （Caspase-3） and cystathionin 12 （Caspase-12） protein levels and their mRNA expression were detected by immunofluorescent assay and RT-qPCR assay， respectively. ResultsIn the normal group， blastocysts had regular morphology， good morphological development and low fragmentation rate； in the model group， blastocysts were poorly developed， cell morphology was irregular， fragmentation rate was high， and there was some stagnation； in the inhibitor group and high-dose， low-dose Bushen Tiaojing Formula groups， cell morphology could be seen to be better developed， with regular morphology and less fragmentation rate. Compared with the normal group， the rate of high-quality blastocysts in the model group reduced， the rate of apoptosis of blastocyst cells increased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and its mRNA expression in blastocysts increased， while the level of Bcl-2 protein and its mRNA reduced （P＜0.01）. Compared with the model group， the rate of high-quality blastocysts increased， the rate of apoptosis of blastocysts decreased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and their mRNA expression decreased， and the levels of Bcl-2 protein and its mRNA expression increased in the blastocysts in the inhibitor group and the high-dose and low-dose Bushen Tiaojing Formula groups （P＜0.01）. Compared with the inhibitor group， GRP78， CHOP， Caspase-12， Bax protein levels and their mRNA expressions increased in the high-dose Bushen Tiaojing Formula group， and Caspase-12， Caspase-3， Bax protein levels and their mRNA expressions increased in the low-dose formula group （P＜0.05 or P＜0.01）. ConclusionBushen Tiaojing Formula can inhibit the apoptosis of blastocyst cells caused by repeated controlled ovarian stimulation by improving endoplasmic reticulum stress， which plays a role in improving the quality of early embryos.

Objective:To explore the clinical effects of free anterolateral thigh perforator flap (ALTPF) with modified cross-leg vessel bridging in reconstruction of infected wounds in the lower leg combined with major vessel defects.Methods:A retrospective observational study was conducted on 7 patients who admitted to the Department of Trauma Orthopaedics, the 521 Hospital of Norinco Group from January 2020 to December 2021 for treatment of large infected wounds in lower leg with soft tissue defect by reconstructive surgery of flap transfer. The patients were 5 males and 2 females, aged 23-50 years old with an average age of 37 years old. The causes of injury were: 5 patients were of car accidents, 1 of machinery compression and 1 of heavy object crush. The wounds were reconstructed after debridement and infection control with sensitive antibiotics, where the soft tissue defects were found at 11.0 cm×15.0 cm to 20.0 cm×32.0 cm in size. All patients underwent vascular angiography or CDU examinations and it was confirmed that the affected calf had only an anterior tibial artery as the vessel left for blood supply in 6 patients and a posterior tibial artery as the blood supply vessel in one patient. Therefore application of vascular end-to-side anastomosis in free flap reconstruction of limb defects was impossible due to the damaged artery could not be salvaged as a blood supply artery for the transferred flap. Therefore, a modified cross-leg vessel bridging to the freed ALTPF in the affected lower leg was applied. The donor site of the pedicle was covered with VSD while the pedicle of the flap was anastomosed. It was remained until the posterior tibial artery and the tubular flap were ready for replantation after disconnection of the pedicle. The sizes of flap were 13.0 cm×17.0 cm to 22.0 cm×32.0 cm (unilateral ALTPFs for 6 patients and bilateral ALTPFs for 1 patient). Two donor sites in low tension were direct closed, and the rest of 5 donor sites that had great tensions and could not be directly sutured were reconstructed by skin grafting. The survival and complications of flaps were observed in the scheduled postoperative follow-ups at outpatient visits, WeChat reviews and home visits, etc.Results:All 7 patients were successfully treated and had 12-24 months postoperative follow-up, with an average of 16 months. All flaps survived, with primary healing in 6 patients and 1 patient had partial flap necrosis with surface infection, which healed after dressing changes. The wound healing time was 14-36 days with an average of 17.9 days. The time for disconnection of the cross-leg vessel bridging pedicle was 3-4 weeks with the flap transfer, with an average of 3.6 weeks. The donor sites of ALTPFs and vessel pedicles all healed well. CDU confirmed the patency of the contralateral posterior tibial artery. Satisfactory functional recovery was achieved in the affected lower limb and there was a good function of the contralateral healthy lower leg.Conclusion:Application of the transfer of a free ALTPF with modified cross-leg vessel bridging in reconstruction of infected wounds with major vessel defects in the lower leg has shown excellent clinical outcomes. It is a practical and effective method in treatment of large infective defect in lower leg.

Objective To explore the influencing factors of visual acuity recovery in patients with high myopia after posterior chamber phakic intraocular lens(ICL)implantation.Methods A prospective study was conducted on 210 pa-tients(420 eyes)with high myopia who underwent ICL implantation at the Second Affiliated Hospital of Zhengzhou Univer-sity from May 2021 to March 2023.The patients were divided into a good recovery group[best corrected visual acuity(BC-VA)recovery ≥0.3 D]and a poor recovery group(BCVA recovery＜0.3 D)based on their visual acuity recovery status three months after surgery.The baseline data of patients in the two groups were compared,and the factors affecting visual acuity recovery were analyzed using Logistic regression.The receiver operating characteristic(ROC)curve was used to an-alyze the predictive value of the Logistic regression model for poor visual acuity recovery in patients with high myopia after ICL implantation.Results Three months after surgery,149 patients(298 eyes)were in the good recovery group,and 61 patients(122 eyes)were in the poor recovery group.There were no significant differences in gender,age,years of myopi-a,body mass index,and academic performance between the two groups(all P＞0.05).The proportions of patients with corneal astigmatism＜1.30 D(55.74％),corneal diopter＜45 D(59.02％),Pittsburgh Sleep Quality Index(PSQI)＜7 points(63.93％),and average central radius of curvature[(7.82±0.27)mm]in the poor recovery group were lower than those in the good recovery group[83.89％,81.88％,85.91％,and(7.90±0.24)mm,respectively].The central flat me-ridian curvature(k1)of the anterior corneal surface[(43.27±1.43)D],steep meridian curvature(k2)of the anterior corneal surface[(44.84±1.53)D],and arch height[(628.49±67.28)μm]in the poor recovery group were higher than those in the good recovery group[(42.73±1.42)D,(44.12±1.47)D],and[(417.56±80.14)pm],with significant differences(all P＜0.05).Logistic regression analysis showed that corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score were independent influencing factors of poor visual acuity recovery after ICL implantation in pa-tients with high myopia(all P＜0.05).ROC curve analysis showed that the area under the ROC curve for predicting poor visual acuity recovery after ICL implantation in patients with high myopia by Logistic regression model was 0.938(95％CI:0.896-0.966),the sensitivity was 83.61％,and the specificity was 91.95％(P＜0.05).Conclusion The visual acuity recovery after ICL implantation in patients with high myopia is affected by corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score.The Logistic regression model based on these factors has high predictive value for visual acui-ty recovery after ICL implantation.

Objective To build a whole-course nursing quality evaluation system for liver transplanta-tion in children,so as to provide a basis for nursing quality evaluation and management.Methods With Donabedian's"structure-process-outcome"model as the theoretical framework,we employed literature analysis,Delphi method,and hierarchical analysis to determine the contents and weights of indexes in the whole-course nursing quality evaluation system for liver transplantation in children.Results The three rounds of survey based on questionnaires showed the questionnaire recovery rate of 100% ,the expert authority coefficients of 0.95,0.96,and 0.98,and the Kendall's coefficients of concordance of 0.165,0.209,and 0.220,respectively(all P<0.001).The established nursing quality evaluation system included 3 first-level indexes,15 second-level inde-xes,and 67 third-level indexes.Conclusion The whole-course nursing quality evaluation system for liver trans-plantation in children that was built in this study can provide a basis for the evaluation of the nursing quality.

OBJECTIVE To synthesize a polymer PEI-ss-PEG2000-DSPE containing disulfide bond and to prepare as cationic micelle(P-ss-PD) based on branched polyethyleneimine(PEI). To investigate the ability of P-ss-PD micelle to reduce cytotoxicity and improve the transfection efficiency of antisense oligonucleotide(ASO) in human breast cancer cell lines, and to study the anti-tumor effect of P-ss-PD micelle in nude mice. METHODS PEI-ss-PEG2000-DSPE was synthesized by grafting PEG2000-DSPE onto branched PEI with disulfide bond as a connecting arm. P-ss-PD micelle was prepared by ethanol injection method and P-ss-PD/ASO nanocomplex was obtained by combining P-ss-PD micelle with ASO. The particle size and zeta potential of P-ss-PD/ASO nanocomplex at various mass ratios were determined by laser particle size analyzer. Agarose gel retardation assay was used to investigate the binding degree of P-ss-PD/ASO nanocomplex and determine the optimal mass ratio. At the same time, the reduction responsive ability of P-ss-PD micelle was investigated. The cytotoxicity of P-ss-PD micelle was detected by CCK8 kit. The transfection efficiency of P-ss-PD micelle was investigated by flow cytometry and high content cell imaging analysis system in MDA-MB-231 cells. The anti-tumor effect of P-ss-PD micelle was investigated by tumor-bearing nude mice models. RESULTS When the mass ratio was 300∶1, the particle size of P-ss-PD/ASO nanocomplex was the smallest and had a good stability. The average particle size was (58.90 ± 4.08)nm, the average zeta potential was (16.80 ± 1.23)mV, and the morphology was uniform spherical. P-ss-PD/ASO nanocomplex had the reduction responsive ability and could release ASO under highly reductive conditions.In vitro, compared with unmodified branched PEI, the cytotoxicity of P-ss-PD micelle was significantly reduced and the transfection efficiency was significantly increased.In vivo, the tumor growth inhibition rate of P-ss-PD/ASO nanocomplex in tumor-bearing nude mice was more than 50%. CONCLUSION The P-ss-PD micelle prepared in this study is a kind of low toxicity and high transfection efficiency non-viral vector, which has the characteristics of reduction responsive releasing, and shows a promising application in ASO drug delivery.

Objective To explore the correlation between moderate to severe bronchopulmonary dysplasia (BPD) and early breastfeeding in preterm infants with a gestational age of ≤32 weeks. Methods A retrospective analysis was conducted on the clinical data of 220 preterm infants with a gestational age of ≤32 weeks. The preterm infants were dividedinto moderate to severe BPD group (37 cases) and control group (183 cases) based on whether moderate to severe BPD occurred or not. The clinical characteristics, breastfeeding volume, and mother's own milk (MOM) feeding rate were compared between the two groups, and the relationship between breastfeeding and the occurrence of moderate to severe BPD in preterm infants was analyzed. Results Univariate analysis showed that the moderate to severe BPD group had a higher proportion of infants with birth weight < 1 500 g, gestational age < 28 weeks, vaginal delivery, Apgar score ≤ 7 at 1 minute after birth, and mechanical ventilation time ≥ 7 days compared to the control group(P < 0.05). The duration of intravenous nutrition was longer in the moderate to severe BPD group (P < 0.05). The moderate to severe BPD group had lower breast milk intake from 0 to 7 days after birth, MOM intake, MOM feeding rate, and breast milk intake from 8 to 14 days after birth compared to the control group (P < 0.05). Multivariate Logistic regression analysis showed that a high volume of breastfeeding from 0 to 7 days after birth was an independent protective factor for the occurrence of moderate to severe BPD in preterm infants (OR=0.865, 95%CI, 0.767 to 0.976, P < 0.05). Gestational age < 28 weeks (OR=5.238, 95%CI, 1.158 to 23.686, P < 0.05), and mechanical ventilation time ≥7 days (OR=22.386, 95%CI, 6.769 to 74.030, P < 0.05) were independent risk factors for the occurrence of moderate to severe BPD in preterm infants. Conclusion Early breastfeeding after birth can significantly reduce the risk of moderate to severe BPD in preterm infants with a gestational age of ≤32 weeks, and clinical measures should be actively implemented to promote early breastfeeding.

Objective　To analyze the identification of pathogenic bacteria in municipal sewage of Hangzhou City, Zhejiang Province from January to October 2023, to understand the serotype and drug resistance of Vibrio cholerae isolated from sewage, as well as to predict the virulence gene and drug resistance gene carrying situation. Methods From January to October 2023, urban sewage samples from various environments in Hangzhou City, Zhejiang Province, were continuously collected for bacterial isolation and culture. The serotypes of 27 Vibrio cholerae strains were identified by slide agglutination method, and the drug sensitivity test was conducted by micro broth dilution method. Whole genome sequence and bioinformatics software were used to predict drug resistance genes and virulence genes. Results The sewage identification results showed 26 bacteria genera, including Salmonella, Vibrio, Enterobacter, and Aeromonas, among 82 bacterial species. All 27 strains of Vibrio cholerae were non-O1 and non-O139 serogroups. The strains showed high resistance rates to ampicillin, ampicillin/sulbactam and cotrimoxazole at 59.26%, 14.81%, and 14.81%, respectively), exhibited high sensitivity to cefotaxime, tetracycline, chloramphenicol, meropenem, ertapenem, ceftazidime, ceftazidime/avibactam, amikacin, ciprofloxacin, tigecycline, and azithromycin. A total of 21 different drug resistance genes were detected in 11 strains of Vibrio cholerae, among which the highest carriage rate of β-lactam resistance genes reached 63.64%, and 1 strain carried 17 kinds of drug resistance genes. None of the 11 strains of Vibrio cholerae carried ctxA, ctxB, ace, zot, or chxA genes, but all the strains carried rtxB, rtxC, and rtxD genes; 90.91% of the strains carried hlyA, and 36.36% carried rtxA. Conclusions All Vibrio cholerae isolated from sewage in this study are non-O1 and non-O139 serogroups, showing good sensitivity to most antibiotics, but also they carry a certain number of drug-resistance genes and virulence genes. This suggests that future monitoring efforts should focus on these strains, providing certain data support for the study of the characteristics of Vibrio cholerae isolated from sewage.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Objective To analyze the influencing factors of mechanical phlebitis(MP)during peripherally inserted central catheterization(PICC)in very/extremely low birth weight infants(VLBWI/ELBWI)in neonatal Intensive Care Unit(NICU).Methods The clinical data of VLBWI/ELBWI who underwent PICC catheterization were retrospectively analyzed.Multivariate Logistic regression model was used to analyze the influencing factors of MP.Results The incidence of MP after implementa-tion of PICC in VLBWI/ELBWI was 26.1％(116/444).Univariate analysis showed that the position of catheter tip,catheter vein,gestational age,body mass at birth,gestational age when cathetering,body mass when cathetering,puncture times and length were influencing factors for MP in VLBWI/ELBWI(P＜0.05).Multivariate Logistic regression analysis showed that abnormal position ofcathe-ter tip(OR=2.526;95％CI,1.532 to 4.164)and puncture times ≥ 2 times(OR=1.952;95％CI,1.017 to 3.747)were independent risk factors.Conclusion The abnormal catheter tip position and the number of puncturing ≥2 times increase the risk of mechanical phlebitis in VLBWI/ELBWI after PICC.Early intervention should be taken as soon as possible to avoid the occurrence of MP so as to relieve infants'pain and improve the quality of clinical care.

OBJECTIVE: To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese. METHODS: Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells. RESULTS: Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC₅₀) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L. CONCLUSION This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.