Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Combining bi-modal imaging and immunohistochemical indicators to predict axillary lymph nodes status in cN 1 breast cancer patients receiving neoadjuvant chemotherapy / 中华超声影像学杂志

Objective:To investigate whether ultrasound features, mammographic features and immunohistochemical indicators show any association with rates of axillary pathologic complete response(pCR) in cN 1 breast cancer patients receiving neoadjuvant chemotherapy(NAC), and to construct prediction models of axillary pCR to predict axillary lymph nodes (ALN) status, so as to select suitable patients for less invasive axillary surgery after NAC. Methods:This retrospective study evaluated 134 consecutive cN 1 breast cancer patients with ALN metastasis who underwent NAC in the Second Affiliated Hospital and Tumor Hospital of Harbin Medical University from July 2020 to July 2022. According to the pathological results of ALN surgery after NAC, the cases were divided into pCR and non pathologic complete respose(npCR) groups. The ultrasound images, mammographic images and immunohistochemical indicators of the two groups were compared. In terms of logistic regression algorithm, the model A(the ultrasound model), the model B(the ultrasound combined with mammography model), the model C(the ultrasound combined with immunohistochemistry model) and the model D(the ultrasound combined with mammography and immunohistochemistry model) were respectively established for predicting the pathological state of axillary lymph nodes in breast cancer patients, ROC curves were plotted to evaluate the performance of the models, and the diagnostic efficiency of different models was compared by Delong′s test. The model with the best predictive performance was shown in a nomogram. Results:①The P values between two groups of the short diameter of ALN, the ratio of long/short diameter of ALN, fatty hilum and central hilar vascularity, mammographic spiculation, estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor 2(HER2) were <0.05 by the t test and χ 2 test analysis. ②The ratio of long/short diameter and fatty hilum in the model A were independent factors for predicting the pathological status of ALN after NAC. The independent predictors of model B and Model C were respectively added with mammographic spiculation and immunohistochemical indicators (ER, PR) on the basis of model A. In the model D, the ratio of long/short diameter, short diameter, fatty hilum, mammographic spiculation, and immunohistochemical indicators (ER, PR) remained significant independent predictors associated with axillary pCR. ③The area under ROC curve (AUC) of the model A, B, C, D was 0.78, 0.84, 0.84 and 0.89, respectively. The sensitivity was 0.71, 0.80, 0.78 and 0.86, the specificity was 0.76, 0.74, 0.76 and 0.80, and the accuracy was 0.73, 0.76, 0.77 and 0.83, respectively. ④Delong′s test showed the model D had an improved AUC of 0.89(0.89 vs 0.78, 0.84, 0.84, all P<0.05). Conclusions:The prediction models combining bi-modal imaging and immunohistochemical indicators show good prediction ability and can provide reference for selecting suitable patients for less invasive axillary surgery after NAC.

Prediction of Ki-67 expression level in mass breast cancers using multi-modal ultrasound features / 中华超声影像学杂志

Objective:To predict the Ki-67 expression grading in patients with mass breast cancer based on multimodal ultrasound features to aid clinical diagnosis and treatment.Methods:Ninety-three female patients (93 masses in total) with breast cancers confirmed by pathological examination were retrospectively included in the Second Affiliated Hospital of Harbin Medical University from September 2017 to September 2020. According to the immunohistochemical results, the patients were divided into Ki-67 high expression group (55 cases) and Ki-67 low expression group (38 cases). The qualitative and quantitative features from two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) images of all breast masses were retrospectively analyzed, differential features were analyzed based on logistic regression algorithm. ROC curves and Kappa test were used for the evaluation of diagnosis.Results:The univariate analysis revealed statistically significant differences between the two groups for conventional ultrasound features (size, shape, margins), SWE features (stiff rim sign, Eratio), and CEUS features (perfusion defect, IMAX) (all P<0.05). In the multiple logistic regression analysis, the margins, stiff rim sign, and perfusion defect were the independent factors for predicting the Ki-67 expression (all P<0.05). The performance of the predictive model was 0.882 (95%confidence interval of 0.798-0.940, P<0.05) with the sensitivity of 0.818 and specificity of 0.790. Conclusions:A preliminary analysis of the relationship between multi-modal ultrasound features and Ki-67 expression grading in mass breast cancers was performed based on logistic regression algorithm to provide more imaging information for clinical treatment and prognosis assessment.

Effect of obesity induced by high-fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus surgery in young mice / 药学学报

Obesity is an important risk factor related to osteoarthritis, but it′s role in post-traumatic osteoarthritis on young people need to further study. The internal mechanism except the mechanical loading may be associated with adipose exosomes. To examine the effect of obesity induced by high fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus (DMM) surgery in young mice, 20 6-week-old C57BL/6J mice were randomly assigned to the control diet group (CD, n = 5), the DMM group (n = 5), the high fat diet group (HFD, n = 5) and the HFD plus DMM group (HFD+DMM, n = 5). The CD and DMM group were fed with a control diet, and the HFD and HFD+DMM group were fed with a high fat diet. We did the DMM surgery and the sham surgery on the mice when it was 10 weeks old. Extract obese and normal adipose exosomes, identify exosomes in vitro, and proceed fluorescence imaging in vivo using DiR staining. DMM+HFD-Exo group and DMM+CD-Exo group were injected the exosomes from the tail vain once a week (100 μL per shot with a concentration of 1 μg·μL-1). Second, 15 6-week-old C57BL/6J mice were randomly assigned to the DMM group (n = 5), the DMM plus obese adipose exosomes group (DMM+HFD-Exo, n = 5), and the DMM plus control diet adipose exosomes group (DMM+CD-Exo, n = 5). Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Nanjing University (IACUC-D2204005). All mice were sacrificed at the age of 18 weeks, the knee joints of the mice were harvested and fixed. We used micro CT to examine the samples and measured the bone volume/tissue volume, trabecular thickness, trabecular number and trabecular separation. Then the samples were decalcified and embedded in paraffin, and 4 μm thickness sections were stained with H&E and safranin O/fast green to observe the histological changes of the knee joint. The results showed compared with the control diet group, high fat diet induced obesity can aggravate the pathological changes of the post-traumatic osteoarthritis caused by DMM surgery, which shows in having a higher Mankin score. The surface of knee articular cartilage in the HFD+DMM group was rough, and the subchondral bone has an increase in bone sclerosis. Compared with the DMM group, obese adipose exosomes can exacerbate the pathological changes of the knee articular cartilage, while not influencing the subchondral bone. In conclusion, high fat diet induced obesity can aggravate the post-traumatic osteoarthritis caused by DMM surgery in young mice. The obese adipose exosomes mainly affect the surface of the knee articular cartilage.

Construction and optimization of a novel plasma membrane model for membrane affinity assay based on polydiacetylene vesicles / 药学学报

Most drugs need to interact with cell membrane to reach the biological target, so that membrane affinity assay is an important early screening step in drug discovery. However, at present, the traditional oil-water distribution method is still used, a new, simple and accurate method for membrane affinity assay is urgently needed. In this study, according to the colorimetric principle, a new assay model based on polydiacetylene vesicles was optimized through a series of experiments including different concentrations of vesicle solution, temperature, or pH reaction environment. On this basis, tetracaine hydrochloride, 2-methylimidazole and histamine were used as model drugs to measure the membrane affinity constants and verify the between-batch precision of the optimized assay model (relative standard deviation less than 5%). In addition, polydiacetylene vesicles were stable for up to 180 days, demonstrating the potential application of the assay model. This strategy is simple, stable, reliable, with high reproducibility, low cost and easy to promote, which provided a new tool and a new direction for the high-throughput assay of membrane affinity.

Herbal Textual Research on Gei Herba and Its Pharmacological Effect on Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Gei Herba is a traditional folk herbal medicine with a variety of functions such as replenishing Qi and invigorating spleen， tonifying blood and nourishing Yin， moistening lung and resolving phlegm， activating blood and alleviating edema， moving Qi， and activating blood. The reports about the pharmacological effects of this herbal medicine have been increasing in recent years. By reviewing the ancient and modern literature about Gei Herba， we systematically organized the name， original plants， nature， taste， and functions of this herbal medicine， and summarized the modern pharmacological studies and clinical applications of Gei Herba in cardiovascular and cerebrovascular diseases. Gei Herba was first recorded in the name of "Dijiao" in the Geng Xin Yu Ce（《庚辛玉册》） written in the Ming Dynasty. It is derived from Geum japonicum var. chinense （Rosaceae） and sometimes confused with Adina rubella （Rubiaceae）. This medicine had numerous synonyms in the local materia medica books. Gei Herba is widely distributed and harvested in summer and autumn， with the dried whole grass used as medicine. The historical records of the nature， taste， meridian tropism， main functions， and indications of Gei Herba are not consistent. It is generally believed that Gei Herba is pungent， bitter， sweet， cool， and has tropism to the liver， spleen， and lung meridians. Based on the effects of tonifying Qi， activating blood， and nourishing Yin， modern pharmacological studies have reported that the extracts of Gei Herba and the tannin phenolic acid compounds and triterpenoids isolated from Gei Herba have therapeutic effects on cardiovascular and cerebrovascular diseases such as hypertension， myocardial ischemia， cerebral ischemia， and vascular dementia. This study provides a reference for discovering the clinical advantages of Gei Herba and developing new drugs.

Assessment of conventional magnetic resonance morphological measurements in diagnosis and differential diagnosis of progressive supranuclear paralysis / 中华老年医学杂志

Objective:To study the features as well as the diagnosis and differential diagnosis values by conventional MRI morphometrics in different clinical subtypes of progressive supranuclear palsy(PSP).Methods:Forty five patients with PSP were included, comprising three PSP subtypes: 15 cases of Richardson's syndrome(PSP-RS), 15 cases of Parkinson's syndrome(PSP-P)and 15 cases of progressive frozen gait(PSP-PFG). In addition, three control groups were established: 15 cases of multiple system atrophy-Parkinson's syndrome(MSA-P), 30 cases of primary Parkinson's disease(PD)and 40 healthy controls(HC). Midbrain area-to-Pons area ratio(M/P), Magnetic Resonance Parkinsonism Index(MRPI, MRPI2.0), width ratio of middle cerebellar peduncle to superior cerebellar peduncle(MCP/SCP), Midbrain-to-Pons ratio(MTPR), Angle of cerebral peduncle(A cp), third ventricle width/frontal horns width ratio(V 3rd/FH), and Humming bird sign rating scale(HBS-RS)scores were calculated.Diagnostic sensitivity and specificity were performed by ROC curve to assess the accuracy of these imaging indicators in the diagnosis and differential diagnosis of PSP and its subtypes. Results:The MRPI, MRPI2.0, MCP/SCP and HBS-RS scores were significantly higher in PSP group than in other control groups( H=69.351, 66.776, 33.926 and 84.694, all P<0.05), while M/P and MTPR were significantly lower in PSP group than in other control groups(H=60.101 and 77.276, all P<0.05). PSP group also had higher V 3rd/FH compared with PD or HC group( F=17.168, P<0.05), but not with MSA-P group( Z=-1.602, P>0.05). The above differences also existed between each PSP subgroup and control groups.Among PSP subgroups, PSP-PFG subgroup had a larger A cp than did PSP-RS( Z=-2.510, P<0.05), and had higher HBS-RS score than did PSP-P group( Z=-2.380, P<0.05). No significant differences in other MRI morphometric indexes were identified among PSP subtypes.The M/P, MRPI, MTPR, MRPI2.0, HBS-RS score showed good accuracy in diagnosing PSP and its each subgroup, with HBS-RS score being the most accurate indicator, when the cutoff value was 2, the AUC values were all higher than 0.99, and the sensitivity and specificity were all above 90%.PSP and its subtypes were best distinguished from MSA-P by MRPI, when the cutoff value was 9.94, the AUC values were all higher than 0.90, with the sensitivity of 100% and specificity of 86.67%.PSP and its subtypes were best distinguished from PD by MTPR, AUC values were all above 0.95, with slightly different cutoff values.Almost all the morphological measurement parameters failed to show significant sensitivity and specificity in discriminating subtypes of PSP.The sensitivity and specificity of almost all MRI morphometry indicators in differentiating different subtypes of PSP are not high. Conclusions:MRI morphometrics have a high value both in the diagnosis of PSP and its subtypes, and also in specific application fields.MRI morphometrics have a limited value in discriminating PSP subtypes.

Discussion on the relationship between yuan-source points of yang meridians and diseases of fu- organs / 中国针灸

Huangdi Neijing (Yellow Emperor 's Canon of Medicine) establishes the theory that yuan-source points are indicated in zangfu diseases. However, compared with the yuan-source points of yin meridians for the treatment of zang-organ diseases, there is less attention to the indication of yuan-source points of yang meridians for fu-organ diseases, and this statement is even questioned. Collating the early literature and associating with the researches of medical experts, it is found that Nanjing (Classic of Difficult Questions) should be the theoretic origin that yuan-source points of yang meridians are indicated in fu-organ diseases. Regarding the reasons why this theory has not received clinical attention, the three aspects are involved, i.e. the theoretic completion of "he-sea points of three-foot-yang meridians for the diseases of six fu-organs", the limitation of the theory itself, and the lack of literature materials. It is proposed that the exploration on this theory should be deepened in views of the essence of yuan-source points relevant with the characteristic of the wrist-ankle pulse palpation region, acupoint combination, modern technology, etc.

Role of sclerostin in the occurrence and development of uveal melanoma and its biological mechanism / 中华实验眼科杂志

Objective:To investigate the effects of sclerostin (SOST) and WNT/CTNNB1 signaling pathway on the cell cycle, migration and invasion of human uveal melanoma (UM) cells and its related mechanism.Methods:UM tissues from 20 cases of epithelioid UM and 16 cases of spindle cell type UM were collected.The contents of SOST, Wnt-1 and Catenin beta-1 proteins in the collected tissues were detected by immunohistochemical staining.Three human UM tissue derived cell lines OCM-1 (primary spindle cell type), Mum-2B (metastatic epithelioid) and Mum-2C (metastatic spindle cell type) were selected and divided into three groups, blank control group not transfected, empty vector group transfected with SOST negative control vector and SOST siRNA group transfected with SOST siRNA.After 24-hour transfection, the mRNA and protein expression levels of SOST, CTNNB1, WNT protein family 1 (WNT1), CCND1, matrix metalloproteinase (MMP)2 and MMP9 were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The invasion and migration ability of the transfected cells were measured by transwell method, and the cell cycle distribution was detected by flow cytometry.Another 9 female BALB/c nude mice were selected and randomized into OCM-1 group, OCM-1 empty vector group and SOST shRNA group, inoculated with OCM-1 without lentivirus infection, OCM-1 with blank lentivirus infection and OCM-1 with SOST shRNA lentivirus infection, respectively.Six weeks after inoculation, the in situ formation of tumor was observed.The interaction between SOST and low density lipoprotein receptor related protein(LRP)-5/6 in OCM-1 cells was explored by co-immunoprecipitation assay.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2018KY[L]-20).Results:Immunohistochemical staining results showed that the SOST expression level was higher and the expression levels of Wnt-1 and Catenin beta-1 were lower in spindle cell type UM tissues than in epithelioid UM tissues, and the differences were all statistically significant (all at P<0.01). The real-time fluorescence quantitative PCR results showed that the relative expression of SOST mRNA was significantly lower and the relative expressions of CCND1, WNT1 and MMP9 mRNA were significantly higher in SOST siRNA groups than in corresponding empty vector groups in the three cell lines (all at P<0.05). In OCM-1 and Mum-2C cell lines, the relative expressions of CTNNB1 mRNA were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Western blot results showed that the relative expression of SOST protein was significantly lower and the relative expressions of Wnt-1, Catenin beta-1, cyclin-D1, MMP2 and MMP9 proteins were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Transwell assay showed that the cell invasion and migration ability of SOST siRNA group was significantly higher than that of blank control group and empty vector group in the three cell lines (all at P<0.01). Flow cytometry showed that the proportion of G1-phase cells and the G1/S-phase ratio were significantly lower in SOST siRNA group than in blank control groups and empty vector groups (all at P<0.01). The eyeball volume of OCM-1 group, OCM-1 empty vector group and SOST shRNA group was (42.7±4.6), (49.0±22.9) and (135.2±32.7)mm 3, respectively, showing a significant overall difference ( F=19.963, P<0.01). The eyeball volume of SOST shRNA group was larger than that of OCM-1 group and OCM-1 empty vector group, and the differences were statistically significant (both at P<0.05). Co-immunoprecipitation results showed that SOST could interact with LRP-5 and LRP-6 by binding to them, respectively. Conclusions:Silencing SOST can promote the invasion and migration of UM cells, and increase the proportion of UM cells in the division phase.Silencing SOST can promote tumor growth in eyes of nude mice.SOST may play this function by interacting with the membrane receptor LRP-5/LRP-6 and then regulating the WNT/CTNNB1 signal pathway.

Comparison study of clinical features between persistent hyperplastic primary vitreous and congenital fibrovascular pupillary membrane / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the similarities and differences of the clinical features between persistent hyperplastic primary vitreous(PHPV)and congenital fibrovascular pupillary membrane(CFPM).METHODS: Retrospectively analyze the ocular biometric parameters, clinical features and morphological changes in children with PHPV(PHPV group)and CFPM(CFPM group)who received surgery at the department of ophthalmology, Xijing Hospital from March 2006 to December 2021.RESULTS: The study included 56 cases(61 eyes)of PHPV and 24 cases(25 eyes)of CFPM. There were no differences on the gender and age of onset between PHPV and CFPM, and both of them were mainly unilaterally affected, with the ratio of 91% and 96%. Children with PHPV and cataract combined with other complications and ocular developmental abnormalities. CFPM was mainly presented different degrees of blockage and morphological abnormalities of pupillary area. In unilateral cases of PHPV and CFPM, the anterior chamber depth(ACD)of affected eyes was smaller than that of the fellow eyes, and in subgroups with age of operation ≤24mo, the axial length(AL)of affected eyes was smaller than that of the fellow eyes(P&#x003C;0.05). The corneal diameter(CD)of the affected eyes in PHPV group was smaller and the intraocular pressure(IOP)was higher than those of the fellow eyes(all P&#x003C;0.05); while there were no significant differences on CD and IOP between affected eyes and the fellow eyes in CFPM group(P&#x0026;#x003E;0.05). The ACD of affected eyes in PHPV group was significantly smaller than that of CFPM group(P&#x003C;0.05). The fibrovascular membrane in PHPV group was located in the posterior part of the lens and vitreous cavity; while the fibrovascular membrane in CFPM group was located between the iris and the anterior capsule of the lens, rarely involving the lens.CONCLUSION: PHPV and CFPM had the similar clinical features, suggesting that they may belong to the different variants of persistent fetal vasculature(PFV). However, PHPV had a wider range of lesions and more complex conditions.

Progress in research of risk prediction of non-syndromic oral clefts using genetic information / 中华流行病学杂志

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.

Application of perceptual learning in amblyopia treatment / 国际眼科杂志(Guoji Yanke Zazhi)

@#Amblyopia is a common eye disease in children. In recent years, people have been exploring new treatments for amblyopia patients with poor results of the traditional treatment. In the field of visual cognition, some computer programs and video games are widely used to improve the functions of the visual system. Based on the perceptual learning, new methods such as video games, dichotomous stimulation, and stereo vision training are proposed to treat amblyopia. This article combines domestic and foreign research on perceptual learning and other emerging methods. The application of therapies in the treatment of amblyopia was reviewed, the effects of different methods in the treatment of amblyopia were analyzed. Combined with the existing problems, the future development of this field was further discussed.

A novel small molecule anti-VEGF drug Brolucizumab in the treatment of neovascular age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

@#Anti-vascular endothelial growth factor(anti-VEGF)drugs have become the first choice for the treatment of intraocular neovascularization, but the inconvenience and possible complications caused by frequent intravitreal injection cannot be ignored. Therefore, it is necessary to seek new drugs with long-lasting effects, so as to reduce the number of injections. Brolucizumab, a novel small molecule anti-VEGF drug, has the advantages of stronger tissue penetration, higher drug concentration, smaller injection dose, long-lasting efficacy and longer injection interval. Registered clinical studies and real-world evidence showed that Brolucizumab is non-inferior to aflibercept in efficacy, while its ability to improve intraretinal/subretinal fluid is more significant, and it can maintain a longer dosing interval. In addition, Brolucizumab is safe and has a low incidence of serious adverse events, such as retinal vasculitis reported. Brolucizumab provides a new treatment option for neovascular age-related macular degeneration(nARMD). This article reviews the latest progress of Brolucizumab in the treatment of nARMD.

New advances in the precision diagnosis and treatment of liver cancer / 临床肝胆病杂志

Liver cancer is a global challenge that greatly threatens human health, and early identification, early diagnosis, and early treatment are the key to effectively improving quality of life and prolonging survival time for liver cancer patients. Liver cancer has complex pathogeneses, diverse etiologies, and significant heterogeneity between individuals, and early diagnosis and effective treatment have always been difficult issues. Under the guidance of the concept of precision medicine, innovative thoughts combining modern techniques with traditional methods are expected to solve the mystery of disease onset through multidisciplinary integration, thereby achieving new breakthroughs in the diagnosis and treatment of liver cancer.

Cloning and tissue expression analysis of the LepROT gene of Rana dybowskii / 生物工程学报

Leptin receptor overlapping transcript (LepROT) plays multiple roles in the regulation of immune systems. However, very little information is available about the anti-infectious mechanisms of amphibians LepROT. In this study, the cDNA sequence of the Rana dybowskii LepROT gene was determined by using RT-PCR and bioinformatics analysis. Then, the Aeromonas hydrophila (Ah) and lipopolysaccharides (LPS) infected models of R. dybowskii was constructed to obtain histopathological characteristics. Constitutive expression of LepROT mRNA and NF-κB signaling pathway were detected by real-time quantitative PCR. The full-length cDNA of LepROT gene was 396 bp and encoded 131 amino acids. Amino acid sequence analysis revealed LepROT shares 93.74% and 86.39% identity with homologues from other amphibians and mammals respectively, and the LepROT gene was quite conserved among different species. After infection, the relative expression levels of LepROT, NF-κB, IKKα and IKKβ mRNA were all significantly upregulated (P < 0.01), but showed a diverse temporal pattern of up-regulation in different tissues. Therefore, it was proposed that the LepROT gene of R. dybowskii might activate the NF-κB signaling pathway to exert anti-infectious effects, thus providing evidence for further extending the biological function of LepROT.

Research progress of novel small molecule anti-VEGF drug Brolucizumab in the treatment of diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic macular edema(DME)has become the leading cause of vision loss in patients with diabetes. Currently, intravitreal injection of anti-vascular endothelial growth factor(VEGF)therapy is the first-line treatment for DME. However, the economic burden and related complications brought by frequent injections should not be ignored. Therefore, the drugs with longer-lasting effects and longer injection intervals must be explored. Brolucizumab is a single-chain antibody fragment(scFv)with a high affinity for VEGF. Compared with other available anti-VEGFs, it has the characteristics of smaller molecular weight, higher tissue permeability and durable therapeutic effect. Clinical studies and real-world evidences showed that Brolucizumab is non-inferior to aflibercept in improving visual acuity in patients with DME. And Brolucizumab is more effective in regressing intra-retinal fluid and reducing central foveal thickness(CSFT)with longer injection interval. At the same time, Brolucizumab has a low incidence of adverse events and favourable safety after intraocular injection. This article reviews the latest progress of Brolucizumab in the treatment of DME.

Evaluation of the pathological status of axillary lymph nodes after neoadjuvant chemotherapy based on multimodal ultrasound characteristics for breast cancer / 中华超声影像学杂志

Objective:To construct a diagnostic model based on the multimodal ultrasound imaging, and to predict the axillary lymph node (ALN) status of breast cancer patients after neoadjuvant chemotherapy (NAC).Methods:A total of 204 female breast cancer patients with ALN metastasis who had undergone puncture biopsy of aspiration in the Second Affiliated Hospital and Harbin Medical University Cancer Hospital between July 2017 to May 2021 were included. According to the pathological results of ALN surgery after NAC, the cases were divided into pathologically complete response (pCR) group and non-pCR group. The ultrasound images, immunohistochemistry and blood routine index were collected and compared between the two groups, the indexes whose P<0.02 were selected. In terms of logistic regression algorithm, a predictive model for the pathological state of axillary lymph nodes in breast cancer patients was established after NAC, and ROC curve was plotted to evaluate the performance of the model. Results:The P values for comparison between the two groups of the breast tumor size, blood flow resistance index (RI), elasticity score, lymph hilum structure, maximum cortical thickness, blood flow distribution, blood flow RI, and immunohistochemical detection indicators including estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor 2(HER-2), Ki67 molecular expressions were <0.20 by t test, Mann-Whitney U test, and χ 2 test analysis; in the multiple logistic regression analysis, tumor size, lymphatic hilum structure, maximum cortical thickness, lymph node blood flow distribution and blood flow resistance index, PR and HER-2 molecular expressions were the independent factors predicting the pathological status of axillary lymph nodes in breast cancer patients after NAC ( P<0.05). The performance of the predictive model was 0.870 (95% confidence interval: 0.819-0.922, P<0.05), with sensitivity of 86.82% and specificity of 70.67%. Conclusions:The model for predicting the pathological state of ALN in breast cancer patients after NAC using multi-modal ultrasound characteristic and immunohistochemical indexes achieves good diagnostic performance providing more objective evidence for the formulation of clinical treatment plans and prognostic evaluation.

Time phased scheduling and Disease grading management to achieve efficient rescue of batches of COVID-19 infected patients in shelter hospital / 中华急诊医学杂志

Objective:To introduce how to quickly set up a doctor team to achieve efficient treatment of batchs COVID-19 patients in Changchun GongTi shelter hospital.Methods:A cross-sectional study was conducted to analyze the basic situation of the doctors who supported the Changchun Gongti shelter hospital. The workload is the total number of patients from April 3 to 28, 2022. At the beginning of the task, the first week and the third week of the task, the five point scoring method was used to reflect the doctor's physical and mental state, stress state and rescue achievement. The time phased scheduling and disease grading management were fully implemented after 10 days of operation in the shelter. The doctors' ward round efficiency and self scoring changes before and after the implementation of the plan were compared, and the rescue results were summarized.Results:Total of 56 doctors (the Sichuan medical assistance team to Changchun), who undertook the work of Changchun Gongti shelter Hospital, came from 12 professional departments of 14 hospitals. By internal and external linkage-time phased scheduling and information-based patient zoning and grading management, the admission time of batch patients was shortened from (14.64±10.09) min to (6.80±5.10) min per person( P<0.05), the number of patients that each doctor can view per hour ranges from (28.50±12.26) to (68.43±19.95) ( P<0.01). A total of 1 293 patients were treated. There were no deaths, no accidents and no mild illness to severe illness in shelter hospital. 35 doctors completed a continuous survey. Before and after the implementation of those measures, the average physical state scores and the psychological state scores of doctors improved ( P=0.03), the self-score of stress feeling decreased ( P<0.01), and the self-score of professional achievement increased ( P<0.01). Conclusions:To adapt to the characteristics of emergency treatment for batch COVID-19 patients, the internal and external linkage-time phased scheduling and information-based patient zoning and grading management could help the temporarily convened doctors deal with a large number of patients efficiently, reduce work stress and exposure risk in shelter hospital.

Mechanisms of ferroptosis in microglial cell line BV-2 cells after lead acetate exposure / 环境与职业医学

Background Lead exposure induces microglial cell death, of which the mechanism is unclear. Ferroptosis is a new death form and its role in microglia death has not been reported. Objective To investigate the role of ferroptosis in microglia following lead exposure in order to provide a theoretical basis for the mechanism of lead neurotoxicity. Methods Microglial cell line BV-2 cells were co-cultured with 0, 10, 20 and 40 μmol·L−1 lead acetate for 24 h. The 40 μmol·L−1 lead acetate group with iron chelator (DFO) was named the 40+DFO group. Changes in BV-2 cell morphology after lead exposure were observed under an inverted microscope; tissue iron kit and glutathione kit were used to detect intracellular iron and glutathione (GSH) respectively; flow cytometry was applied to detect lipid reactive oxygen species (lipid ROS) immunofluorescence intensity. Western blotting and qPCR were adopted to detect the expressions of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor 1 (TFR-1), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1) protein and mRNA. Results Compared with the control group, the number of BV-2 cells decreased with increasing doses of lead and the cells showed a large, round amoeboid shape. The intracellular levels of iron of BV-2 cells were (1.08±0.04), (1.29±0.03), and (1.72±0.10) mg·g−1 (calculated by protein, thereafter) in the 10, 20, and 40 μmol·L−1 lead acetate groups, respectively, significantly higher than that in the control group (P<0.05), and the intracellular level of iron in the 40+DFO group, (1.34±0.10) mg·g−1, was lower than that in the 40 μmol·L−1 lead acetate group, (1.72±0.03) mg·g−1 (P<0.05). Compared with the control group, the TFR-1 and DMT1 protein and mRNA expressions were increased in BV-2 cells in the 10, 20, 40 μmol·L−1 lead acetate groups (P<0.05), especially in the 40 μmol·L−1 lead acetate group; the FPN1 protein expression did not change significantly, but the FPN1 mRNA expressions in BV-2 cells in the 10, 20, 40 μmol·L−1 lead acetate groups were significantly decreased (P<0.05). Compared with the control group, the intracellular GSH level decreased and the lipid ROS content increased in all three lead acetate groups; compared with the 40 μmol·L−1 lead acetate group, the GSH level increased by 12.30% and the lipid ROS content decreased by 13.00% in the 40+DFO group (P<0.05). The expressions of GPX4 protein were reduced to 50.00%, 35.00%, and 17.00% of that of the control group in the 10, 20, and 40 μmol·L−1 lead acetate groups respectively, while the expressions of GPX4 mRNA were also significantly reduced; the expressions of SLC7A11 protein and mRNA in the 20 and 40 μmol·L−1 lead acetate groups were lower than that in the control group, with the most significant decrease in the 40 μmol·L−1 lead acetate group (P<0.05). Conclusion Lead exposure could induce ferroptosis in BV-2 cells, in which iron transport imbalance and oxidative damage might be involved.