OBJECTIVE To explore the efficacy and safety of different doses of bupivacaine liposome （referred to as “LB”） in posterior quadratus lumborum block （QLB） for postoperative analgesia in patients undergoing cesarean section （CS）. METHODS In prospective research method， a total of 168 patients undergoing CS admitted to Chongzhou Maternal and Child Health Hospital from June to December 2024 were randomly divided into LB1 group， LB2 group， and LB3 group （LB of 199， 133 and 67 mg， respectively） according to the random number sorting method， with 56 cases in each group. All patients underwent CS after combined spinal-epidural anesthesia， and received patient-controlled intravenous analgesia and bilateral posterior QLB with different doses of LB after the operation. Visual analogue scale score， Ramsay sedation score， the presence of postoperative block planes and muscle strength classification were observed in the three groups of patients at 6， 12， 24， 48 and 72 hours after the operation. The time of the first compression of the analgesic pump， the dosage of sufentanil and butorphanol within 72 hours after surgery， the number of compressions of the analgesic pump， the analgesic rescue rate， the time of initiating lactation， the score of neonatal behavioral neurological assessment （NBNA）， the time of postoperative exhaust， the indwelling time of urinary catheter， the length of hospital stay， and the total satisfaction at 72 hours after surgery were compared. The occurrence of adverse reactions within 72 hours after the operation was recorded. RESULTS The resting and motor pain scores， the dosage of sufentanil and butorphanol within 72 hours after surgery， the number of compressions of the analgesic pump， the analgesic rescue rate， and the time of initiating lactation at 6， 12， 24， 48 and 72 hours after surgery in the LB1 group and the LB2 group were significantly lower or shorter than those in the LB3 group（P＜0.05）. The proportion of postoperative block planes at 24， 48 and 72 hours after surgery， the time of the first compression of the analgesic pump and the total satisfaction in the LB1 group and the LB2 group were significantly higher or longer than those in the LB3 group（P＜0.05）. The proportion of patients with muscle strength≤grade 3 at 6 hours after surgery in the LB1 group was significantly higher than that in the LB2 and the LB3 groups （P＜0.05）. There were no statistically significant differences in the Ramsay sedation scores at each time point after surgery， NBNA scores， postoperative exhaust time， urinary catheter indwelling time， the length of hospital stay， as well as the occurrence of adverse reactions among the 3 groups （P＞0.05）. CONCLUSIONS Compared with 67 mg of LB， 199 mg and 133 mg of LB can improve the postoperative analgesic effect and total satisfaction of CS patients undergoing posterior QLB， reduce the use of postoperative analgesic drugs， and shorten the time to start lactation. Compared with 199 mg and 133 mg of LB， 67 mg of LB has a smaller impact on the motor function of CS patients. All three doses of LB had no significant effect on the neurobehavioral abilities of newborns, and demonstrated comparable sedative efficacy and safety.

Abstract: To date, the investigation of the functional composition of Centella asiatica (L.) Urban has been mainly focused on the triterpenoid saponins, with little research on the other compositions. The acetic acid-induced writhing, Eddy's hot plate and formalin tests were employed to investigate the anti-nociceptive effects of madecassic acid (MA). The experiment was divided into normal control group, acetylsalicylic acid (ASA) group, and the MA groups of low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) dosage. Meanwhile, the anti-nociceptive effect of MA on the acetic acid and formalin-induced nociceptive models in the absence and presence of NAL (naloxone hydrochloride) was evaluated. To have an insight into the anti-nociceptive mechanisms of MA, the capsaicin- and glutamate-induced paw licking tests were also employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results showed that MA exhibited good anti-nociceptive activity in the acetic acid-induced writhing test and the second phase of formalin test; the anti-nociceptive effect of MA in both the acetic acid and formalin-induced nociception was not effectively removed by NAL; MA (20 mg/kg and 40 mg/kg) effectively reduced the duration of biting/licking the capsaicin-injected paw with inhibition rates of 29.5% and 64.4%, respectively; MA (20 mg/kg and 40 mg/kg) distinctly shortened the time spent in biting/licking the glutamate-injected paw by 30.9% and 56.1%, respectively. In summary, MA induces significant peripheral anti-nociceptive effect, and the anti-nociceptive activities probably involve the modulation of glutamatergic systems and vanilloid systems (TRPV1) instead of the opioidergic system.

Objective To explore the dynamic changes in cerebral hemodynamics in patients with unilateral middle cerebral artery(MCA)occlusion after superficial temporal artery(STA)-MCA bypass surgery.Methods One hundred and nine patients diagnosed with unilateral MCA occlusion by DSA who underwent STA-MCA bypass surgery were retrospectively included in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University.Clinical data of patients were collected within 24 hours after admission,including age,sex,body mass index,stroke risk factors including hypertension,hyperlipidemia,diabetes,smoking,drinking history and atrial fibrillation,clinical manifestations(within the last 6 months;nonspecific symptoms[dizziness,memory loss,unresponsiveness,etc.],transient ischemic attack,and stroke),blood biochemical markers(low density lipoprotein cholesterol,high density lipoprotein cholesterol,triglyceride,total cholesterol,fasting blood glucose,and hypersensitive C-reactive protein),and National Institutes of Health stroke scale(NIHSS)score at admission.Color Doppler ultrasound(CDU)and transcranial color coded Doppler(TCCD)ultrasound were used to evaluate the hemodynamic parameters of STA before and at different periods after surgery(4-7 days and 1,3,6,12 months after surgery)to analyze the patency of bypass arteries and intracranial hemodynamic changes,and to check the consistency of the results of the bridge artery patency at 12 months postoperatively by CDU and DSA,consistency test was performed.According to the results of the DSA examination 12months after surgery,the patients were divided into the bypass artery patency group and the non-patency group(stenosis or occlusion).The hemodynamic parameters at the trunk of STA,namely the extracranial segment,transcranial,and intracranial part of the bypass arteries,were compared between the two groups.It included inner diameter(D),peak systolic velocity(PSV),end-diastolic velocity(EDV),resistance index(RI),pulsation index(PI),time-averaged mean velocity(TAMV),time-averaged peak velocity(TAPV),and calculated flow of the STA trunk including TAMV flow and TAPV flow.Head CT,CT angiography(CTA)above the aortic arch,and CT perfusion(CTP)of the whole brain were performed 1 to 3 days before surgery and 12 and 18 months after surgery to observe the changes in cerebral perfusion.Head CT was performed 1 to 2 days after the operation to observe whether there were new hemorrhagic and ischemic lesions in the operative area.the CTP parameters of the two groups were compared including 12 and 18 months after the operation with 1 to 3 days before the surgery,and the differences in CTP parameters between the two groups were compared.The modified Rankin scale(mRS)was used to evaluate the neurological function prognosis of the patients at 12 and 18 months after surgery.The mRS score 2 was divided into a good prognosis and mRS score≥3 was a poor prognosis.NIHSS score of the patients was recorded 7 days,12,and 18 months after surgery.Results(1)Consistency analysis of CDU and DSA:the consistency of the assessment of bypass artery patency was excellent at 12 months after surgery,and the Kappa value was 0.94(95％CI 0.81-1.00,P＜0.01).According to DSA,101 cases(92.7％)were in bypass artery patency group,while 8 cases(7.3％)in the non-patency group(no case of occluded bridge vessel was found),and the sites of stenosis in the bypass arteries were all located in the transcranial segment.(2)Hemodynamic parameters:compared with the preoperative results,the D of the extracranial segment increased on 4-7 days and 1,3,6,and 12 months after the operation(Wald x2=30.438).Hemodynamic parameters included increased blood velocity such as PSV,EDV,TAMV,and TAPV(Waldx2 was 12.117,29.310,31.075 and 17.525,respectively)and blood flow including TAMV flow and TAPV flow(Wald x2 was 54.503 and 34.986,respectively)increased,while RI and PI values were decreased(Waldx2 was 112.568 and 103.629,respectively),and the differences were statistically significant(all P＜0.05).However,there was no significant difference in hemodynamic parameters in the non-patency group at 12 months after operation(all P＞0.05).Compared with 4-7 days after surgery,PSV(252.0[206.8,315.3]cm/s vs.102.5[84.0,119.0]cm/s)and EDV(119.5[106.3,159.8]cm/s vs.43.5[36.8,52.0]cm/s)in the non-patency group were significantly higher at the cranial entrance 12 months after surgery(both P＜0.05),but there was no significant difference in RI and PI values(both P＞0.05).Compared with 4-7 days after surgery,the blood flow parameters of STA intracranial segment,including PSV(29.4[24.8,41.4]cm/s vs.111.5[63.3,120.0]cm/s),EDV(19.7[15.2,22.2]cm/s vs.58.5[28.3,70.0]cm/s)and PI(0.55[0.42,0.63]vs.0.83[0.61,0.90])values in the non-patency group at 12 months after surgery were significantly decreased(all P＜0.05).(3)CTP parameters:the relative cerebral blood flow(rCBF)of the patency group increased at 12 and 18 months after surgery compared to preoperative levels,while relative cerebral blood volume(rCBV),relative peak time(rTTP)and relative mean transit time(rMTT)decreased,with statistical significance(all P＜0.05).At 12 and 18 months after operation,rCBF increased,while rMTT decreased in the non-patency group(both P＜0.05),but there was no significant difference as for rCBV and rTTP.The rTTP of the patency group at 12 and 1 8 months was lower than that of the non-patency group(12 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.024;1 8 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.023),but there was no statistical significance for other parameters between the two groups(all P＞0.05).(4)NIHSS score and prognosis:clinical follow-up results 18 months after the operation showed that no new stroke occurred during the follow-up period.The NIHSS scores in the patency group and the non-patency group were remarkably lower at 7 days,12,and 18 months after surgery than at admission(patency group:2[0,4],1[0,2],0[0,2]vs.3[0,6],respectively;the non-patency group:3[1,5],3[1,6],2[1,6]vs.4[1,7],respectively),with significant differences(all P＜0.05);However,the NIHSS scores in the patency group were significantly lower than that in the non-patency group at 12 and 18 months after surgery,and the proportion of patients with good prognosis in the patency group was substantially higher than that in the non-patency group(12months:87.1％[88/101]vs.4/8,P=0.039;18 months:90.1％[91/101]vs.4/8,P=0.025).Conclusion CDU can quantitatively evaluate the hemodynamic changes of bypass arteries after the STA-MCA bypass procedure,which can be applied to the long-term dynamic follow-up after the surgery.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Humans ; Tacrolimus/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Immunosuppressive Agents/therapeutic use* ; Treatment Outcome

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
China ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly/genetics* ; Thumb ; Whole Exome Sequencing

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Objective:To investigate the influence of HBV infection on the prevalence of fatty liver disease in Jinchang cohort and provide theoretical evidence for the prevention and treatment of fatty liver disease.Methods:Epidemiological investigation, laboratory examination and abdominal ultrasound were conducted in the baseline population of Jinchang cohort to collect the basic data, the differences in the prevalence of fatty liver disease under different HBV infection patterns were described and compared and the influence of different HBV infection patterns on the prevalence of fatty liver disease were evaluated by using logistic regression analysis.Results:The baseline Jinchang cohort population totaled 45 605, including 27 917 males and 17 688 females. The male to female ratio was 1.6∶1. The mean age of the overall population was 46.49 years. Among the 8 common HBV infection modes in the Jinchang cohort, the prevalence of fatty liver was low in HBsAg, HBeAg and HBcAb positive, HBsAg and HBcAb positive, and HBsAg, HBeAb and HBcAb positive groups. For 4 serum markers of HBV infection, the prevalence of fatty liver disease in HBsAg and HBeAg positive groups was lower than that in HBsAg and HBeAg negative groups. Logistic regression analysis showed that being HBsAg and HBcAb positive ( OR=0.61, 95% CI: 0.39-0.98) and HBsAg, HBeAg and HBcAb positive ( OR=0.52, 95% CI: 0.30-0.89) could reduce the risk for fatty liver disease. Conclusion:Acute HBV infection reduces the prevalence of fatty liver disease, and the reason may be related to the disturbance of the body's fat metabolism by active HBV replication.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.