Objective:To investigate the hemodynamic changes in the ascending aorta (AAo) before and after interventricular septal myocardial resection in obstructive hypertrophic cardiomyopathy (HOCM) using cardiac magnetic resonance four-dimensional blood flow (CMR 4D Flow) technology.Methods:HOCM patients who underwent interventricular septal myocardial resection at Guangdong Provincial People′s Hospital from May 2021 to September 2022 were prospectively included. Age and gender matched healthy volunteers (control group) were included during the same period. Both the control group and HOCM patients underwent CMR examination (including cine sequence and 4D Flow sequence) before and 6 months after surgery. CMR 4D flow technology was used to evaluate changes in AAo preoperative and postoperative blood flow patterns (eddy currents, spiral flow), maximum energy loss (EL max), and average energy loss (EL avg). HOCM patients underwent laboratory tests, including N-terminal pro-brain natriuretic peptide (N-pro BNP) and high-sensitivity troponin T (hsTnT). At the same time, the correlation between postoperative energy loss in HOCM patients and the degree of improvement in laboratory biomarkers was explored. Results:A total of 15 HOCM patients and 15 healthy volunteers were included. (1) In terms of blood flow patterns, the preoperative spiral flow degree of HOCM patients was significantly higher than that of the control group ( P=0.001), but the postoperative difference was not statistically significant ( P=0.059). The degree of eddy currents in HOCM patients before and after surgery was higher than that in the control group (all P<0.05). (2) In terms of energy loss, the preoperative EL max [21.17(14.30-28.10)mW vs 10.17(7.66-13.07)mW, P<0.001] and EL avg [4.87(3.46-5.77)mW vs 2.27(2.19-2.27)mW, P=0.023] of HOCM patients were higher than those of the control group, but there was no statistically significant difference between the postoperative and control groups (all P>0.05). Compared with preoperative, the postoperative EL max [12.33(8.70-17.41)mW] and EL avg [3.10(2.25-4.40)mW] of AAo in HOCM patients were significantly reduced (mean P=0.001). (3) Correlation analysis showed that there was a positive correlation ( r=0.587, P=0.021) between the EL max of AAo and the degree of improvement in hsTNT after interventricular septum myocardial resection, but no significant correlation ( r=0.229, P=0.413) with the degree of improvement in NT-pro BNP. Conclusions:The degree of postoperative AAo blood flow disorder in HOCM patients is reduced, and EL max and EL avg are significantly reduced. The EL max of postoperative AAo is positively correlated with the degree of improvement in hsTNT, suggesting that EL max may be applicable for prognostic evaluation of patients.

ObjectiveTo discuss the diagnostic methods of global developmental delay caused by 10q24.3 heterozygous loss. MethodsA retrospective analysis was conducted on the clinical data of one child with global developmental delay， and the results of low depth whole-genome copy number variation sequencing （CNVseq） and family whole exome sequencing （WES） of the child and his parents. ResultsThe patient was a 10-month-old male with developmental retardation in four areas， with some special features （ocular hypertelorism， strabismus， flat nose bridge， protruding forehead， cleft palate， high palatal arch， etc.） and hypotonia of limbs. The CNVseq and WES test showed that the patient had new 10q24.3 heterozygosis loss. Because this region contains the gene SUFU associated with basal cell nevus syndrome and the gene CNNM2 associated with hypomagnesemia， seizures， and mental retardation， and the gene TRIM8 associated of Focal segmental glomerulosclerosis with neurodevelopmental syndrome， we speculated that the cause of the disease in the child was highly related to the heterozygosity deletion of SUFU gene and CNNM2 gene and TRIM8 gene. ConclusionGenetic testing should be improved as soon as possible for children with global developmental delay and special facial manifestations， so as to make clear diagnosis and to judge prognosis.

Objective To explore the value of prophylactic anticoagulation in the 28-day prognosis of patients with severe COVID-19.Methods The clinical data of COVID-19 patients admitted to Guangdong Provincial People's Hospital from December 2022 to January 2023 were collected,including age,gender,past medical history,routine blood test,liver and renal function,procalcitonin,coagulation function,Padua prediction score,antiviral therapy,hormonotherapy,immunotherapy and anticoagulation therapy.The patients were divided into an anticoagula-tion group and a non-anticoagulation group.The differences in various indicators were compared between the two groups.Cox regression was performed to assess the independent risk factors for 28-day mortality and the anticoagula-tion efficacy between the subgroups.Results Among 158 patients,128 received anticoagulation;There were significant differences between the two groups in case number of hypertension and critical condition,lymphocyte count,prothrombin time,D-dimer,and case number of immunotherapy.COX logistic regression showed that antico-agulation(HR = 2.25,95%CI:1.01～5.01,P = 0.048)was an independent risk factor for all-cause mortality of COVID-19 patients within 28 days.Subgroup analysis showed that anticoagulation therapy led to an increase in the 28-day mortality as level of procalcitonin of≥0.5 pg/mL(HR = 2.72,95%CI:1.05～7.04)or D-dimer of<2 000 ng/mL(HR = 9.16,95%CI:1.63～51.48).Conclusions Prophylactic anticoagulation did not reduce all-cause mortality of COVID-19 within 28 days.

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.
China ; Clinical Trials as Topic ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional ; Nonprescription Drugs/therapeutic use* ; Quality of Life ; Reproducibility of Results

Objective:To investigate the clinical effect of free fibula flap transplantation in repairing the defect of mandibular osteoradionecrosis (ORN).Methods:A total of 151 mandibular ORN patients undergoing free fibular flap transplantation were selected from August 2005 to September 2020 in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among them, 109 patients were males and 42 patients were females, aged (54.1±10.1) (ranged 31-85) years old. The clinical data of the patients was collected and the survival rate of the flaps and postoperative function were calculated to evaluate the surgical efficacy. The χ 2 test was used for difference analysis. Results:Among the 151 patients, mandibular ORN caused by radiotherapy for nasopharyngeal carcinoma accounted for 79.5% (120/151). The average time for mandibular ORN appeared was 5(6) years after radiotherapy. Facial artery [57.2%(87/152)] and superior thyroid artery [32.9%(50/152)] were the main anastomotic arteries in the recipient area. There was no significant difference in the necrosis rates of the two flaps [10.3%(9/87) and 12.5% (5/50), respectively, P=0.949]. The main anastomotic veins in the recipient area were the external jugular vein [48.4%(135/279)] and the common facial vein [26.5%(74/279)]. Twenty-five cases (16.6%) had one vein anastomosed, and 126 cases (83.44%) had two veins anastomosed. There was no significant difference in the flap necrosis rate between the two conditions [20.0%(5/25) and 7.1%(9/126), respectively, P=0.100]. Ninety-seven cases (64.2%) used the peroneal musculocutaneous-fascia composite flap to repair the maxillofacial soft and hard tissue defects. Thirteen cases (8.6%) underwent the restorations with digital virtual surgery design, of which 5 cases were repaired with dental implants at the same time. After the operations, lower respiratory tract infection occurred in 17 patients (11.3%), and upper respiratory tract obstruction occurred in 3 cases (2.0%). The survival rate of the flap after operation was 90.7% (136/151), and 21 patients (13.9%) had flap vascular crisis. Delayed healing of maxillofacial wounds occurred in 33 cases (21.9%). After 3 to 24 months of follow-ups, 110 patients (76.9%) had no fistula inside/outside the oral cavity, 118 patients (82.5%) had an improvement in opening mouth of increasing (≥0.5 cm) after surgery, 135 patients (94.4%) had pain relief, 97 cases (67.8%) could eat normal diet, semi-liquid or soft food, and 137 cases (95.8%) were satisfied or basically satisfied with the treatment effects. Conclusions:The free fibular flap transplantation is an effective method to repair mandibular ORN defects. Preoperative vascular assessment is helpful for the selection of recipient vessels. Facial artery, superior thyroid artery, external jugular vein and common facial vein can be used as the main recipient vessels. The repair of the peroneal musculocutaneous-fascia composite flap facilitates the closure of internal and external fistulas. Digital technology can help to restore the maxillofacial shape more accurately, improve the patient′s occlusal and chewing function and enhance the quality of life of mandibular ORN patients.

Objective:To evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) and arbidol in treating patients with coronavirus disease 2019 (COVID-19) in the real world.Methods:The clinical data of 178 patients diagnosed with COVID-19 admitted to Guangzhou Eighth People′s Hospital from January 20 to February 10, 2020 were retrospectively analyzed. According to patient′s antiviral treatment regimens, 178 patients were divided into 4 groups including LPV/r group (59 patients), arbidol group (36 patients), LPV/r plus arbidol combination group (25 patients) and the supportive care group without any antiviral treatment (58 patients). The primary end point was the negative conversion time of nucleic acid of 2019 novel coronavirus (2019-nCoV) by pharyngeal swab.Results:The baseline parameters of 4 groups before treatment was comparable. The negative conversion time of viral nucleic acid was (10.20±3.49), (10.11±4.68), (10.86±4.74), (8.44±3.51) days in LPV/r group, arbidol group, combination group, and supportive care group respectively ( F=2.556, P=0.058). There was also no significant difference in negative conversion rate of 2019-nCoV nucleic acid, the improvement of clinical symptoms, and the improvement of pulmonary infections by CT scan ( P>0.05). However, a statistically significant difference was found in the changing rates from mild/moderate to severe/critical type at day 7 (χ 2=9.311, P=0.017), which were 24%(6/25) in combination group, 16.7%(6/36) in arbidol group, 5.4%(3/56) in LPV/r group and 5.2%(3/58) in supportive care group. Moreover, the incidence of adverse reactions in three antiviral groups was significantly higher than that in supportive care group (χ 2=14.875, P=0.002). Conclusions:Antiviral treatment including LPV/r or arbidol or combination does not shorten the negative conversion time of 2019-nCoV nucleic acid nor improve clinical symptoms. Moreover, these antiviral drugs cause more adverse reactions which should be paid careful attention during the treatment.

Objective:To investigate the difference of HRCT imaging features between COVID-19 and the ground-glass opacity(GGO) lesion of early-stage lung carcinoma, standardize the diagnosis and treatment process of ground-glass opacity(GGO) degeneration during the epidemic.Methods:A total of 34 patients with diagnosed COVID-19 who confirmed by positive results of the new coronavirus nucleic acid test were collected as observation group 40 patients with pathologically diagnosed early-stage lung carcinoma whose preoperative HRCT examination showed pure ground glass lesions and received surgical intervention were recruited from the Department of Thoracic Surgery (The First Affiliated Hospital of Xiamen University) from January 2018 to December 2019 as the control group. The HRCT imaging features of these two groups of patients were compared and statistically analyzed.Results:The HRCT imaging features of the new type of COVID-19 showed significant difference by characteristics of multiple lesions, lesion rapid variation within 3 days, reticular pattern, vacuolar sign and clear boundary compared to the GGO lesion of early-stage lung carcinoma( P<0.05). The chinical and imaging characteristic the sex, age, with pleural effusion or not and the lesion location showed no significant difference between these 2 groups ( P>0.05). Conclusion:Contrast with inert early lung carcinoma lesions, COVID-19 disease developed rapidly. Imaging dynamic examination can provide evidences to distinguish Novel Coronavirus Pneumonia and early-stage lung carcinoma.

OBJECTIVETo screen the differentially expressed miRNAs and their target genes in adipogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) to better understand the mechanism for regulating the balance between osteoblast and adipocyte differentiation.

METHODSCultured hMSCs were induced for adipogenic differentiation, and at 0, 7, 14, and 21 days of induction, the cells were examined for miRNA and mRNA expression profiles using miRNA chip and transcriptome sequencing (RNA-seq) techniques. Correlation analysis was carried out for the miRNAs and mRNAs of potential interest. The databases including TargetScan, PicTar and miRanda were used to predict the target genes of the differentially expressed miRNA.

RESULTSThe expression of miR-140-5p was down-regulated and leukemia inhibitory factor receptor (LIFR) expression increased progressively during adipogenic differentiation of hMSCs, showing a negative correlation between them. Target gene prediction using the 3 databases identified LIFR as the target gene of miR-140-5p.

CONCLUSIONmiRNA-140-5p may play an important role by regulating its target gene LIFR during adipogenic differentiation of hMSCs.

Adipocytes ; cytology ; Adipogenesis ; Cell Differentiation ; Cells, Cultured ; Down-Regulation ; Humans ; Leukemia Inhibitory Factor Receptor alpha Subunit ; metabolism ; Mesenchymal Stromal Cells ; cytology ; MicroRNAs ; genetics ; Oligonucleotide Array Sequence Analysis ; Osteoblasts ; cytology ; RNA, Messenger ; Transcriptome