Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives / 药学学报

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC50) and selectivity index (SI) values of 2.36 μmol·L-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (KD) value of 1.36 μmol·L-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Effect of fumigation therapy of Flos Farfarae in cigarette smoke-induced lung injury mice based on metabolomics / 药学学报

This study aimed to investigate the effect of Flos Farfarae (FF) fumigation on cigarette smoke-induced lung injury mice, and analyze the metabolic profile of lung tissue by metabolomics. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shanxi University (Approval number: SXULL2019014). By using HS-GC-MS to analyze volatile components of Flos Farfarae, 23 compounds were identified. The results showed that FF fumigation improved the lung tissue morphology of cigarette smoke-induced lung injury mice, lowered the levels of interleukin 6 (IL-6) and interleukin-1β (IL-1β). The lung tissue samples were applied for metabolomic analysis based on UHPLC-QTOF MS, the results showed that 70 metabolites were changed in the lung tissue of mice after cigarette exposure, and 35 of them could be regulated, including lysophosphatidylcholine (LPC), 12-HETE, adenosine, and xanthine. These metabolites, such as LPC, 12-HETE, adenosine, and xanthine were mainly associated with the body's inflammatory response. It was observed that these metabolites are primarily involved in purine metabolism, arachidonic acid metabolism, phospholipid metabolism, and pyruvate metabolism pathways. These findings suggest that the volatile terpenoids in the FF may regulate the metabolites associated with the inflammatory response in the lung tissue, such as lysophosphatidylcholine, 12-HETE, and adenosine, which could further alleviate lung inflammation induced by cigarette smoke through the metabolic pathways of purine metabolism and others. This study proved the scientific basis of the traditional application of FF fumigation, and provided a theoretical basis for the further product development.

Low BMI is Associated with Poor OI-IUI Outcomes in Patients with Unexplained Primary Infertility / 中山大学学报(医学科学版)

ObjectiveTo evaluate the effect of women's body mass index （BMI） on pregnancy outcomes of ovulation induction intrauterine insemination （OI-IUI） in patients with unexplained primary infertility. MethodsThe study included 764 OI-IUI cycles from January 2016 to December 2022 in reproductive center of Sun Yat-sen Memorial Hospital. According to BMI，patients were divided into three groups：low BMI （BMI<18.5 kg/m2）， normal BMI （18.5 kg/m2 ≤BMI＜23.0 kg/m2）， and high BMI （BMI≥23.0 kg/m2）. Comparison of clinical data and pregnancy outcomes was performed between the groups. Logistic regression was used to analyze the association between BMI and live birth rate. ResultsFrom the low BMI group to the high BMI group， the HCG positive rate （7.08%，9.74%， 13.19%）， clinical pregnancy rate（5.51%， 7.91%， 13.19%）， and live birth rate （4.72%， 6.90%， 12.50%） increased. Among them， the live birth rate of the high BMI group was significantly higher than that of the low BMI group and the normal BMI group， with a statistically significant difference （P=0.034）. While the early miscarriage rate （14.28%， 10.26%， 5.26%） decreased from the low BMI group to the high BMI group. The binary logistic regression analysis revealed that BMI was an independent factor in live birth， and high BMI resulted in a better live birth rate than low BMI （OR=3.15，95%CI=1.191-8.329，P=0.021）. ConclusionLow BMI is associated with poor OI-IUI outcomes in patients with unexplained primary infertility. These patients are encouraged to gain weight in a healthy manner.

Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Hearing loss and its relationship with blood pressure among workers exposed to noise in a brewery / 公共卫生与预防医学

Objective To investigate the health status of workers exposed to noise in a brewery in Beijing and to analyze the relationship between hearing loss and blood pressure. Methods A total of 949 noise-exposed workers in a brewery who participated in occupational health examination were selected as the investigation subjects. A survey was conducted to investigate the pure tone hearing threshold and abnormal blood pressure of the workers with different characteristics, and to analyze the relationship between the two. Results Among the noise-exposed workers, the detection rates of hearing abnormality, hypertension, and increased systolic and diastolic blood pressure were 73.55%, 52.37%, 43.84% and 46.47%, respectively. The detection rates of hearing abnormality, indicators of hypertension, high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average in males were higher than those in females (P 0.05), the detection rates of other hearing abnormality, indicators of hypertension, speech frequency hearing threshold abnormality, high frequency hearing threshold abnormality，increased binaural high frequency hearing threshold on average and the weighted value of the better ear's hearing threshold all increased or had an increasing trend with the increase of age or working years (P< 0.05). The detection rates of hypertension in the groups with high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average were higher than those in the normal group (P＜0.05). Conclusion The noise-exposed workers in the brewery have hearing impairment, which is related to the occurrence of hypertension. It is recommended to strengthen the publicity and education on noise protection and take protective measures to reduce the occurrence of occupational noise injury.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Second metabolites comparative analysis of Codonopsis pilosula (Franch.) Nannf. from different origins based on extensively targeted metabolomics / 药学学报

We performed an extensively targeting metabolomic detecting using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to compare the secondary metabolites in Dang shen [Codonopsis pilosula (Franch.) Nannf.] from Shanxi and Gansu provinces. The findings showed that 161 secondary metabolites in 6 groups (phenolic acids, flavonoids, lignans and coumarins, alkaloids, terpenoids, others) were found from Dang shen in Changzhi city of Shanxi province and Dingxi city of Gansu province. There were 98 secondary metabolites which is differed significantly. In comparison to Dingxi city, 33 different secondary metabolites of Dang shen in Changzhi city had a greater relative content, whereas relative content of 65 different metabolites in Dingxi city was higher. Metabolic pathway enrichment analysis revealed that phenolic acids and flavonoids were significantly different in the secondary metabolites of Dang shen from different producing places. This may be one of the reasons for the difference in the quality of Dang shen in Shanxi and Gansu provinces. This work compared and analyzed the secondary metabolites of Dang shen from Dingxi city in Gansu province and Changzhi city in Shanxi province for the first time, which lays the foundation for further study on the quality of Dang shen.

Effect of Chorionicity， Gestational Age at Birth and Birth Weight Discordance on Neonatal Outcomes in Twin Pregnancies / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of chorionicity， gestational age at birth and birth weight discordance on neonatal outcomes in twin pregnancies. MethodsWe conducted a population-based retrospective study of monochorionic diamniotic （MCDA） twin pregnancies and dichorionic diamniotic （DCDA） twin pregnancies who were admitted in the First Affiliated Hospital， Sun Yat-sen University from January 2015 to December 2020. A total of 1504 live-born twins were included， with 386 cases in MCDA group and 1118 cases in DCDA groups， respectively. The comparison of neonatal outcomes between MCDA and DCDA twins was performed using t-test， Wilcoxon rank sum test， Chi-square test or Fisher’s exact test. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight discordance and sex on neonatal outcomes. There were 168 live-born twins affected by inter-twin birth weight discordance≥25%， with 96 cases in MCDA group and 72 cases in DCDA groups， respectively. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight light or heavy （small twin or large twin） of the twin and sex on neonatal outcomes. ResultsAmong the 1 504 newborns， gestational age at birth was lower in MCDA group compared with DCDA group （P = 0.000）， and the degree of birth weight discordance was higher in MCDA group than that of the DCDA group （P = 0.001）. Birth asphyxia， respiratory distress syndrome （RDS）， bronchopulmonary dysplasia （BPD）， and sepsis were more frequency in MCDA group compared with DCDA group （P = 0.000， P = 0.000， P = 0.000， P = 0.000）. Low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis， necrotizing enterocolitis （NEC）≥stageⅡ， acute kidney injury （AKI）， retinopathy of prematurity （ROP）， and neonatal death respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.011， P = 0.000， P = 0.000， P = 0.000）. High degree of birth weight discordance was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP respectively （P = 0.045， P = 0.000， P = 0.000， P = 0.004， P = 0.017 ）. Chorionicity was not an independent risk factor for neonatal morbidity and death （P > 0.05）. Among the 168 twins with birth weight discordance ≥25%， low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP， respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.000）； small twin was an independent risk factor for birth asphyxia and BPD， respectively （ P = 0.013， P = 0.001）； chorionicity was not an independent risk factor for neonatal morbidity （P > 0.05）. ConclusionChorionicity was not an independent risk factor for adverse neonatal outcome in twin births. Low gestational age at birth and high degree of birth weight discordance were independent risk factor for adverse neonatal outcome in twin births. Small twins had increased risk of adverse neonatal outcome in twins with birth weight discordance ≥25%.

Changes in retinal peripheral refractive status and aberrations before and after femtosecond laser-assisted laser in situ keratomileusis and small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe and compare the changes in retinal peripheral refraction and aberrations after femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)versus small incision lenticule extraction(SMILE)for myopia correction.METHODS: A total of 71 patients(71 eyes)with myopia who underwent FS-LASIK from October 2022 to April 2023 in our hospital were selected as the FS-LASIK group, and 80 patients(80 eyes)with myopia who underwent SMILE were selected as the SMILE group. All patients underwent corneal wavefront aberration measurement and multispectral refractive topography preoperatively and 3mo postoperatively, as well as refraction difference value(RDV)in the range of 0°～10°, 10°～20°, 20°～30°, 30°～40°, and 40°～53° in the annulus of the retina, which were recorded as RDV-(0°～10°), RDV-(10°～20°), RDV-(20°～30°), RDV-(30°～40°), and RDV-(40°～53°). The results of two groups of patients were compared.RESULTS: No significant differences were observed in RDV-(0°～10°), RDV-(10°～20°), RDV-(20°～30°), RDV-(30°～40°), RDV-(40°～53°)between the two groups at 3mo post-operation(all P&#x003E;0.05). Furthermore, the RDV-(20°～30°), RDV-(30°～40°)and RDV-(40°～53°)of the two groups at 3mo postoperatively were all significantly lower than those preoperatively(all P&#x003C;0.05). The changes in coma(horizontal)and spherical aberration(SA)at 3mo postoperatively were smaller in the SMILE group [0.106(0.056, 0.171)and 0.115(0.081, 0.182)μm] than in the FS-LASIK group [0.206(0.104, 0.355)and 0.197(0.128, 0.254)μm](Z=-4.170, -5.016, all P&#x003C;0.05). A negative correlation was found between postoperative SA and postoperative RDV-(10°～53°)(rs=-0.205, -0.181, -0.226, -0.244, all P&#x003C;0.05).CONCLUSION: Both FS-LASIK and SMILE reduced retinal hyperopic defocus in the peripapillary macular range of 20°～53° eccentricity, and the postoperative changes in coma(horizontal)and SA were smaller with SMILE than with FS-LASIK. There was a certain correlation between postoperative SA and postoperative retinal peripheral defocus.

Naoxintong Capsules Treat Cardiac Injury after Cerebral Ischemia via TLR2/TLR4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveAfter the brain and heart injuries were simulated by myocardial injury caused by acute cerebral ischemia， this study explored the mechanism of Naoxintong capsules in treating brain and heart injuries under cerebral ischemia state with Toll-like receptor （TLR） 2/TLR4 as the breakthrough point. MethodC57BL/6 male mice were randomly assigned into the sham operation， model， Naoxintong， and Ginaton groups. The middle cerebral artery occlusion （MCAO） method was used to establish a mouse model of cerebral ischemia. The neuroethological score， cerebral infarction area， cell apoptosis， ionized calcium-binding adaptor molecule 1 （IBA-1）-positive microglia proportion， and serum levels of N-terminal pro-brain natriuretic peptide （NT-proBNP）， creatine kinase-MB （CK-MB）， and lactic dehydrogenase （LDH） were determined to evaluate the pharmacodynamic effects of Naoxintong capsules on heart and brain injuries after cerebral ischemia in mice. Western blotting was employed to determine the expression of TLR2/TLR4 protein in the brain and heart of mice. ResultCompared with the sham operation group， the model group showed increased cerebral infarction area， neuroethological score， apoptosis rate， IBA-1-positive microglia proportion， and serum levels of NT-proBNP， CK-MB， and LDH （P<0.01）. Naoxintong capsules reduced the cerebral infarction area， neuroethological score， apoptosis rate， IBA-1-positive microglia proportion （P<0.01）， and serum NT-proBNP and CK-MB levels （P<0.05） in mice compared with the model group. Western blotting results showed that Naoxintong Capsules down-regulated the expression levels of TLR2 （P<0.05） in the brain and TLR2 （P<0.01） and TLR4 （P<0.05） in the heart. ConclusionCerebral ischemia can cause myocardial damage， reflecting the pathological process of cardiac injury after cerebral ischemia. Naoxintong capsules can mitigate brain and heart injuries after cerebral ischemia and achieve the simultaneous treatment of the brain and the heart， in which TLR2/TLR4 plays a role.

Growth and intelligence development among a cohort of low birth weight infants / 中国学校卫生

Objective@#To explore growth and intelligence development of low birth weight infants (LBWI) at 24 and 36 months of age, so as to provide reference for early monitoring and intervention of the development of LBWI.@*Methods@#A total of 100 LBWI born and managed in Hefei Maternal and Child Health Care Institution were selected from 2012 October 1 to 2015 December 30, and 99 normal birth weight infants (NBWI) under child health management in the same sitinstitution were selected as controls. According a prospective cohort study method, and based on the establishment of a cohort and monitoring of childhood growth and development, a unified method was used to longitudinally follow up and observe the physical fitness of two groups of infants at the determined time points. The development of LBWI and NBWI at 24 and 36 months of age was surveyed using the Gesell Development Scale.@*Results@#Weight, length and head circumference of LBWI children at the age of 15-36 months were significantly lower than those of NBWI children ( P <0.05). In addition, 117 children (43.98%) completed the full assessment of intelligent development scale, including 62 LBWI and 55 NBWI. The scores of Gesell in NBWI group was higher than that in LBWI group at 24 and 36 months of age, including adaptability, gross motor, fine metor skills, language and personal social functions ( t =-4.17, -3.82, -3.21 , -3.03, -2.61; -4.23, -3.16, -3.07, -3.13, -3.99, P <0.05). Multivariate linear regression analysis found that birth weight was positively correlated with adaptability, gross motor, fine motor skills, language functions at 24 and 36 months of age and personal social function at 36 months of age ( β =0.004, 0.010; 0.003, 0.008; 0.003, 0.007; 0.004, 0.009; 0.011, P ＜0.05).@*Conclusion@#The growth and development of LBWI children are significantly delayed compared to NBWI children. The scores of LBWI children are lower than those of NBWI children in all functional areas. Weight is the main factor affecting children s intellectual development. Early monitoring and intervention of low birth weight infants should be carried out to avoid or mitigate adverse consequences.

Research Progress on Glypican-3 Targeted Therapy in Hepatocellular Carcinoma / 药学实践杂志

Liver cancer is the second leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the most common form of primary liver cancer. Glypican-3 (GPC3) is a cell membrane proteoglycan which is rarely expressed in normal adult tissues but is specifically upregulated in HCC, which makes GPC3 a reliable target for the diagnosis and treatment of HCC. The role of GPC3 in the regulation of cancer development through Wnt, YAP, hedgehog and other signaling pathways were reviewed in this article. GPC3-targeted therapies, such as monoclonal antibodies, bispecific antibodies, tumor vaccines, immunotoxins, CAR-T cells, and photosensitizer therapy were also summarized. These treatment methods offered promising approaches for HCC treatment and future treatment strategies for HCC based on GPC3 were prospected in this paper.

Efficacy analysis of simultaneous integrated boost intensity-modulated radiotherapy combined with chemotherapy in treatment of superior mediastinal lymph node metastasis after esophageal cancer surgery / 肿瘤研究与临床

Objective:To investigate the efficacy and adverse reactions of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with chemotherapy in the treatment of superior mediastinal lymph node metastasis after esophageal cancer surgery.Methods:The clinical data of 72 patients with concurrent chemoradiotherapy for superior mediastinal lymph node metastasis after esophageal cancer surgery in Tai'an Cancer Prevention and Treatment Hospital from January 2019 to May 2021 were retrospectively analyzed, and they were divided into intensity-modulated radiotherapy (IMRT) group (36 cases) and SIB-IMRT group (36 cases) according to different radiotherapy methods. The short-term efficacy, long-term survival rate and adverse reactions of the two groups were compared.Results:The response rate in the IMRT group was 66.7% (24/36), the response rate in the SIB-IMRT group was 86.1% (31/36), and the difference between the two groups was statistically significant ( χ2 = 3.77, P = 0.047). The 1-, 2- and 3-year overall survival rates in the IMRT group were 75.0%, 44.4% and 27.8%, and the 1-, 2- and 3-year overall survival rates in the SIB-IMRT group were 83.3%, 52.8% and 33.3%; the difference in the overall survival between the two groups was not statistically significant ( χ2 = 0.70, P = 0.401). There were statistical differences in the incidence of leukopenia, radiation esophagitis and radiation pleural gastritis between the two groups (all P < 0.05). There were no statistical differences in the incidence of radiation pneumonia and gastrointestinal reactions between the two groups (both P > 0.05). Conclusions:SIB-IMRT combined with chemotherapy in patients with superior mediastinal lymph node metastasis after esophageal cancer surgery has good local control rate and mild adverse reactions.

Clinical observation of contralateral needling combined with Maitland ankle mobilization for chronic ankle sprain / 针灸推拿医学（英文版）

Objective: To observe the efficacy of contralateral needling combined with Maitland ankle mobilization in the treatment of chronic ankle sprain.Methods: A total of 106 patients with chronic ankle sprain were included in the study. They were numbered according to their order of visit, with odd numbers assigned to the control group and even numbers assigned to the observation group, with 53 cases in each group. Patients in the control group were treated with Maitland ankle mobilization, while those in the observation group were given additional contralateral needling treatment. After treatment, we observed the indicators including, ankle circumference, range of motion (ROM) of dorsiflexion, ROM of plantar flexion, thickness of ankle ligaments, and the changes in Baird-Jackson ankle score, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS) score to compare the efficacy between the two groups. Results: After treatment, the total effective rate of the observation group was 94.3％ and was significantly higher than that of the control group (81.1％), indicating statistical significance (P<0.05). After treatment, the ankle circumference of both groups decreased, and the ROM of dorsiflexion and the ROM of plantar flexion increased (P<0.05). The changes in the observation group were more significant, indicating inter-group statistical significance (P<0.05). After treatment, the thickness of the anterior talofibular ligament, calcaneofibular ligament, and posterior talofibular ligament, as well as the VAS scores decreased in both groups; the changes in the observation group were more significant, indicating inter-group statistical significance (P<0.05). After treatment, the Baird-Jackson ankle score and the AOFAS ankle- hindfoot score increased in both groups, and the scores in the observation group were higher than those in the control group, indicating inter-group statistical significance (P<0.05). Conclusion: The efficacy of contralateral needling combined with Maitland ankle mobilization in the treatment of chronic ankle sprain is superior to that of Maitland ankle mobilization alone.

Advances in the establishment and evaluation of animal models of secondary lymphedema / 中华显微外科杂志

Secondary lymphedema is a chronic progressive disease caused by the obstruction of lymphatic reflux, which leads to a series of secondary affection. There is no cure at present. Exploring the pathogenesis and treatment of lymphedema is based on animal models that mimic the pathophysiology of chronic lymphedema in humans. Currently, there are many known animal models of lymphedema, such as the limb lymphedema model of mice, dogs and other animals, and the rabbit ear lymphedema model. But most of them cannot induce the persistent and stable lymphedema temporarily, which lead to a deadlock in the related research progress. Therefore, it is necessary to improve and even create new animal models of lymphedema. This paper summarises the progress of relevant literature and provides references for further improving the establishment of a lymphedema animal model. It also summarise existing methods for evaluating lymphedema or lymphatic vessel function to provide an evaluation tool for modified or new animal models.

Prenatal phenotypic analysis and genetic counseling for 22q11.21 microdeletion and microduplication syndrome / 中华围产医学杂志

Objective:To analyze the prenatal clinical phenotypes and pregnancy outcomes of fetuses with 22q11.21 microdeletion and microduplication syndrome to provide a basis for clinical genetic counseling.Methods:This retrospective study involved the cases diagnosed with 22q11.21 microdeletion or microduplication by chromosomal microarray analysis (CMA) due to abnormal ultrasound findings, advanced maternal age, or high-risk pregnancies indicated by serum screening in the Prenatal Diagnosis Center of the First Affiliated Hospital of Air Force Medical University from January 2015 to January 2022. Clinical phenotypes and pregnancy outcomes of the fetuses were analyzed and described.Results:Among 9 141 cases referred for CMA during the study period, 77 cases (0.8%) were diagnosed as 22q11.21 microdeletion or microduplication, including 62 (80.5%) with 22q11.21 microdeletion and 15 (19.5%) with microduplication. In the 22q11.21 microdeletion cases, 58 had typical deletion, and four had atypical deletions, but all fetuses carried TBX1 gene that was clearly associated with congenital heart disease. The 15 fetuses with 22q11.21 microduplication including 14 in the typical region and one in the atypical region. Forty-eight (77.4%) out of the 62 fetuses with 22q11.21 microdeletion were complicated by congenital heart defects, including 28 with conotruncal defects. Five of the 15 fetuses with 22q11.21 microduplication were complicated by congenital heart defects. The cases were followed up on telephone at three to six months after the expected date of delivery. Among the 62 cases with 22q11.21 microdeletion, 52 terminated pregnancies, five were lost to follow-up, and five were delivered (one died after one month of premature delivery, one was born with anal advancement and growth retardation, and three were followed up without obvious abnormality). Among the 15 cases with 22q11.21 microduplication, four terminated pregnancies, two were lost to follow-up, and nine gave birth (eight were followed up without obvious abnormality, one grew slowly). Conclusions:The application of CMA in the prenatal diagnosis of 22q11.21 microdeletion and microduplication fetuses, and the comprehensive analysis of clinical manifestations and pregnancy outcome combined with ultrasonic diagnosis are of great significance in guiding the treatment and rehabilitation after birth of an affected child. Genetic counseling for cases with 22q11.21 microdeletion and microduplication syndrome should be cautious and consider ultrasound findings.

Percutaneous kyphoplasty assisted by three dimensional printing percutaneous guide plate for the treatment of osteoporotic vertebral compression fractures / 中国骨伤

OBJECTIVE@#To verify the safety of three dimensional printing percutaneous guide plate assisted percutaneous kyphoplasty(PKP) in the treatment of osteoporotic vertebral compression fractures(OVCFs).@*METHODS@#The clinical data of 60 patients with OVCFs treated by PKP from November 2020 to August 2021 were retrospectively analyzed. There were 24 males and 36 females, aged from 72 to 86 years old with an average of (76.5±7.9) years. Routine percutaneous kyphoplasty was performed in 30 cases (conventional group) and three dimensional printing percutaneous guide plate assisted PKP was performed in 30 cases (guide plate group). Intraoperative pedicle puncture time (puncture needle to posterior vertebral body edge) and number of fluoroscopy, total operation time, total number of fluoroscopy, amount of bone cement injection, and complication (spinal canal leakage of bone cement) were observed. The visual analogue scale (VAS) and the anterior edge compression rate of the injured vertebra were compared before operation and 3 days after operation between two groups.@*RESULTS@#All 60 patients were successfully operated without complication of spinal canal leakage of bone cement. In the guide plate group, the pedicle puncture time was(10.23±3.15) min and the number of fluoroscopy was(4.77±1.07) times, the total operation time was (33.83±4.21) min, the total number of fluoroscopy was(12.27±2.61) times;and in the conventional group, the pedicle puncture time was (22.83±3.09) min and the number of fluoroscopy was (10.93±1.62) times, the total operation time was(44.33±3.57) min, the total number of fluoroscopy was(19.20±2.67) times. There were statistically significant differences in the pedicle puncture time, intraoperative number of fluoroscopy, the total operation time, and the total number of fluoroscopy between the two groups(P<0.05). There was no significant difference in amount of bone cement injection between the two groups(P>0.05). There were no significant differences in VAS and the anterior edge compression rate of the injured vertebra at 3 days after operation between two groups(P>0.05).@*CONCLUSION@#Three dimensional printing percutaneous guide plate assisted percutaneous kyphoplasty is safe and reliable, which can reduce the number of fluoroscopy, shorten the operation time, and decrease the radiation exposure of patients and medical staff, and conforms to the concept of precise orthopaedic management.

The research progress of high altitude environment-associated chronic obstructive pulmonary disease and therapeutic drugs / 生理学报

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality. The therapeutic window of theophylline drugs for COPD is narrow, and the high altitude environment has an influence on the pharmacokinetics of the drugs. This review summarizes the differences in the prevalence, mortality, clinical manifestation and clinical symptoms of COPD in the plateau and plain, providing a basis for identifying the risk factors of COPD in the plateau areas. The effects of plateau hypoxic environment on the pharmacokinetics of COPD drugs were also discussed. It can provide a rationale for more effective prevention and treatment of COPD at high altitude.