Aim To investigate the protective effect of Jujing formula on retina of mice with dry age-related macular degeneration(AMD).Methods The mouse model of dry AMD was induced by intraperitoneal in-jection of sodium iodate,and the prognosis was given to the Jujing formula.Retinal thickness was detected by optical coherence tomography(OCT),the retinal morphological changes were observed by hematoxylin-eosin(HE)staining,and the apoptosis of retinal cells was detected by in situ terminal transferase labeling(TUNEL)staining.Combination of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1 β)in eyeballs and serum,superoxide dis-mutase(SOD),glutathione(GSH)and malondialde-hyde(MDA)were evaluated to assess the protective effects of Jujing formula on retinal injury in mice with dry AMD.Results The results of OCT,HE and TUNEL staining showed that Jujing formula significant-ly improved the retinal injury induced by sodium iodate in mice with dry AMD,increased the retinal thickness(P＜0.05),reduced the apoptosis of retinal cells(P＜0.01),and increased the levels of GSH,IL-6 and SOD activity in eyeballs and serum(P＜0.01).The levels of TNF-α,IL-6,IL-1β and MDA were reduced(P＜0.01).Conclusions Jujing formula has certain therapeutic effects on retinal injury in dry AMD,which may be related to inhibiting inflammatory response and enhancing antioxidant capacity.

Endocrine therapy is the most important adjuvant treatment for early estrogen receptor(ER)-positive breast cancer.ER-low-positive(immunohistochemistry staining 1%-10%)breast cancer has drawn widespread attention in recent years.This group accounts for 3%-9%of overall breast cancer patients.The efficacy of endocrine adjuvant therapy is relatively limited in patients with ER-low-positive breast cancer.Although the proportion of patients with low ER expression in breast cancer population is relatively low,the clinical needs of this population can not be ignored because of the large number of breast cancer patients.A number of studies have suggested that ER-low-positive breast cancer is different from ER-positive breast cancer,and is similar to ER-negative breast cancer in terms of molecular and biological characteristics,clinical features and prognosis.There are still controversies on the benefit and duration of endocrine therapy for early ER-low-positive breast cancer,and there is a lack of evidence from large-scale prospective studies.Multiple retrospective studies and meta-analyses have suggested that ER-low-positive breast cancer may have limited benefit from adjuvant endocrine therapy,and therefore endocrine therapy should be considered with caution in this population.The benefit of adjuvant therapy combined with cyclin-dependent kinase(CDK)4/6 inhibitors is yet to be supported by future data.Some patients with ER-low-positive breast cancer may try adjuvant chemotherapy in consideration of other risk factors.Additionally,clinical trials that test antibody-drug conjugates(such as sacituzumab govitecan and Dato-DXd),poly(ADP-ribose)polymerase(PARP)inhibitors,and immunotherapies for the treatment of early ER-low-positive breast cancer are still ongoing,including the phase Ⅲ ASCENT-05 study evaluating the adjuvant therapy of sacituzumab govitecan combined with pembrolizumab in high-risk human epidermal growth factor receptor 2(HER2)-negative,ER and progesterone receptor(PR)＜10%patients after surgery,the phase Ⅲ SASCIA study evaluating the adjuvant therapy of sacituzumab govitecan in high-risk HER2-negative patients after surgery,and the phase Ⅲ TROPION-Breast 04 study evaluating the neoadjuvant therapy of Dato-DXd combined with durvalumab.In addition,a neoadjuvant treatment for triple-negative breast cancer(TNBC)and ER-low expression breast cancer with olaparib and durvalumab(NCT03594396)is being explored,and the results are worth expecting.This article aimed to introduce the definition,clinical and pathological characteristics,and prognosis of ER-low breast cancer,and expound on the current treatment status and potential therapeutic strategies for HER2-negative,ER-low-positive early breast cancer in the future.

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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the efficacy of different types of neoadjuvant therapy for esophageal cancer.Methods:The clinical data of 542 patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant therapy in Anyang Tumor Hospital of Science and Technology from January 2015 to May 2022 were retrospectively analyzed. These patients, consisting of 198 females and 344 males, with 289 cases aging ≤ 65 and 253 cases aging >65, were divided into a neoadjuvant chemoradiotherapy (NCRT) group (137 cases), a neoadjuvant chemotherapy (NCT) group (241 cases), and a neoadjuvant immunotherapy plus chemotherapy (NICT) group (164 cases). In this study, primary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, and secondary endpoints comprised overall survival (OS), progression-free survival (PFS), and safety. Survival analysis was performed using the Kaplan-Meier method, and inter-group comparisons were made using the Log-rank test. Furthermore, prognostic factors were analyzed based on the Cox proportional hazards regression model.Results:The NCRT, NCT, and NICT groups exhibited MPR and pCR rates of 66.4% (91/137) and 35.3% (85/241), 63.4% (104/164) and 35.8% (49/137), and 6.6% (16/241) and 31.1% (51/164), respectively ( χ2=1.67, P < 0.001). These groups displayed 1-, 2-, and 3-year OS rates of 89.8%, 85.9%, and 91.9%; 82.3%, 71.4%, and 81.5%; and 72.3%, 61.4%, and 77.8%, respectively, with significant differences ( χ2=9.20, P < 0.01). Furthermore, they exhibited 1-, 2-, and 3-year PFS rates of 81.5%, 75.9%, and 80.1%; 67.9%, 61.0%, and 65.5%; and 66.6%, 53.5%, and 65.3%, respectively, with significant differences ( χ2=4.62, P < 0.05). Multivariate analysis showed that therapeutic modality, T stage, and N stage were independent prognostic factors for OS ( P < 0.05). Additionally, there was no difference in adverse reactions and postoperative complications among the three groups. Conclusions:Compared to NCT, NICT and NCRT feature higher pCR and MPR rates, along with more survival benefits. Therefore, neoadjuvant immunotherapy has the potential to serve as a preoperative therapeutic modality for esophageal cancer, yet large-scale randomized controlled trials are still required for confirmation.

Objective:To evaluate the efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC).Methods:A retrospective analysis was conducted on the data of 75 patients with R/M ESCC treated with sintilimab at Anyang Tumor Hospital from January 2020 to October 2021. The patients were divided into the radiotherapy (RT) group ( n=37) and non-radiotherapy (NRT) group ( n=38) based on whether they received radiotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse effects were compared between two groups. Count data were expressed as composition ratios and analyzed using Chi-square test or Fisher's exact test. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:There was no statistically significant difference in ORR and DCR between the RT and NRT groups (70% vs. 61%, P=0.375; 95% vs. 89%, P=0.414). However, the complete response (CR) rate in the RT group was higher compared to that in the NRT group (19% vs. 3%, P=0.022). The median follow-up duration was 25.4 months. There was no statistically significant difference in the median PFS and OS between the RT and NRT groups (13.8 months vs. 9.9 months, P=0.221; 20.2 months vs. 18.9 months, P=0.214). Subgroup analysis demonstrated that among patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes, there was no statistically significant difference in the median PFS between the RT and NRT groups (15.1 months vs. 8.4 months, P=0.115), but the median OS in the RT group was better than that in the NRT group (not reached vs. 12.3 months, P=0.036). Compared to the NRT group, besides an increase in grade 1-2 pneumonitis (41% vs. 18%, P=0.035), no significant increase in treatment-related toxicity was observed in the RT group. Conclusion:Immunotherapy combined with radiotherapy is safe in patients with R/M ESCC, and shows survival benefit in patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes.

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Objective:The sensory processing measure-preschool scale(SPM-P)was transformed into Chinese,and its re-liability and validity were tested in preschool children. Method:According to Brislin's translation model,the SPM-P source scale was translated into Chinese and the Chinese version of SPM-P scale was formed.From September 2021 to December 2021,395 preschool children were investigated by cluster stratified random sampling method to test the reliability and validity of the scale. Result:The Chinese version of the SPM-P scale includes 8 dimensions of social participation,vision,hear-ing,touch,body awareness,balance and movement,planning and conception,and overall sensory system,with a total of 75 items.Cronbach alpha coefficient for the overall scale was 0.899,the split half reliability coefficient was 0.700;the test-retest reliability coefficient was 0.899.The item content validity(I-CVI)value was 0.920,the average content validity(S-CVI/Ave)value was 0.984,and the content validity was good;the results of confirmatory factor analysis showed that the construct validity was good;The results of confirma-tory factor analysis showed that the construct validity was good(x2/df=2.41,CFI=0.992,TLI=0.960,RMSEA=0.060,SRMR=0.046);The Chinese version of SPM-P scale was negatively correlated with the corresponding evaluation dimensions of the screening questionnaire for children's sensory integration disorder,and the correla-tion coefficient was between-0.585 and-0.399,with good criterion validity. Conclusion:The Chinese version of SPM-P scale has good reliability and validity and can be used for stan-dardized evaluation of sensory integration ability of preschool children in China.

Objective:To study the effects of different calcium ion concentrations on epithelial mesenchymal transformation (EMT) of human peritoneal mesothelial cell (HPMC) via endoplasmic reticulum stress (ERS).Methods:HPMC cell line HMrSV5 was cultured in vitro and treated in groups. The cells in the control group, high calcium group 1, and high calcium group 2 were treated with medium containing calcium ion concentrations of 1.25, 1.75, and 2.25 mmol/L, respectively. The solvent control group was treated with medium containing 1.25 mmol/L physiological calcium ion concentration and 0.1% dimethyl sulfoxide (DMSO), the high calcium+solvent group was treated with medium containing 2.25 mmol/L calcium ion concentration and 0.1% DMSO, the high calcium+4-phenylbutyric acid (4-PBA) group was treated with medium containing 2.25 mmol/L calcium ion concentration and 1 mmol/L ERS inhibitor 4-PBA, and each group was treated for 48 hours. Morphological changes of cells in each group were observed under light microscope. The expressions of epithelial cell phenotype marker zonula occluden-1 (ZO-1) and mesenchymal cell phenotype marker α-smooth muscle actin (α-SMA) in the cells were observed by immunofluorescence staining. The expressions of EMT marker genes E-cadherin, ZO-1, α-SMA and Vimentin were detected by fluorescence quantitative polymerase chain reaction (PCR). The expressions of ERS marker proteins phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), transcription activating factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by Western blotting. Results:Compared with the control group, the morphology of HMrSV5 cells became slender and fibrotic, the fluorescence intensity of ZO-1 increased, and the fluorescence intensity of α-SMA decreased in high calcium 1 and high calcium 2 groups, indicating that the cells transformed from epithelial cells to mesenchyme cells. The mRNA expressions of E-cadherin and ZO-1 were significantly decreased, while the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly increased, moreover, the expressions of the above marker genes or proteins in the high calcium 2 group was more obvious than those in the high calcium 1 group [E-cadherin mRNA (2 -ΔΔCt): 0.53±0.05 vs. 0.75±0.09, ZO-1 mRNA (2 -ΔΔCt): 0.42±0.06 vs. 0.69±0.06, α-SMA mRNA (2 -ΔΔCt): 1.81±0.16 vs. 1.32±0.14, Vimentin mRNA (2 -ΔΔCt): 2.05±0.22 vs. 1.48±0.16, p-PERK protein (p-PERK/β-actin): 0.81±0.09 vs. 0.59±0.06, p-eIF2α protein (p-eIF2α/β-actin): 0.87±0.10 vs. 0.50±0.06, ATF4 protein (ATF4/β-actin): 0.93±0.10 vs. 0.72±0.06, CHOP protein (CHOP/β-actin): 0.79±0.09 vs. 0.46±0.04, all P < 0.05]. Compared with the solvent control group, the morphological changes of cells, the expressions of EMT marker genes and ERS marker proteins after high calcium ion concentration of 2.25 mmol/L were consistent with those in the high calcium 2 group than control group. Compared with the high calcium+solvent group, the cell morphology recovered the characteristics of polygonal and pebble-like epithelial cells in the high calcium+4-PBA group, the fluorescence intensity of ZO-1 increased, the fluorescence intensity of α-SMA decreased, and the mRNA expressions of E-cadherin and ZO-1 in the cells were significantly increased [E-cadherin mRNA (2 -ΔΔCt): 0.86±0.09 vs. 0.57±0.04, ZO-1 mRNA (2 -ΔΔCt): 0.81±0.06 vs. 0.48±0.05, both P < 0.05], the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly decreased [α-SMA mRNA (2 -ΔΔCt): 1.21±0.13 vs. 1.77±0.15, Vimentin mRNA (2 -ΔΔCt): 1.30±0.14 vs. 1.94±0.20, p-PERK protein (p-PERK/β-actin): 0.38±0.04 vs. 0.92±0.11, p-eIF2α protein (p-eIF2α/β-actin): 0.34±0.05 vs. 1.05±0.13, ATF4 protein (ATF4/β-actin): 0.57±0.06 vs. 0.97±0.11, CHOP protein (CHOP/β-actin): 0.51±0.04 vs. 0.90±0.12, all P < 0.05]. Conclusion:High calcium ion concentrations of 1.75 mmol/L and 2.25 mmol/L promote EMT of HPMC via activating ERS.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.