BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

Objective To investigate the effect of Osteoporosis Self-Assessment Tool for Asia(OSTA)index on brachial ankle pulse wave velocity(baPWV)and its predictive value for peripheral atherosclerosis in menopausal women.Methods A total of 1 138 menopausal women who underwent physical examination at our hospital from January 2022 to December 2022 were enrolled in the study.General clinical data were collected,the OSTA index was calculated,and baPWV was measured.Patients were divided into the control group(n=539)and the peripheral atherosclerosis group(n=599)according to the baPWV values(peripheral atherosclerosis occurs with baPWV≥1 400 cm/s).Linear regression and Logistic regression were used to analyze the effect of OSTA index on baPWV in menopausal women.The predictive value of peripheral atherosclerosis was evaluated using the receiver operating characteristic(ROC)curve.Results The OSTA index was lower in the peripheral atherosclerosis group than that in the control group[-0.40(-2.20,1.00)vs.0.40(-0.60,1.40),P＜0.05].Univariate linear regression analysis was used to conclude that the OSTA index was an influencing factor of baPWV,and after correcting for risk factors,multivariate linear regression analysis indicated that OSTA index still affected the value of baPWV(P＜0.05).The linear regression equation was baPWV=-27.911-39.752×OSTA+6.444×SBP+7.008×DBP+11.506×HCY+27.942×Hs-CRP.Logistic regression analysis suggested that increased OSTA index was a protective factor for peripheral atherosclerosis(OR=0.664,95%CI:0.535-0.823,P＜0.001).ROC curve analysis suggested that OSTA index was-1.25 as the optimal cutoff point,which predicted peripheral atherosclerosis with an area under the curve of 0.619,a sensitivity of 36.2%and a specificity of 86.3%.Conclusion In menopausal women,OSTA index is an influential factor for baPWV,and increased OSTA index is a protective factor against peripheral atherosclerosis,which can be used to predict baPWV value.

Objective:To investigate the clinical application effects of combination of different types of free perforator flaps in the repair of complex wounds in extremities.Methods:A retrospective observational study was conducted. From January 2018 to June 2022, 11 patients with complex wounds in extremities who met the inclusion criteria was admitted to the Affiliated Hospital of Zunyi Medical University, including 8 males and 3 females, aged 28 to 55 years. The wounds in the upper extremities in 4 cases and in the lower extremities in 7 cases were repaired with different combination of free perforator flaps. After debridement, the wound area was 7.0 cm×6.0 cm-28.0 cm×12.0 cm. A combination of different types of perforator flaps were applied, including the perforator tri-leaf flap of the descending branch of the lateral femoral circumflex artery in 6 cases, the descending branch of lateral femoral circumflex artery combined with oblique branch perforating branch flap in 2 cases, the lobulated flap of the descending branch of the lateral femoral circumflex artery combined with the contralateral medial plantar artery perforator flap in 2 cases, and the bilateral perforator flap of the descending branch of lateral femoral circumflex artery combined with great toe nail flap in 1 case, with the size of a single flap ranged from 2.0 cm×2.0 cm-25.0 cm×6.0 cm. The donor site was repaired by direct suture, skin grafting, or flap transplantation. During free flap transplantation, the flap was cut and split according to the distribution of perforators, and end-to-end or end-to-side anastomosis was performed between the donor area and the recipient area. After surgery, the survival of transplanted flap in the primary recipient site, the occurrence of vascular crisis, the wound healing in the flap donor site, and the survival of transplanted skin or flap in the flap donor site were observed. During follow-up, the blood supply, appearance and texture of the transplanted flap in the primary recipient site were observed; and at the same time, the weight bearing of the plantar receiving area, the presence of sliding, ulcers, and sinus tracts of the flap, and the appearance and function of the hand were observed; the complications in the donor area were observed.Results:After surgery, one patient's transplanted flap in the primary recipient site had vascular crisis but survived after exploration+vein graft bridging; partial necrosis occurred in one lobe of anterolateral thigh lobulated flap transplanted to the primary recipient site in one patient and recovered after dressing change+skin grafting, and the different types of perforator flap transplanted to the primary recipient site in the other 9 patients all survived. After surgery, the wound with direct suture at the donor site healed well, and the skin or flap transplanted to the donor area survived well. During 3-24 months of follow-up, the blood supply, appearance, and texture of the transplanted flap at the primary recipient site were good. In two patients, the anterolateral thigh flap combined with the medial plantar flap were used to repair plantar defects. The plantar receiving area was able to bear weight, and the texture of the flaps in the recipient area was close to the normal plantar skin, without flap sliding, ulcer, or sinus tract formation. In one patient, bilateral anterolateral thigh flap combined with great toe nail flap were used to repair hand combined with soft forearm defect, and the appearance and function of hand, especially thumb were good. Only linear scar was left in the donor site without other obvious complications.Conclusions:The combination of different types of perforator flaps is a reliable clinical method to repair complex wounds in extremities with high safety, good efficacy, and less complications.

OBJECTIVE To evaluate the efficacy， safety and economical efficiency of Xuesaitong injection in the treatment of stroke by rapid health technology assessment，so as to provide evidence for clinical rational drug use. METHODS Retrieved from Wanfang database， CBM， CNKI，PubMed，Cochrane Library，Embase， INAHTA and HTAI databases or organization websites， health technology assessment （HTA） reports， meta-analysis/systematic reviews and pharmacoeconomic studies related to Xuesaitong injection in the treatment of stroke were summarized and analyzed. RESULTS A total of 29 pieces of literature were included. Among them， 14 studies were conducted on meta-analysis/systematic reviews，15 studies were conducted on pharmacoeconomics， HTA was not obtained. The results of meta-analysis/systematic reviews showed that Xuesaitong injection had certain advantages for stroke in improving the total effective rate， clinical symptoms and related scale scores compared with blank control group and some drug control groups. Safety studies had shown that the adverse reactions of Xuesaitong injection were mainly allergic-like reactions. The results of pharmacoeconomic evaluation are quite different， which may also be related to the long time span among various studies and the adjustment of some drug prices. CONCLUSIONS Xuesaitong injection in the treatment of stroke is helpful to improve the clinical efficacy and evaluation indexes， but there are some serious adverse reactions， and it is not economically superior to some chemical drugs.

Objective:To evaluate the effect of metformin on ultraviolet A (UVA) -induced photoaging of an immortalized human keratinocytes cell line (HaCaT), and to explore its potential mechanisms.Methods:Cell counting kit 8 (CCK8) assay was performed to evaluate the effect of metformin at different concentrations (0 - 100 mmol/L) on the viability of HaCaT cells, and 10 mmol/L metformin was selected for subsequent experiments. Cultured HaCaT cells were divided into a blank control group (conventional culture), a metformin group (treated with culture medium containing 10 mmol/L metformin), a UVA irradiation group (conventional culture for 24 hours followed by 10 J/cm 2 UVA irradiation) and a metformin + UVA group (treated with culture medium containing 10 mmol/L metformin for 24 hours followed by 10 J/cm 2 UVA irradiation) ; UVA irradiation was performed at a dose of 10 J/cm 2 once a day for 3 consecutive days. After 4-day treatment, cells were collected, the β-galactosidase assay was performed to determine the proportion of senescent cells in each group, 2′, 7′-dichlorodihydrofluorescein diacetate assay to detect levels of intracellular reactive oxygen species (ROS), and the comet assay to detect DNA damage levels. Additionally, some HaCaT cells were divided into the blank control group, metformin group, 1.25 μmol/L dorsomorphin (an adenosine monophosphate-activated protein kinase [AMPK] inhibitor) + metformin group, and 2.5 μmol/L dorsomorphin + metformin group, and cells in the latter two groups were treated with 1.25 and 2.5 μmol/L dorsomorphin respectively for 2 hours, followed by the treatment with 10 mmol/L metformin for 24 hours. Western blot analysis was performed to determine the cellular localization and phosphorylation levels of nuclear factor-erythroid 2-related factor 2 (Nrf2). By using the small-interfering RNA (siRNA) -mediated silencing method, siRNA-Nrf2 was transfected into HaCaT cells to knock down Nrf2 expression (siRNA-Nrf2 group) ; 2.5 μmol/L dorsomorphin-treated HaCaT cells or Nrf2-knockdown HaCaT cells were treated with metformin and UVA irradiation (dorsomorphin + metformin + UVA group, siRNA-Nrf2 + metformin + UVA group, respectively), and the proportions of senescent cells were further calculated in each group. Statistical analysis was carried out by using one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Treatment with different concentrations of metformin for 24 hours could affect the viability of HaCaT cells to varying degrees ( F = 5 206.31, P < 0.001) ; there were no significant differences in the relative survival rates of HaCaT cells between the 10 - 20 mmol/L metformin groups and the control group (0 mmol/L metformin group, all P > 0.05), while the relative cell survival rates were significantly lower in the 25 - 100 mmol/L metformin groups than in the control group (all P < 0.05). After UVA irradiation, HaCaT cells shrank significantly and became narrow and elongated, and the intercellular spaces increased; the relative cell survival rate was significantly lower in the UVA irradiation group (76.13% ± 1.03%) than in the blank control group (100.00% ± 1.24%, LSD- t = 14.86, P < 0.001), but significantly higher in the metformin + UVA group (106.69% ± 2.45%) than in the UVA irradiation group (LSD- t = 11.55, P < 0.001). Moreover, the UVA irradiation group showed significantly increased proportions of senescent cells (45.14% ± 4.98%), intracellular ROS levels (144.61% ± 4.91%), and percentages of DNA in the tail (75.33% ± 1.77%) compared with the blank control group (23.84% ± 1.89%, 55.49% ± 1.57%, 1.88% ± 0.29%, respectively, all P < 0.001), while the metformin + UVA group showed significantly decreased proportions of senescent cells (24.26% ± 1.34%), intracellular ROS levels (58.62% ± 2.17%), percentages of DNA in the tail (15.83% ± 1.23%) compared with the UVA irradiation group (all P < 0.001). Western blot analysis showed that the Nrf2 expression in the cytoplasm was lower in the 10 mmol/L metformin group than in the blank control group, while the phosphorylated Nrf2 expression in the nuclei was higher in the 10 mmol/L metformin group than in the blank control group, suggesting that metformin could effectively induce the phosphorylation of Nrf2 and its nuclear translocation; both the pretreatment with 1.25 and 2.5 μmol/L dorsomorphin could significantly reduce the phosphorylation levels of AMPKα and Nrf2 induced by 10 mmol/L metformin. The proportions of senescent cells in the dorsomorphin + metformin + UVA group and the siRNA-Nrf2 + metformin + UVA group were 67.84% ± 2.74% and 65.94% ± 1.33%, respectively, which were significantly higher than those in the metformin + UVA group (37.76% ± 1.64%, t = 14.45, 13.34, respectively, both P < 0.001) . Conclusion:Metformin may inhibit UVA-induced photoaging of HaCaT cells by activating the AMPK/Nrf2 signaling pathway, scavenging ROS and reducing DNA damage.

Objective:To investigate high resolution CT (HRCT) manifestations and clinical features of patients infected with the novel coronavirus B.1.617.2 variant.Methods:A total of 125 patients with the novel coronavirus B.1.617.2 variant in Guangzhou Eighth People′s Hospital from May 21 to June 9, 2021 was enrolled. There were 52 males and 73 females, aged from 1 to 92 years old with a median age of 47 year. The clinical features and HRCT characteristics were analyzed retrospectively.Results:Of the 125 patients, the main clinical manifestations were fever in 54 patients, cough in 50 patients, pharyngeal discomfort in 39 patients, and diarrhea in 5 patients. HRCT showed pneumonia in 96 cases, which predominantly had ground-glass opacities in 92 cases, ground-glass opacities combined with local consolidation in 22 cases, consolidation in 11 cases, intralobular interstitial thickening in 51 cases, centrilobular structural thickening in 23 cases, and cord-like lesions in 33 cases. One patient had pleural effusion, and no enlarged lymph nodes were observed in all patients. The lesions were distributed in the subpleural and/or peripheral lung in 96 cases and along the bronchovascular bundle (middle and inner zone) in 24 cases. The time interval from onset to positive HRCT was 3 (1, 4) days in 96 patients with pneumonia on HRCT. HRCT showed absorption after the imaging findings reaching the peak in 20 patients, and the time interval between the first positive HRCT findings and the peak imaging was 6 (3, 7) days in these 20 patients.Conclusions:The novel coronavirus B.1.617.2 variant has a strong infectivity, short viral latency. Lung injury is decreaseel. People of all ages are susceptible and the diseasemay have rapid pnegression. HRCT mainly shows ground glass opacities, which are more common in subpleural and/or in the lung periphery, with interlobular thickening.

OBJECTIVE: To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography. METHODS: Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein. CONCLUSION The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.
Female ; Fetus ; Humans ; Mandibulofacial Dysostosis/genetics* ; Mutation ; Peptide Elongation Factors/genetics* ; Phenotype ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/genetics*

Objective:Aanalysis the effect of booster one dose of hepatitis B vaccine after 21-32 years of primary immunization in Zhengding Country of Hebei Province.Methods:A total of 322 participants who were born between 1986 and 1996, received a full course of primary vaccination with plasma-derived hepatitis B vaccine (HepB), had no experience with booster vaccination, were HBsAg, anti-HBcnegative, had anti-HBs<10 mIU/ml, completed the booster and had laboratory results were enrolled between August 2017 to February 2018. A simple random method was uesd to randomly assigned 322 subjects to two groups, receiving a booster dose of HepB derived from either Saccharomyces cerevisiae ［HepB (SC), (151 cases)］ or Chinese hamster ovary-derived HepB ［HepB (CHO), (171 cases)］, the dose was 20 μg. Blood samples were collected 30 days after boosting and quantitatively tested for the geometric mean concentration (GMC) of anti-HBs to assess immunological effect. The related influencing factors of GMC and seroconversion rates of anti-HBs were analyzed by multiple linear regression and multivariate logistic regression models.Results:The 266 subjects (82.61%) had anti-HBs≥ 10 mIU/ml, and GMC was (131.63±12.94) mIU/ml.The seroconversion rates of anti-HBs in the anti-HBs<2.5 mIU/ml group and 2.5-10 mIU/ml group were 74.54% (161 cases) and 99.06% (105 cases), respectively ( P<0.001).The seroconversion rates of anti-HBs after one dose of HepB (CHO) was higher than that of one dose of HepB (SC), the seroconversion rates were 87.13% (149 cases) and 77.48% (117 cases), respectively ( P=0.023). Participants boostered with HepB (CHO) was the factor influencing the effect of strengthening immunization compared with boostered with HepB (SC), and OR (95% CI) was 1.91 (1.02-3.56) ( P=0.042).Compared with anti-HBs<2.5 mIU/ml, prebooster anti-HBs was between 2.5 mIU/ml and 10 mIU/ml was the related factor of seroconversion rates of anti-HBs after booster immunization, and OR (95% CI) was 36.15 (4.91-266.02) ( P<0.001). Conclusion:Participants boostered withone dose of HepB had a good immune response. Pre-booster anti-HBs concentration and a variety of vaccine were related factors of immune response.

With the popularity of cataract and refractive surgery, especially the increasing implantation of advanced technology lens implants, dry eye significantly affects image quality.In 2017, the Asia-Pacific Association of Cataract and Refractive Surgeons (APACRS) produced the new Principles of Preferred Practice for the Management of the Ocular Surface in Cataract and Refractive surgery (hereafter referred to as the PPP). This document provides detailed evidence-based discussions on the incidence rate, pathogenesis, diagnosis, evaluation, clinical symptoms, and treatment of dry eyes during perioperative period of refractive surgery and cataract surgery.The article which interpreted the PPP is aimed to remind general ophthalmologists to pay more attention to the dry eye in cataract and refractive surgery, and make the management of the ocular surface more standardized.