Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs.

Background: It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods: Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results: Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13-27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions: Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.

Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications.

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p=0.044) and heart (p=0.001) components at the M1 and M5 regions (p=0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p=0.049) and myogenic (p=0.032) components at the M1 region, as well as in the endothelial (p<0.001) component at the M5 region and in the myogenic component at the dorsal foot (p=0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region (p=0.050) and heel area (p=0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p=0.017) and heel area (p=0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

Effects of nobiletin on gut microbiota and short-chain fatty acids in rats with simple obesity / 中国病理生理杂志

AIM:This study aims to investigate the impact of nobiletin(NOB)on the gut microbiota and short-chain fatty acids(SCFAs)in high-fat diet-induced obese rats.METHODS:A total of 22 SD rats were randomly di-vided into the control(CON)group and high-fat diet(HFD)group.The HFD induced obesity,upon successful modeling,the rats were further divided into the HFD and NOB group,each group consisting of 6 rats.The NOB group received nobi-letin solution(100 mg·kg-1·d-1)via gavage for 21 consecutive days.Body weight was measured bi-daily,and hematoxylin-eosin(HE)staining was employed to observe pathological changes in adipose tissue and liver.Serum lipid levels were as-sessed using an auto-biochemical analyzer.Analysis of the gut microbiota was performed using 16S ribosomal RNA(rRNA)sequencing,while high-performance liquid chromatography mass spectrometry(LC-MS)was used to determine SCFAs levels in rat feces.RESULTS:Compared with CON group,HFD-fed demonstrated a substantial increase in body weight(P<0.01),accompanied by an augmentation in adipocyte diameter and the presence of hepatic cell vacuolization,indicative of cellular steatosis and inflammation.Moreover,there was a notable elevation in TG and TC levels(P<0.05).At the phylum level,the HFD rats exhibited an altered composition,characterized by an increase in Firmicutes and a con-current decrease in Bacteroidetes.At the genus level,Bacteroides,Lactobacillus and Blautia experienced a significant de-crease,while Colidextribacter showed an increase.Notably,there was a substantial reduction in the expression of propion-ic acid and butyric acid.In comparison to the HFD group,rats administered with NOB demonstrated a marked decrease in body weight(P<0.05),a reduction in adipocyte diameter,and an amelioration in hepatic cell vacuolization and cellular steatosis.Furthermore,TG and TC levels exhibited a significant decrease(P<0.05).At the phylum level,Firmicutes de-creased,and Bacteroidetes increased.At the genus level,Bacteroides,Lactobacillus and Blautia exhibited a significant in-crease,while Colidextribacter displayed a decrease.Additionally,there was an up-regulation of propionic acid and butyric acid levels in the NOB group.CONCLUSION:Nobiletin,through its multifaceted actions,demonstrates a potential anti-obesity effect by effectively reducing body weight in obese rats.This includes the regulation of gut microbiota structure,modulation of SCFAs content,and enhancement of lipid metabolism.

Effects of PM2.5 and heat/cold exposure on AKT/GLUT4 pathway in mouse skeletal muscle and white adipose tissue / 环境与职业医学

Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (TN-FA), a normal temperature-concentrated PM2.5 group (TN-PM), a heat-filter air group (TH-FA), a heat-concentrated PM2.5 group (TH-PM), a cold-filter air group (TC-FA), and a cold-concentrated PM2.5 group (TC-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the TN-PM mice compared to the TN-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.

Study on apoptosis mechanism of Jurkat cells induced by CAHB in adult acute lymphoblastic leukemia / 中国现代医生

@#Objective To explore the mechanism of apoptosis induced by diacetyl hexamethylene diamine(CAHB)in adult acute lymphoblastic leukemia Jurkat cells,and to provide theoretical basis for the clinical application of CAHB.Methods Annexin V+/PI-cell rate of Jurkat cells after CAHB induction was analyzed by flow cytometry.The Annexin V+/PI-cell rate was observed after treatment with caspase-9 inhibitor Z-LEHD-FMK.The expressions of apoptosis-related proteins caspase-8,caspase-9 and caspase-3 were observed by Western blotting.Results After CAHB induction,Jurkat cells were reduced in size,cell membrane crinkling,chromatin thickening,nuclear pyknosis or fragmentation,etc.Typical apoptotic bodies could be seen.CAHB induced Jurkat cell apoptosis by activating caspase-9 and caspase-3 in a dose-effect and time-dependent manner.Caspase-9 inhibitors could inhibit apoptosis induction of CAHB to a certain extent.Conclusion CAHB induced Jurkat cell apoptosis was related to caspase-9 and caspase-3 activation.

Is a Preoperative MRI Scan Necessary for Acute Achilles Tendon Rupture?

BACKGROUND: Different treatment methods have been developed for acute Achilles tendon rupture (ATR), including conservative treatment, minimally invasive or transdermal surgery, and open surgery, and there is no consensus about which method is superior. It is important to clarify the presence of Achilles tendon (AT) degeneration, the rupture site, and the rupture shape before surgery to determine whether minimally invasive or open surgery should be selected, thereby reducing the re-rupture rate following acute ATR. The aim of this study was to investigate the diagnostic value of MRI in identifying the presence of AT degeneration, the rupture site, and the rupture shape for acute closed ATR. METHODS: From January 2016 to December 2019, patients with acute closed ATR who had undergone repair surgery were retrospectively enrolled. All patients received MRI examination, and the distance between the insertion site and broken end and the rupture shape (types I, II, and III) were independently determined by two observers. Then, the stump of the AT was exposed during the operation. The rupture site and rupture shape were recorded and compared and analyzed with the MRI results. Consistency analyses (using Cohen's kappa coefficient or intraclass correlation coefficient-ICC) and calculation of diagnostic performance indexes were, respectively, conducted to evaluate the diagnostic value of the MRI. RESULTS: This study included 47 consecutive patients with acute ATR, with an average age of 38.4 years. Among them, 40 were male, and seven were female. The intraoperative exploration demonstrated a total of 34 (72.3%), 10 (21.3%), and three (6.4%) patients with type I, II, and III ruptures, respectively. The average distance between the insertion site and the proximal broken end measured intraoperatively was 4.07 ± 1.57 cm. High or excellent consistencies were found for ATR classifications (kappa: 0.739-0.770, p < 0.001) and rupture sites (ICC: 0.962-0.979, p < 0.001) between two observers and between observers 1 and 2 and intraoperative findings. Tendinopathy was identified in 22 patients by MRI and confirmed during surgery. CONCLUSIONS: MRI scanning of acute closed ATR can help determine whether there is degeneration of the AT, as well as the location and shape of the rupture, which can guide the selection of the optimal operation method for orthopedic surgeons. Therefore, it is necessary to take preoperative MRI scans for patients with acute Achilles tendon ruptures.

[Protective mechanism of electroacupuncture combined with acellular nerve allografts on spinal ganglia in rats with sciatic nerve injury].

OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groups， with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structure， the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen / 中华流行病学杂志

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

Clinical application of acupuncture-moxibustion for the treatment of spirit based on approximate entropy of electrooculogram signal / 中国针灸

According to the theory of acupuncture-moxibustion for the treatment of spirit, starting from the relationship between eye movement and spirit, the application of electrooculogram (EOG) signal acquisition and analysis technology for the clinical treatment of spirit by acupuncture-moxibustion is discussed. Based on the nonlinear dynamic characteristics of EOG signals, it is proposed to apply the approximate entropy algorithm to extract the EOG signal characteristics in autism spectrum disorder children under different behavior states, which could realize the preliminary exploration of the correlation between EOG signals and cognitive activities. This could provide a possibility to objectively reflect the patient' s current mental state, and could be used as a potential method to grasp spirit in clinical acupuncture- moxibustion treatment. Furthermore, considering the characteristics of acupoint stimulation on the body surface, the EOG signal acquisition and analysis technology could further be combined with biofeedback technology, and a new idea for clinical acupuncture-moxibustion to treat spirit guided by biofeedback of EOG is proposed.

Short-term efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for the treatment of non-small cell lung cancer / 中国胸心血管外科临床杂志

@#Objective    To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods    The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results    After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion    Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.

Transcutaneous electrical acupoint stimulation based on electro-oculogram signal regulation for children with mental retardation: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) at Changqiang (GV 1) based on the modulation of electro-oculogram (EOG) signal for children with mental retardation, and explore the evaluation effect of the goal attainment scale (GAS) in children with mental retardation.@*METHODS@#Sixty children with mental retardation were randomly divided into a treatment group and a control group, with 30 cases in each one. The children in the control group were treated with conventional rehabilitation, 5 times a week. On the basis of the control group, TEAS at Changqiang (GV 1) under the modulation of EOG signal was adopted in the treatment group. When the similarity between the collected EOG signal and the template was within the range of EOG threshold, one electric stimulation was triggered at Changqiang (GV 1) for 20 s (continuous wave, 70-100 Hz in frequency, 0.1-0.2 ms in pulse width), lasting 30 min in each treatment, the intervention was given twice a week. One course of treatment was composed of 4 weeks, and 3 courses were required in total in the two groups. The infant-junior high school student's social living ability scale (S-M) and GAS were scored and compared before and after treatment in the two groups.@*RESULTS@#After treatment, the scores of self-living ability in the treatment group and communication ability in the control group were higher than those before treatment (P<0.01, P<0.05). The scores of collective activity and motor ability in the treatment group were higher than those in the control group (P<0.05). After treatment, GAS scores were higher than before treatment in both groups (P<0.001), and the score in the treatment group was higher than the control group (P<0.05).@*CONCLUSION@#TEAS under the modulation of EOG signal is conductive to improving the collective, motor and self-living abilities of the children with mental retardation and promoting children's individual goals. Compared with the standard score of S-M, the T value of GAS can better reflect the subtle progress of individual.

Application of meridian and acupoint diagnosis of three yin meridians of foot in the treatment for gynecological diseases with acupuncture and moxibustion / 中国针灸

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.

Effect and mechanism of Xihuang Pills on rats with precancerous lesions of breast / 中国中药杂志

The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.

Analysis of clinical features and PAK1 gene variant in a child with epilepsy and global developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical phenotype and genetic basis of a child with epilepsy and global developmental delay.@*METHODS@#A child with epilepsy and global developmental delay who had visited West China Second University Hospital, Sichuan University on April 1, 2021 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. A literature review was also carried out by searching databases such as Wanfang data knowledge service platform, China National Knowledge Infrastructure, PubMed, ClinVar and Embase to summarize the clinical phenotypes and genotypes of the affected children.@*RESULTS@#The child was a 2-year-and-2-month-old male with epilepsy, global developmental delay and macrocephaly. Results of WES showed that the child has harbored a c.1427T>C variant of the PAK1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Only one similar case had been recorded by the dbSNP, OMIM, HGMD, and ClinVar databases. No frequency for this variant among Asian population was available in the ExAC, 1000 Genomes, and gnomAD databases. Prediction with IFT, PolyPhen-2, LRT, Mutation Taster, and FATHMM online software suggested that this variant is deleterious to the function of encoded protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the PAK1 gene c.1427T>C variant was determined to be likely pathogenic.@*CONCLUSION@#The PAK1 gene c.1427T>C variant probably underlay the epilepsy and global developmental delay in this child, which has provided a reference for the clinical diagnosis and genetic counseling in children with similar disorders.

Exploring the application value of the modified Delphi method in the development process of acupuncture and moxibustion guideline recommendations based on the WFAS Clinical Practice Guideline for Female Urinary Incontinence / 中国针灸

Taking the recommendations development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) standard Clinical Practice Guideline for Female Urinary Incontinence as an example, this study analyzed the consensus expert composition, specific consensus process, and results in the development of the guideline's recommendations. It systematically examined the advantages of using the modified Delphi method in the formation of recommendations for acupuncture and moxibustion clinical practice guideline, with the aim of providing reference for the development of acupuncture and moxibustion guidelines in the same field.

Elevated level of high-sensitivity cardiac troponin I as a predictor of adverse cardiovascular events in patients with heart failure with preserved ejection fraction / 中华医学杂志(英文版)

BACKGROUND@#The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear. This study investigated the association between the extent of elevated levels of high-sensitivity cardiac troponin I (hs-cTnI) and the prognosis in heart failure with preserved ejection fraction patients.@*METHODS@#A retrospective cohort study consecutively enrolled 470 patients with heart failure with preserved ejection fraction from September 2014 to August 2017. According to the level of hs-cTnI, the patients were divided into the elevated level group (hs-cTnI >0.034 ng/mL in male and hs-cTnI >0.016 ng/mL in female) and the normal level group. All of the patients were followed up once every 6 months. Adverse cardiovascular events were cardiogenic death and heart failure hospitalization.@*RESULTS@#The mean follow-up period was 36.2 ± 7.9 months. Cardiogenic mortality (18.6% [26/140] vs. 1.5% [5/330], P <0.001) and heart failure (HF) hospitalization rate (74.3% [104/140] vs. 43.6% [144/330], P <0.001) were significantly higher in the elevated level group. The Cox regression analysis showed that the elevated level of hs-cTnI was a predictor of cardiogenic death (hazard ratio [HR]: 5.578, 95% confidence interval [CI]: 2.995-10.386, P <0.001) and HF hospitalization (HR: 3.254, 95% CI: 2.698-3.923, P <0.001). The receiver operating characteristic curve demonstrated that a sensitivity of 72.6% and specificity of 88.8% for correct prediction of adverse cardiovascular events when a level of hs-cTnI of 0.1305 ng/mL in male and a sensitivity of 70.6% and specificity of 90.2% when a level of hs-cTnI of 0.0755 ng/mL in female were used as the cut-off value.@*CONCLUSION@#Significant elevation of hs-cTnI (≥0.1305 ng/mL in male and ≥0.0755 ng/mL in female) is an effective indicator of the increased risk of cardiogenic death and HF hospitalization in heart failure with preserved ejection fraction patients.

Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor / 中国中药杂志

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.