Volume 97  ·  Issue 19  ·  2017

In order to adapt to the legal spirit of the General Principles of Civil Law of the People's Republic of China, the Law of the People's Republic of China on Practicing Physicians adopted by the Third Session of the Standing Committee of the Ninth National People's Congress on June 26, 1998, the Regulations on the Administration of Medical Institutions promulgated by the State Council on February 26, 1994, as well as administrative regulations and departmental rules, the Detailed Rules for the Implementation of the Regulations on the Administration of Medical Institutions, the Basic Standards of Medical Institutions (for Trial Implementation) and the Interim Provisions on the Scope of Practice in the Registration of Physicians, the medical technology management reform has been carried out at the national level, especially in order to implement the requirements of the reform of the administrative examination and approval system of the State Council, according to the Decision of the State Council on Cancelling Non-administrative License Examination and Approval Matters (Guofa [2015] No.27), the National Health and Family Planning Commission has decided to cancel the examination and approval of the third type of clinical application of medical technology. "Medical Technology with Restricted Clinical Application (2015 Edition)" is clearly put forward, with the purpose of strengthening the work measures of interim and post-event supervision after the non-administrative licensing approval of restricted medical technology, so as to ensure medical quality and patient safety.

Organized by the Medical Quality Division of the Medical Administration and Hospital Administration Bureau of the National Health and Family Planning Commission, sponsored by the Radioactive Particle Therapy Technology Expert Committee of Chinese Medical Doctors Association and the Particle Therapy Branch of the Minimally Invasive Cancer Therapy Professional Committee of China Anti-Cancer Association, and hosted by Zhongda Hospital affiliated to Southeast University, the Forum of the Radioactive Particle Implantation Therapy Technology Expert Committee was held in Nanjing in December 2016. The theme of this forum is: Dose and Quality, Technology and Quality. After the discussion at the meeting, a number of new views and ideas were produced, the current industry problems of radioactive particle therapy were pointed out, and the future development direction of the industry was put forward.

In recent years, Western countries such as the United States and the United Kingdom have successively launched national-level precision medicine research, and my country also launched a precision medicine program in 2016^[1]。 precision medicine is a medical model that fully considers the individual differences of patients in genes, environment and lifestyle to achieve the most effective disease treatment and prevention. Its core concept is to synthesize multi-dimensional data related to human health and disease prevention, and on this basis, treat and prevent diseases, improve population health, avoid excessive medical treatment, and better allocate medical resources. The focus of precision medicine research is to explore and interpret the pathogenesis of diseases with the help of new biological technologies and IT technologies, explore the differences in genes, environment and lifestyle of sick individuals to the greatest extent, complete deep integration with clinical data, and establish a knowledge system through advanced technologies such as artificial intelligence, predictive models and machine learning, so as to put forward new concepts, methods and schemes for the treatment and prevention of diseases^[2]。 In March 2016, precision medicine was officially included in the 13th Five-Year Plan and became one of the strategic directions for China's future medical development.

This specification is formulated in order to standardize the clinical application of radioactive particle implantation therapy technology and ensure medical quality and medical safety. This specification is the minimum requirement for medical institutions and their medical staff to carry out radioactive particle implantation therapy technology. The term "radioactive particle implantation therapy technology" mentioned in this specification refers to the radioactive particle implantation therapy technology of malignant tumors, and the application scope covered includes: radioactive particle implantation under the guidance of percutaneous imaging (ultrasound, CT, MRI, etc.) of solid tumors, endoscopic (including laparoscopy, thoracoscopy, natural tube endoscopy, etc.) radioactive particle implantation, cavity organ particle stent implantation, and radioactive particle implantation under direct surgical vision.

Members of the Expert Group:Zhang Fujun (Center for Medical Imaging and Minimally Invasive Cancer, Affiliated Cancer Hospital of Sun Yat-sen University); Wang Junjie (Department of Radiotherapy, Peking University Third Hospital); Guo Jinhe (Department of Radiology and Vascular Intervention, Zhongda Hospital affiliated to Southeast University); Zhang Jianguo (Department of Oral and Maxillofacial Surgery, Peking University Stomatological Hospital); Hu Xiaokun (Interventional Medicine Center, Affiliated Hospital of Qingdao University); Gai Baodong (Department of Gastrointestinal Surgery, China-Japan Friendship Hospital, Jilin University); Chai Shude (Department of Thoracic Surgery, Second Hospital of Tianjin Medical University); Teng Gaojun (Department of Radiology and Vascular Intervention, Zhongda Hospital affiliated to Southeast University); Li Yuliang (Department of Intervention, Second Hospital of Shandong University); Lu Ligong (Interventional Department, Zhujiang People's Hospital); Xiang Hua (Department of Interventional and Vascular Surgery, Hunan Provincial People's Hospital)

In 2009, the National Health Authority¹²⁵I seed implantation therapeutic technologies are included in the third category of medical technologies, and the radioactive¹²⁵I Particle Access and Application Management Specifications. In 2017, the National Health and Family Planning Commission aimed to further guarantee radioactivity¹²⁵I medical quality and safety of seed implantation therapy, will radioactive¹²⁵I Particle implantation therapy changed to restricted medical technology^[1]。 After more than ten years of development, radioactive¹²⁵I seed implantation plays an increasingly prominent role in multidisciplinary comprehensive treatment of tumor^[2,3]。 With the widespread application of this technology, radioactive¹²⁵The radiation protection of I particles has been paid more and more attention. At present, the state has not promulgated radioactive¹²⁵I Criteria for the management of radiation protection in particle wards.

To assess the efficacy and safety of CT-guided iodine-125 seeds in the treatment of intracranial malignancies under control of target and dose.

From November 2003 to May 2016, with the clinical data of 412 operations on 310 patients in 12 hospitals in the past 14 years, this study analyzed the method of CT guided iodine-125 particles brachytherapy in the treatment of intracranial malignant tumors and evaluated the efficacy and complications. Stratification analysis of intracranial malignant tumors was performed.

Overall survival (OS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 67, 41, 26, 23, 46 months respectively.And the progression free time (PFS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 42, 6, 9, 11, 12 months respectively.Various complications were observed with a relatively low incidence of 10.4%.Three cases deceased at an interval of 7-45 days after treatment.

For patients with intracranial malignancies, iodine-125 seeds brachytherapy could achieve a satisfactory treatment efficacy with tolerated complications.Iodine-125 seeds brachytherapy may act as a first-line regimen.

To investigate the characteristics of the distribution and amount of different subtypes of dendritic cell (DC) in myasthenia gravis(MG).

We collected the thymic specimens from 32 patients who received thymoctomy because of cardiac surgery from January 2016 to December 2016 and selected 14 of them as normal control. Meantime, 61 MG patients who combined with thymic hyperplasia and received extended thymectomy were collected and selected 8 of them as experiment group.Immunohistochemical methods were used to label the two subtype DCs: plasmacytoid dendritic cell (pDC) and classical/conventional dendritic cell (cDC), to observe the distribution of these two DC subtypes in thymus and also quantify them in different thymus structures by image analysis software.Comparing with normal thymus of the same age, we intended to demonstrate the characteristics of distribution and density of DC subtypes in patients who had MG and hyperplastic thymus.

(1) We labeled pDC and cDC by staining with CD123 and CD11c.The two DC subtypes distributed in both cortex and medulla, and the majority gathered in medulla, the density of pDC in thymus cortex was (34±6)/mm²(n=14), the density of pDC in thymus medulla was (247±35)/mm²(n=14), the density of cDC in thymus cortex was (21±4)/mm²(n=14), the density of cDC in thymus medulla was (123±16)/mm² (n=14). (2) The density of pDC in thymus cortex and medulla of patients with MG was lower when compared with the normal group (the density of pDC in thymus cortex, [(39±10)/mm² vs (29±5)/mm²], the density of pDC in thymus medulla, [(279±48)/mm² vs (236±49)/mm²], but with no significant difference.There was no significant difference between the density of cDC in thymus cortex of patients with MG patients and normal people, however, the amount of cDC increases in medulla and the difference was statistically significant (P<0.05). (3) The density of cDC in thymus medulla (except for germinal center) was higher than normal people (110±18) /mm² vs (187±29/mm²), though the difference was not statistically significant (P=0.059 9). The density of cDC in the ectopic germinal center (GC) of MG patients increased obviously compared with that in thymus medulla [(203±44) /mm² vs (439±69)/mm²] and the difference was statistically significant (P<0.05).

The density of cDC increases significantly in thymus medulla of MG patients, especially gathering around or in the ectopic GC. It indicates that cDC may play an important role in the formation of ectopic GC in the hyperplasia thymus, thus involves in the disease process.

To analyze prodromal phase and prodromal events of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Clinical data of 179 patients hospitalized and diagnosed during 2010—2016 including adults and children in Peking Union Medical College Hospital and Beijing Children′s Hospital were collected.Patients with prodromal phase or prodromal events were selected.A retrospective analysis of clinical characteristics including prodromal phase or prodromal events, course of disease, brain imaging, laboratory results and therapeutic effect was performed.

Prodromal phase was presented in 31.8% (57/179) of patients.Most common symptoms included fever (73.7%) and headache (68.4%). Prodromal phase was prolonged in 6 patients, the longest being 64 days.Among those 6 patients (10.5%), headache and fever were the only symptoms throughout disease courses in 3 cases.Prodromal events were reported in 6.1% (11/179) of patients, including 5 patients after HSV1 encephalitis, 1 after Japanese encephalitis, and 2 after resection of melanocytic nevi.

Anti-NMDAR encephalitis can be preceded with prolonged prodromal phase.In some patients prodromal symptoms are the only clinical presentation.Clinical features of those atypical cases suggest that infection may be the precipitating factor.Viral encephalitis including HSV1 encephalitis and Japanese encephalitis may be prodromal events in some cases.

To study the relationship between the changes of brain network and cognition in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) by using long term video electroencephalogram (VEEG) and resting-state functional magnetic resonance imaging (RS-fMRI) technology.

Eleven patients with right-handed were recruited (from April 2015 to September 2016) from epilepsy specialist outpatients and functional department of neurosurgery of Tianjin Medical University General Hospital. They all underwent the long term VEEG monitoring (one sleep cycle was included at least). According to the spike-wave index (SWI) during slow ware sleep, they were divided into two groups: SWI<50% (5 cases) and SWI≥50% (6 cases). All the patients were assessed with cognitional test including language, execution, memory and attention. They also underwent the head MRI, RS-fMRI examinations. Then the results were comparatively analysed.

(1)There were no statisticaly significance in sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). The Full Intelligence Quotient (FIQ) (87±18), Verbal Intelligence Quotient (VIQ) (88±15) and Performance Intelligence Quotient (PIQ) (89±20) of SWI≥50% group were lower than SWI<50% group(118±8, 114±11, 119±5) and the differences were statistically significant(P<0.05). (2)There was a negative correlation between the FIQ (P=0.002), VIQ (P=0.006), PIQ (P=0.001) and SWI. The FIQ, VIQ and PIQ had no correlation with the sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). (3)Compared with SWI<50% group, SWI≥50% group showed increased regional homogeneity (ReHo) in the bilateral precentral gyrus, premotor area and the subcortical structure, the right temporal lobe and the bilateral insular lobe(P<0.05); while they showed decreased ReHo in the posterior cingulate gyrus, right posterior inferior temporal lobe and right occipital lobe(P<0.05).

The change of the brain network which is caused by the paradoxical and constant discharge during slow ware sleep in patients with BECTS may affect the development of cognition.

To compare the efficacy of endoscopic endonasal transsphenoidal surgery and microsurgery for pituitary adenomas.

One hundred and ten patients with pituitary adenoma who were treated by single nostril transsphenoidal surgery in the department of neurosurgery of the First Affiliated Hospital of Bengbu Medical College from June 2014 to December 2016 were enrolled.These cases were randomly divided into endoscopic group 53 cases (including 36 cases of functional pituitary adenoma and 17 cases of non-functional pituitary adenoma) and microscope group 57 cases (including 34 cases of pituitary adenoma and 23 cases of non-functional pituitary adenomas), with no significant difference in preoperative clinical data about gender, age, tumor size and endocrine function (P>0.05). The total tumor resection rate, postoperative complication rate and the rate of functional tumor hormone levels were compared between the two groups.

The total resection rate of tumor in patients with endoscope and microscope group were 75.5% (40/53) and 70.2% (40/57) without statistically significant difference (P>0.05). The total resection rate and hormone level decline effective rate of functional pituitary adenomas in neuroendoscope group (91.7%, 33/36; 83.3%, 30/36) were higher than those in microscope group (70.6%, 24/34; 61.8%, 21/34) with statistically significant difference (P<0.05). Another side, there was no statistically significant difference in total resection of non-functional pituitary adenomas between endoscope group (41.2%, 7/17) and microscope group (69.6%, 16/23) (P>0.05). The total incidence of postoperative complications in endoscopic group (9.4%, 5/53) was lower than that in the microscope group (24.6%, 14/57), with statistically significant difference (P<0.05), in which the rate of postoperative complications of functional pituitary adenomas and nonfunctional pituitary adenoma in endoscopy group (8.3%, 3/36; 11.8%, 2/17) and in microscope (20.6%, 7/34; 30.4%, 7/23) had no statistical significance (P>0.05).

Pituitary adenoma resection rate in two ways had no obvious difference, but the advantages of endoscopic surgery for functional pituitary adenomas were obvious.The incidence of postoperative complications of endoscopic surgery was lower than that of microscopic surgery, but there was no difference between functional and non-functional tumors.

To study the correlation between ADC values of diffusion weighted imaging (DWI) and the pathological grading in inflammation activity of chronic hepatitis B, and combined with conventional MRI features to predict the diagnosis effectiveness.

A total of 142 cases of patients with chronic hepatitis B were selected as inflammatory group in 302 Hospital of PLA from January 2014 to December 2015, while 20 cases of healthy subjects without history of liver disease were chosen as control group.All patients underwent MR plain scan and dynamic contrast enhancement and DWI examinations (b=0, 800 s/mm²) for liver, and were performed liver biopsy within two days.According to the degree of inflammation activity (G), the inflammation group was divided into G1, G2 and G3-4 level.The apparent diffusion coefficient (ADC) value, and the MRI features of each group were analyzed.

The ADC values showed statistical difference (F=8.392, P<0.01) within inflammation group of chronic hepatitis B from different pathologic grading, and there was significant negative correlation between ADC values and liver inflammation activity grading (r=-0.613, P<0.01). The ADC value of inflammation group and control group was (1.31±0.16), (1.12±0.15)×10^-3 mm²/s, the difference was statistically significant (P<0.05). The ADC value of G1, G2 and G3-4 level was (1.22±0.12), (1.05±0.12), (0.98±0.10)×10^-3 mm²/s respectively, and there was statistical difference (P<0.05) between G1 and G2, G1 and G3-4. The receiver operating characteristic (ROC) curve in diagnosis of equal and above G2 level showed the area under the curve (AUC) was 0.880, the sensitivity and the specificity was 82.4% and 76.8% respectively, the diagnostic cut-off value was 1.09×10^-3 mm²/s.Besides, the detection rate of portal around its orbit and gallbladder wall edema in inflammation group had statistical difference (P<0.05), and there was no statistical difference in the detection rate of abnormal liver arterial enhancement, hilus lymph node increases and ascites in inflammation group(P>0.05). The ROC in diagnosis of equal and above G2 level by ADC values combined with the MRI characteristic signs showed AUC was 0.938, the sensitivity and the specificity was 88.4% and 88.9% respectively.

ADC values can predict the inflammation activity of chronic hepatitis B with quantitatively and non-invasively.Combining with characteristic MRI signs, ADC values can improve the diagnosis efficiency.

To analyze peripheral blood interleukin-6 (IL-6) promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE).

Blood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed.

The levels of IL-6 mRNA were significantly higher in peripheral blood of SLE.DNA methylation levels of IL-6 promoter were reduced in SLE patients as compared with healthy controls.The methylation status and expression of IL-6 in peripheral blood reflected the levels in peripheral blood mononuclear cells (PBMCs). Significantly positive correlation was found between IL-6 hypomethylation and renal disorder, as well as hypocomplementemia in patients with SLE.

Hypomethylation of interleukin-6 promoter in peripheral blood might be involved in the etiology of SLE.

To investigate the early clinical effects of Dynesys system and transfacet decompression by Wiltse approach in the treatment of lumbar degenerative diseases.

From January 2010 to December 2013, 48 patients suffering from lumbar degenerative diseases were treated with Dynesys system in addition to transfacet decompression through Wiltse approach.There were 28 males and 20 females with age of (51.8±6.8). The preoperative diagnosis included lumbar spinal stenosis(10 cases); lumber intervertebral disc herniation (38 cases). There were 23 cases in L4/5, 16 cases in L5/S1 and 9 cases in both of L4/5 and L5/S1.Posterolateral fixation with Dynesys pedicle screw through Wiltse approach.Unilateral resection of the inferior articular facet of the superior vertebra and the superior articular facet of the inferior vertebra.Decompression of the vertebral canal until the never root was decompressed satisfactorily.In the end, Dynesys was performed according to normal procedure.VAS, ODI evaluating standards were applied to evaluate the therapeutic effect.The intervertebral space and ROM of the lumbar were observed by X ray.

All patients underwent surgery safely without severe complications occurred.The average following up time was 33.5 (24-60) months.Compared with preoperative parameters (7.7±1.3, 70.8±13.5), the scores of VAS and ODI decreased significantly after surgery (2.3±1.5, 23.6±12.2) and at the final follow-up (2.2±1.4, 20.0±9.8) (P<0.05). There were significant difference in the height of intervertebral space and ROM at the stabilized segment (P<0.05), but no significant changes were seen at the adjacent segments (P>0.05). X-ray scan showed neither instability or internal fixation loosen, breakage or distortion in follow-up.

Dynesys system in addition to transfacet decompression through Wiltse approach is a therapy option for mild lumbar degenerative disease.This method can retention the structure of lumbar posterior complex and the activity of the fixed segment, reduce the risk of low back pain together with nerve root decompressed.The early clinical results are satisfactory.

To investigate the clinical characteristics, pathogenesis and surgical strategy for the chronic subdural hematoma associated with arachnoid cyst (AC).

Ten patients of chronic subdural hematoma associated with AC were retrospectively enrolled from the Neurosurgery Department of Tianjin Medical University General Hospital from January 2012 to September 2015, with a mean age of 27.5±5.6 years (range, 18-37 years). All patients simply performed a burr hole drainage of hematoma and left the AC intact, then followed up for 12 to 18 months after discharge respectively.

In this study, the AC in 8 of 10 cases occurs in the middle cranial fossa, and the other 2 cases root in the cerebral hemisphere.The AC of 10 patients all locate near the hematoma cavity.Nine patients had a full recovery, and only one patient had a recurrent subdural hematoma with a secondary operation, then recovery in 3 months postoperation.All patients lived completely free of neurological symptom and showed no recurrence in the follow-up period with a Barthel index more than 90.

Simply burr hole drainage of hematoma and leave intact AC achieves satisfied outcome and provides a reliable therapy strategy for chronic subdural hematoma associated with arachnoid cyst.

To investigate the effect of neuroglobin on oxygen-glucose deprivation and reoxygenation (OGD/R) induced autophagy in a human neuroblastoma cell line (SH-SY5Y).

SH-SY5Y cells were transfected with plasmids (or vector) to establish a stable cell line of NGB overexpression (OE). After treated with OGD/R, cells were collected for the analyses of mRNA (Atg5, Atg7, BECN1 and FUNDC1) and protein levels of LC3. Furthermore, mitochondrial and cytosolic fractions were isolated for protein levels of PINK1 and Parkin.

Treatment of OGD/R significantly increased the levels of mRNA of Atg5, Atg7, BECN1 and FUNDC1 (peak levels were 4.90±0.71, 6.72±0.75, 2.71±0.39 and 3.96±0.78 fold, all P<0.05). The protein level of Parkin increased in mitochondria and decreased in cytoplasm after the treatment. Compared with the vector group, Ngb OE group showed a significant higher level of FUNDC1 mRNA (3.96±0.78 versus 6.86±0.63 fold,P<0.05), while Atg5, Atg7 and BECN1 mRNA levels showed no significant difference. Moreover, the mitochondrial or cytosolic protein levels of PINK1 or Parkin showed no significant difference between Ngb OE and vector group.

Overexpression of Ngb can not affect autophagy or mitohpagy in OGD/R treated SH-SY5Y cells. Overexpression of Ngb can increase the mRNA level of FUNDC1 and the mechanism needs further study.

To investigate the combination effect of anti-tumor agent rapamycin and anti-autophagy agent chloroquine on osteosarcoma.

The inhibition effect of rapamycin or chloroquine and combination of both on human osteosarcoma cell line 143B measured with CCK-8 box.The combination index at different concentration was calculated, and the synergism effect range was analysed.The effect of combined therapy on cell cycle and apoptosis via flow cytometric was analyzted.Setting up murine subcutaneous xenograft model, the combination effect of antitumor in vivo observed.

Either of them, rapamycin or chloroquine had an antitumor effect in vitro (RAPA: IC50=1.5 nmol/L; CQ: IC50=400 μmol/L). When the inhibition rate 40%<fa<70%, the combination had synergism effect (CI<1) at different concentration.Moreover, when CQ at 200 μmol/L, the synergism effect was the most obvious, CI _min=0.255.The flow cytometric analysis display rapamycin at 1.5 nmol/L had slightly promote apoptosis effect (16.1%±4.4%), and had distinct cell cycle arrest, mainly blocked at G0/G1 phase (73.5%±10.6%; control group: 46.7%±7.7%; P<0.001). While combined with chloroquine, the apoptosis cell obviously increased (21.3%±6.8%;P<0.05). The xenograft model also confirmed that rapamycin combined with chloroquine had a better antitumor effect than single usage (relative tumor proliferation rate; T/C%.CQ: 98.4%±11.6%; RAPA: 65.5%±7.5%; CQ+ RAPA: 42.0%±3.4%).

Rapamycin combine with chloroquine can increase the antitumor efficacy, and the combination therapy maybe a potential therapeutic regimen.

A 56-year-old male was admitted to Guangzhou First People's Hospital on August 1, 2016 due to "sudden squeeze-like chest pain for 3 h". Body weight 62 kg. No previous drug or family allergy history. Physical examination at admission: body temperature 36.1 ℃, 19 breaths/min, 105 pulses/min, blood pressure 153/85 mmHg (1 mmHg =0.133 kPa). The mind was clear, there was no bleeding or rash on the skin and mucous membranes, the breathing sounds of both lungs were clear, no cardiopathological murmur was heard, the bilateral radial artery pulsed well, and the limbs were not swollen. The electrocardiogram showed a dorsal upward elevation of 0.2~0.5 mV in the ST segment of leads V1~ V5. Color ultrasound showed left atrial enlargement, mild mitral insufficiency, reduced anterior wall movement, and normal left ventricular systolic function. GRACE had a danger score of 101 and CRUSADE had a bleed score of 26. Emergency myocardial examination of three items: myoglobin 1 597.1 ng/ml, troponin I 80 ng/ml, creatine kinase MB isoenzyme Ⅱ 240.2 ng/ml. Hemoglobin 161 g/L, platelets 233×10⁹/L. Blood coagulation function was normal. Coronary heart disease diagnosed after admission: acute extensive anterior wall myocardial infarction. After admission, he was treated with aspirin 300 mg and clobigrel 300 mg oral loading. The patient refused direct interventional surgery due to poor economic conditions. After comprehensive evaluation, there was indication of thrombolysis, and thrombolytic therapy with alteplase was performed. The puncture vein of the right forearm failed. Instead, the puncture vein of the left forearm was successfully placed with an indwelling needle for thrombolysis. Before thrombolysis, 3 000 U of unfractionated heparin was given to heparinization. It was planned to give alteplase 100 mg (Boehringer Ingelheim Pharmaceuticals, Germany) for 90 minutes. First, 15 mg was intravenously injected, followed by continuous intravenous drip of 50 mg for 30 minutes, and the remaining 35 mg was continuously intravenously injected for 60 minutes. About 1 hour after the start of thrombolysis, the patient felt swelling in the right forearm, and soon blood blisters and blisters appeared (Figure 1), blood pressure was measured at 130/70 mmHg, alteplase was discontinued immediately, and local symptoms were further aggravated after 2 h (Figure 2), the right radial artery pulsed normally, the skin of the right hand was slightly cooler, and the circumference of the right forearm was 3~4 cm larger than that of the left forearm. Emergency ultrasound showed no hematoma, no abnormalities in arteries and veins, only thickening of subcutaneous tissue. Fibrinogen was 3.01 g/L before thrombolysis, which was undetectable the next day. Hemoglobin was 161 g/L before thrombolysis and 108 g/L on day 3. No bleeding was found in other parts such as the digestive tract, and no red blood cells were transfused. Monitor the patient's vital signs closely, raise the affected limb, drain by gravity, pierce large blood blisters with a sterile needle, cover with petrolatum oil gauze, then cover with sterile ordinary gauze block, and then apply magnesium sulfate wet compress for 1 d, then change to boric acid gauze block wet compress, take Willitan orally, and use sodium aescin intravenously. It began to improve after 1 d, and further improved on the 4th day. To Day 6 (Figure 3), the patient's bleeding performance improved significantly, and there was no chest pain attack after using the above hemostatic drugs. On the 9th day, the patient did not want to stay in hospital for too long due to poor economic conditions, and insisted on discharge. After 3 months of follow-up, the condition was good, the skin of the right upper limb completely healed, and the hemoglobin rose to 130 g/L.

With the increasing infertility rate (about 12.5% ~15%), assisted reproductive technology (ART) has become the first clinical choice to solve this problem. At the same time, there are also many problems such as low embryo implantation rate and birth rate (about 50% and 35% respectively), high congenital defect rate (0.5% ~1%), abnormal glucose metabolism, changes in DNA methylation pattern and changes in the expression of imprinted genes (such as H19), etc^[1]。 Embryos have very stringent requirements for in vitro culture environment, O₂Concentration, amino acid composition, mineral oil coverage, culture volume, culture density, temperature, humidity, pH value and artificial micromanipulation pressure may cause abnormal embryo development, among which light is also one of the important influencing factors^[2]。 In the natural state, female reproduction and embryo growth and development are completely protected from light, but ART means expose gametes and embryos to various wavelengths and intensities of light sources: microscope light source, indoor lighting and outdoor light, among which microscope light is the most serious influence^[3]。 It is of great significance and value to study and clarify the influence of light on early embryo development in ensuring embryo safety and offspring health. This article will summarize and discuss from the following aspects.