Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Primary liver cancer(PLC)is a common malignant tumor in China.It ranks second in the cause of tumor mortality and it is a serious threat to the lives and health of people.Transcatheter arterial chemoembolization(TACE)is the preferred treatment for patients with HCC who cannot be surgically cured,which is of great significance for prolonging the patient's life.However,the incidence of nausea and vomiting after TACE is very high,which is an important reason for the decline of patient treatment compliance,which seriously affects the quality of life and the effect of interventional therapy.This paper reviews the domestic and abroad literature concerning the nausea and vomiting in patients after TACE,focusing on the clinical features of nausea and vomiting,the risk factors and the assessment tools,so as to provide a scientific basis for clinical early identification and effective intervention of nausea and vomiting after TACE.(J Intervent Radiol,2024,33:565-570)

Objective: To explore the preoperative whole perforator evaluation and intraoperative eccentric design of anterolateral thigh flap (ALTF) based on superficial fascial perforators by modified computed tomography angiography (CTA), and the clinical effects were observed. Methods: A prospective observational study was adopted. Twelve patients with oral and maxillofacial tumors and 10 patients with open injury of the upper limb with large soft tissue defects were hospitalized in the Department of Hand & Microsurgery and Department of Oral & Maxillofacial Surgery of Affiliated Hospital of Binzhou Medical University from January 2021 to July 2022, with 12 males and 10 females, aged from 33 to 75 years, an average age of 56.6 years. The wounds of the patients with oral and maxillofacial tumors were reconstructed by ALTF after the extensive tumor resection and radical cervical lymph node dissection in the same stage; the wounds of the patients with skin and soft tissue defect on the upper limb were covered by ALTF in stage Ⅱ after debridement in stage Ⅰ. After debridement, the area of wound was 3.5 cm×3.5 cm-25.0 cm×10.0 cm and the area of the required flap area was 4.0 cm×4.0 cm-23.0 cm×13.0 cm. Modified CTA scan was performed on the donor site of ALTF before the operation, with the parameters of modified CTA being set to mainly reduce the tube voltage and tube current, and increase the contrast dose and the dual phase scan. The acquired image data were sent to GE AW 4.7 workstation and adopted the volume reconstruction function for visual reconstruction and evaluation of the whole perforator. The information of perforator and source artery was marked on the body surface before operation according to the above evaluation. During the operation, an eccentric flap centered on the visible superficial fascia whole perforator was designed and cut according to the desired flap area and shape. The donor sites of the flap were repaired by direct sutures or full-thickness skin grafts. The total radiation dose was compared between the modified CTA scan and the traditional CTA scan. The distribution of outlet point of perforator of double thighs, the length and direction of superficial fascia perforators based modified CTA were recorded. The type, number, and origin of the target perforator, distribution of of outlet point of perforator, and the diameter, course, and branch of the source artery observed before the operation were compared with those observed during the operation. The healing of donor site wound and the survival of flaps in recipient site were observed after operation. The texture and appearance of flap, oral and upper limb functions, and the functions of femoral donor sites were followed up. Results: The total radiation dose of modified CTA scan was lower than that of the traditional CTA scan. A total of 48 perforators of double thighs were observed, among which, 31 (64.6%) perforators went outward and downward, 9 (18.8%) perforators went inward and downward, 6 (12.5%) perforators went outward and upward, and 2 (4.2%) perforators went inward and upward, and the average length of superficial fascia perforators was 19.94 mm. The preoperative observed type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery were basically consistent with the intraoperative exploration. The types of 15 septocutaneous (including musculoseptocutaneous) perforators and 10 musculocutaneous perforators observed before the operation was consistent with intraoperative exploration. The distance between the mark of the surface perforator point and the actual exit point of the perforator during operation was (0.38±0.11) mm. All flaps survived without vascular crisis. The donor site wounds of 5 cases of skin grafting and 17 cases of direct suturing wounds healed well. The postoperative follow-up was 2 months to 1 year, with an average of 8.2 months, the flaps were soft and slightly bloated; the function of diet and mouth closing was accessible in patients with oral and maxillofacial tumors, the speech function was mildly impaired in patients with tongue cancer, but they could complete basic oral communication; the wrist and elbow joints and forearm rotation function were not significantly limited in patients with upper limb soft tissue injuries; there was no obvious tightness in the donor sites, and the function of the hip and knee joints was not limited. Conclusions: The whole perforator and even the subcutaneous perforator of the donor site of ALTF can be evaluated by modified CTA, and the flap can be used in oral or maxillofacial reconstruction and repair of skin and soft tissue defects of upper limbs to achieve good results. By clarifying the type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery before the operation, the eccentric design of the ALTF based on the superficial fascia perforator was realized. This study has strong guiding value.
Female ; Male ; Humans ; Middle Aged ; Adult ; Aged ; Thigh ; Computed Tomography Angiography ; Prospective Studies ; Subcutaneous Tissue ; Tomography, X-Ray Computed

Age-related ovarian hypofunction includes a decrease in follicle quantity and quality as well as alterations in the ovarian microenvironment，the mechanisms of which are mainly related to mitochondrial dysfunction，free radical and antioxidant systems，telomere and telomerase alterations，and apoptosis，and is one of the major factors contributing to infertility in advanced maternal age （AMA）. Despite the tremendous progress in assisted reproductive technology in recent decades，few breakthroughs have been made in alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA. In recent years，there has been an increasing number of studies on the multi-level and multi-targeted mechanisms of traditional Chinese medicine （TCM） to improve age-related ovarian hypofunction by modulating mitochondrial homeostasis，alleviating oxidative stress，and inhibiting apoptosis，while more high-quality randomized controlled trials have demonstrated the clinical efficacy of TCM in assisted reproductive technology. Given this，this article presented a systematic review of recent research and randomized controlled trials on the mechanism of Chinese medicine active ingredients，single Chinese medicine， and Chinese medicine compounds in delaying age-related ovarian hypofunction，to clarify the current status and shortcomings of the research. This paper provides medication management of TCM for effectively alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA.

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.

Objective: To investigate the effects of glycogen synthase kinase-3β (GSK3β)/eukaryotic extension factor kinase 2 (eEF2K) signaling pathway on the process of pulmonary fibrosis through in vivo experiments, and find new ideas for clinical treatment of pulmonary fibrosis. Methods: The pulmonary fibrosis model of C57BL/6 male mice was induced by bleomycin with intratracheal injection at the dose of 2 mg/kg. After 14 days of modeling, animals were divided into model group, negative inhibition group and inhibition group (n=5 for each group), and control group was not processed. The inhibition group was treated with TDZD-8 (4 mg/kg) after modeling, the negative inhibition group was given DMSO solution after modeling, and the samples were collected after 28 days. Hematoxylin-eosin staining method was used to detect lung fibrosis in mice and scored according to Ashcroft scale. Expression levels of GSK3β, p-GSK3β, eEF2K, p-eEF2K (Ser70, Ser392, Ser470), precursor protein of matrix metalloproteinase-2 (pro-MMP-2), matrix metalloproteinase-2 (MMP-2), collagen I (Col I), collagen Ⅲ (Col Ⅲ) and α-smooth muscle actin (α-SMA) were detected by Western blot. Results: Compared with control group, the fibrosis score was up-regulated, the expression levels of GSK3β, p-GSK3β, p-eEF2K (Ser70, Ser392, Ser470), pro-MMP-2, MMP-2, Col I, Col Ⅲ and α-SMA were increased, while that of eEF2K was decreased in model group (P＜0.05). Compared with model group, the fibrosis score, expression levels of GSK3β, p-GSK3β, p-eEF2K (Ser70, Ser392, Ser470), pro-MMP-2, MMP-2, Col I, Col Ⅲ and α-SMA were decreased, but the expression level of eEF2K was increased in inhibition group (P＜0.05). Conclusion: GSK3β can activate eEF2K by phosphorylation at the sites of Ser70, Ser392 and Ser470, increase the contents of fibrosis indicators, promote the formation of pulmonary fibrosis, and aggravate lung tissue lesions.
Animals ; Collagen ; Collagen Type I ; Elongation Factor 2 Kinase/metabolism* ; Eukaryota/metabolism* ; Fibrosis ; Glycogen Synthase Kinase 3 beta ; Male ; Matrix Metalloproteinase 2/metabolism* ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis/chemically induced* ; Signal Transduction

OBJECTIVE: To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors. METHODS: The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method. RESULTS: Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P>0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P<0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543). CONCLUSION Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.
Acute Disease ; Child ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Retrospective Studies ; Risk Factors ; Tissue Donors