OBJECTIVE To promote the application of drones in emergency rescue and related fields， expand “low-altitude+ medical” rescue services， and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones （2025 Edition） （hereinafter referred to as the Consensus） was jointly initiated by the Division of Therapeutic Drug Monitoring， Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit， organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline， resulting in a preliminary draft. Delphi method was employed， and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated， the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose， principles， and applicable scenarios， basic requirements， and operational procedures for low-altitude transport and delivery of emergency medications； distribution requirements and precautions for controlled substances， fragile medications， and temperature-sensitive medications； and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Objective:To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics. Methods:LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children′s Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethic Committee of the Fujian Children Hospital(Ethic No. 2022ETKLR10024).Results:Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes by LRS. The most common type of fused CYP21A1P/ CYP21A2 gene was CH-1 (61.5%), and 1 (3.3%) was found to harbor TNXA/ TNXB CH-1. 11 cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (61.5%), which was followed by CYP21A2 exons 1-7 del (23.1%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/ TNXB CH-1 had presented with CAH-X syndrome. Conclusion:Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.

Objective:To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics. Methods:LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children′s Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethic Committee of the Fujian Children Hospital(Ethic No. 2022ETKLR10024).Results:Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes by LRS. The most common type of fused CYP21A1P/ CYP21A2 gene was CH-1 (61.5%), and 1 (3.3%) was found to harbor TNXA/ TNXB CH-1. 11 cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (61.5%), which was followed by CYP21A2 exons 1-7 del (23.1%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/ TNXB CH-1 had presented with CAH-X syndrome. Conclusion:Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.

Objective To compare the fetal imaging quality in different positions and the maternal comfort level in a super large-bore magnet,so as to estimate the application value of left lying position scanning in fetal brain MRI.Methods A total of 32 pregnant women in the third trimester who underwent fetal brain imaging in a super large-bore magnet(75cm)were collected.Each subject completed left lying position and supine position scanning and scored the comfort of the two.Radiologists scored the image subjectively,and objectively measured signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of fetal brain images.Results The comfort score of the left lying position(4.3±0.7)was higher than that of the supine position(3.4±0.7),and the difference was statistically significant(P＜0.001).The subjective score showed that there was no significant difference between the left lying position and the supine position in terms of brain image quality(P＞0.05),which could meet the needs of clinical diagnosis.The objective score showed that SNR of midbrain in left lying position was higher than in supine position(P＜0.05).The CNR of left occipital lobe in left lying position was higher than in supine position(P＜0.05).Conclusion In super large-bore magnet,left lying position scanning is a safe and pregnancy-friendly option that can not only improve maternal comfort level,but also improve fetal brain imaging.

Objective:To compare the safety and efficacy of terbutaline and nifedipine for acute intrapartum fetal resuscitation (IUFR).Methods:This was a prospective randomized controlled study involving 110 pregnant women with non-reassuring fetal heart rate tracings (NRFHT) during delivery at Guangzhou Women and Children's Medical Center between January and April 2021. These women were randomly allocated to receive subcutaneous terbutaline sulphate (0.25 mg, terbutaline group) or oral nifedipine (10 mg, nifedipine group), with 55 subjects in each group. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation before and 5, 15 and 30 min after treatment as well as the success rate of intrapartum resuscitation, the onset time of medication, and the incidence of postpartum hemorrhage were analyzed using t test, Chi-square test or Fisher's exact test. Results:Two groups both showed no significant difference in the mean arterial pressure or oxygen saturation before or after treatment (all P>0.05). The heart rate was not affected in nifedipine group at any time points ( P>0.05). While the patients treated with terbutaline showed accelerated maternal heart rate 5, 15 and 30 min after administration as compared with the baseline[(97.0±20.2), (99.2±13.8), (91.8±12.6) vs (81.7±11.3) bpm, all P<0.001], but it began to decrease at 30 min, with a drop of 6.4 bpm compared with that at 15 min (95% CI: 1.5-11.2, P<0.05). None of the pregnant women had adverse reactions requiring medical intervention. The rates of successful acute resuscitation were similar in the two groups [terbutaline: 78.2% (43/55) vs nifedipine: 70.9% (39/55), χ 2= 0.77, P=0.381]. Terbutaline had a shorter onset time than nifedipine in slowing the frequency of contractions and returning fetal heart rate to class Ⅰ category [2(1-6) vs 6(1-10) min, U=2 348.50, P<0.001]. No significant difference was found between the two groups in terms of NRFHT-indicated cesarean section, assisted vaginal delivery, or second dose of tocolysis within 1 h (all P>0.05) nor in blood loss volume, postpartum hemorrhage rate, low Apgar score, low umbilical artery pH value (pH<7.2), neonatal asphyxia rate, or neonatal intensive care admission rate (all P>0.05). Conclusion:Terbutaline spends less time than nifedipine to take effect and may be an alternative for acute IUFR without significant adverse outcomes.

Objective:To investigate the clinical characteristics of vasa previa (VP) with low-lying placenta (LP).Methods:A retrospective case-control study was conducted on pregnant women with VP who delivered at Guangzhou Women and Children's Medical Center from January 2015 to August 2021. According to the status of LP, these cases were classified into VP with LP (VP+LP) and VP without LP (VP-LP) group. The cases diagnosed with placenta previa (PP, n=128) during the same period were collected as control. Maternal-fetal clinical characteristics and outcomes were compared among the three groups using t-test, Mann-Whitney U test, and Chi-square test (or Fisher's exact test). Results:During the study period, 116 VP cases were diagnosed, accounting for 0.085% (116/136 450) of all deliveries. Apart from one case of intrauterine death caused by non-VP reasons in the third trimester, there were 64 in the VP+LP group and 51 in the VP-LP group. VP+LP cases accounted for about 2.9% (64/2 219) of all the cases with PP or LP. The proportions of multiparae and women with a history of cesarean section were significantly higher in the VP+LP group than in the VP-LP group [62.5% (40/64) vs 39.2% (20/51), χ 2= 6.17, P=0.013; 31.3% (20/64) vs 13.7% (7/51), χ 2= 4.85, P=0.028]. Besides, a rare type of VP (type Ⅲ) was only found in the VP+LP group (9.4%, 6/64). The median gestational age at first diagnosis by prenatal ultrasound was significantly larger in the VP+LP group than in the VP-LP group [28.3 (23.6-31.7) vs 23.9 (23.3-25.9) weeks, Z=2.61, P=0.007]. There was no significant difference in the incidence of antepartum hemorrhage between the two groups. In contrast, the amount of postpartum hemorrhage was significantly increased in the VP+LP group [550 (436-732) vs 420 (300-540) ml, Z=3.37, P=0.001]. Compared with the VP-LP group, the VP+LP group showed a lower incidence of lower neonatal Apgar score (<7 at 5 min) and hypoxic-ischemic encephalopathy [0.0%(0/64) vs 6.9%(4/58), 0.0%(0/64) vs 8.6% (5/58), Fisher's exact test, both P<0.05]. No neonatal death was reported in the VP+LP and VP-LP groups. No significant difference in the incidence of antepartum hemorrhage was found between the VP+LP group and the PP group. Still, the median time at delivery was earlier [36.0 (34.3-36.9) vs 37.0 (35.7-37.3) weeks, Z=3.79, P<0.001], and the incidence of abnormal fetal heart rate was higher [10.9% (7/64) vs 3.1% (4/128), Fisher's exact test , P=0.044] in the VP+LP group. Furthermore, the neonatal NICU admission rate and the incidence of respiratory distress syndrome were significantly higher in the VP+LP group than in the PP group [36.4% (24/66) vs 12.1% (16/132), χ 2= 16.04, P<0.001; 25.8% (17/66) vs 12.1% (16/132), χ 2= 5.89, P=0.015]. Conclusions:For VP+LP cases, there might be an additional type (type Ⅲ VP). Patients with VP+LP would have more blood loss within 24 h after delivery and a higher risk of adverse neonatal outcomes. Intensive attention should be paid to those diagnosed with LP during the third trimester to identify any VP.

Triterpenoids are a class of natural products of great commercial value that are widely used in pharmaceutical, health care and cosmetic industries. The biosynthesis of triterpenoids relies on the efficient synthesis of squalene epoxide, which is synthesized from the NADPH dependent oxidation of squalene catalyzed by squalene epoxidase. We screened squalene epoxidases derived from different species, and found the truncated squalene epoxidase from Rattus norvegicus (RnSETC) showed the highest activity in engineered Escherichia coli. Further examination of the effect of endogenous cytochrome P450 reductase like (CPRL) proteins showed that overexpression of NADH: quinone oxidoreductase (WrbA) under Lac promoter in a medium-copy number plasmid increased the production of squalene epoxide by nearly 2.5 folds. These results demonstrated that the constructed pathway led to the production of squalene epoxide, an important precursor for the biosynthesis of triterpenoids.
Animals ; Escherichia coli/genetics* ; NADPH-Ferrihemoprotein Reductase ; Protein Engineering ; Rats ; Repressor Proteins ; Squalene ; Squalene Monooxygenase/genetics*

The cross-fusion research of artificial intelligence technology and spinal surgery represented by machine learning and neural network model is a new research direction and hot issue in the field of artificial intelligence in recent years. The anatomy and disease symptoms of the spine are complex, and the diagnosis and treatment of spinal surgery require rich clinical experience. However, the distribution of medical resources in China is seriously uneven. How to improve the ability of primary medical services so that the most extensive patient groups can benefitis still an urgent problem to be solved. Artificial intelligence is a technical science that researches and develops theories, methods, technologies, and application systems for simulating, extending and expanding human intelligence. With the advent of the era of big data medical technology, artificial intelligence technology may solve this problem by transforming "experts sinking" into "tech sinking" . At present, technologies such as confrontation learning, weakly supervised learning, intensive learning and graph neural networks have become research hotspots in the field of artificial intelligence, and have also played an important role in many fields of clinical medicine. Based on the advantages of deep learning and neural network in disease learning, many spine surgeons combine it with the diagnosis and treatment of cervical spondylosis, low back pain, lumbar degenerative diseases, spinal deformity, spinal tumors, and other spine-related diseases. The rapid location and accurate diagnosis of the disease not only makes it an effective tool for the comprehensive diagnosis of spinal diseases but also provides the basis for the most reasonable treatment options for spinal diseases. In the domestic application of artificial intelligence in the diagnosis and treatment of spinal surgery, it can also solve the problems of difficult diagnosis and complicated treatment of spinal diseases faced by primary doctors, reduce the rate of misdiagnosis and missed diagnosis, and effectively reduce the economic and social burden of spinal diseases. This paper reviews the research progress of artificial intelligence represented by deep learning in the field of diagnosis and treatment of spinal surgery at home and abroad, and the advantages and application prospects of artificial intelligence in the diagnosis and treatment of spinal surgery.

Objective To assess the influences of early implementation of patient-controlled epidural analgesia (PCEA) in labor on uterine myoelectrical activity and delivery outcomes. Methods A prospective study was conducted on 240 singleton cephalic primiparae with spontaneous labor at Guangzhou Women and Children's Medical Center from January 2015 to October 2018. Those women, who were ready to accept PCEA, were randomly assigned to early- or late-PCEA group based on cervical dilation of 0-3 cm or 3-6 cm at the time of commencing PCEA, while those who refused PCEA in labor were classified as non-PCEA group. Uterine electromyographic activity and visual analogue score (VAS)were recorded before and 1 h and 2 h after PCEA. Patient satisfaction with labor, duration of the first stage of labor, volume of postpartum bleeding within 2 h after delivery and neonatal Apgar score were compared between different groups using multivariate analysis of variance, repeated measures analysis of variance, LSD-t test or Chi-square test. Results The VAS values 1 h after PCEA in the early- and late-PCEA group were both lower than that in the non-PCEA group (2.08±1.34 and 2.00±1.28 vs 7.65±1.04, LSD-t were － 27.713 and － 27.663, P<0.001) and those before PCEA (7.65±0.91 and 7.62±0.86, LSD-t were －32.879 and －33.349, P<0.001). The VAS values 2 h after PCEA in the early- and late-PCEA group were both lower than that in the non-PCEA group (1.63±1.53 and 1.41±1.56 vs 7.66±0.87, LSD-t were －27.018 and －27.823, P<0.001) and those before PCEA (LSD-t were －31.379 and －32.718, P<0.001).The patient satisfaction rate with labor was higher in the early-PCEA group comparing to the late-PCEA group [80.0% (72/90) vs 61.1% (55/90), P<0.001], and the two figures above were both higher than that of the non-PCEA group [20.0% (12/60), both P<0.001]. There was no significant difference in the duration of the first stage of labor, the volume of postpartum blood loss 2 h after delivery, oxytocin usage rate, the rate of convertion to cesarean section, neonatal birth weight or Apgar score at 1 or 5 min among the three groups (all P>0.05). There was also no significant difference in uterine electromyographic parameters among the three groups before or 2 h after PCEA (all P>0.05). The number and duration of burst, power density spectrum peak frequency, root mean square and total power 1 h after PCEA in the early- and later-PCEA group were all lower than those in the non-PCEA group [4.80±2.49 and 5.54±3.04 vs 9.67±2.44; (34.41±1.21) and (36.94±1.18) vs (41.68±1.53) s; (0.36±0.08) and (0.36±0.07) vs (0.48±0.05) Hz ; (0.05±0.04) and (0.05±0.05) vs (0.07±0.05) mV; (4.33±0.51) and (5.36 ±0.59) vs (9.90±1.43) pV2; all P<0.05]. Conclusions The effect of PCEA on uterine myoelectrical activity has no association with the commencing time. While early PCEA could alleviate the labor pain as soon as possible, which enable us to improve the efficacy of labor analgesia, patient satisfaction and maternal and neonatal safety without increasing cesarean section rate.