Textual Research on Principle of Dose Conversion in Ancient Famous Classical Formulas / 中国实验方剂学杂志

Due to the difference between the system of weights and measures， and the dosage of clinical prescriptions of traditional Chinese medicine in various historical periods， the dosage and conversion standard of prescriptions in past dynasties are different. Therefore， when discounting the dosage of famous classical formulas， the principles of inheriting the essence， making the past serve the present， linking the past and the present， and forming a consensus should be followed， firstly， the dosage of the prescription was converted according to the weights and measures system of the past dynasties. If the converted dosage significantly exceeds the provisions of the 2020 edition of Chinese Pharmacopoeia， then on the premise of ensuring that the proportion of the original prescription drug dosage remains unchanged， the conversion shall be based on expert consensus and drug safety evaluation. For drugs measured in non-standard units， a conversion range is provided based on comprehensive literature analysis and physical measurements. For the conversion of service volume， the original text was used as the basis for the conversion with reference to the measurement standards of different eras. If the original dosage is not clear， the converted dosage will be determined based on the historical evolution of the formula， referring to relevant ancient books， and combining modern applications. Eventually， the converting standard for famous classical formulas was determined as follows：during the Han and Tang dynasties， one Liang（两） was equivalent to 13.8 g and one Sheng（升） was equivalent to 200 mL， in the Tang dynasty， one Fen（分） was equivalent to 3.45 g， during the Song， Jin and Yuan dynasties， one Qian（钱） was equivalent to 4.13 g and one Zhan（盏） was equivalent to 300 mL， during the Ming and Qing dynasties， one Qian（钱） was equivalent to 3.73 g， and one Bei（杯） and one Zhong（盅） were equivalent to 200 mL. For drugs recorded in non-standard units of measurement， it is necessary to conduct actual measurements to determine their conversion standards based on comprehensive analysis to determine their origin. If necessary， different records of the dosage of drugs with the same or similar efficacy and indications in medical books of similar ages can be used to assist in determining the conversion standards. The analysis of the principle of dosage conversion for Chinese medicine is helpful for the clinical application and development of famous classical formulas.

Effect of LncRNA p21 regulating Hippo-YAP signaling pathway on formation of abdominal aortic aneurysm in mice and its mechanism / 中国药理学通报

Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE

Clinical follow-up study of SARS-CoV-2 Omicron infection / 上海预防医学

ObjectiveTo observe the clinical course and explore the risk factors for SARS-CoV-2 RNA negative conversion duration （NCD） in asymptomatic and mild-symptomatic patients infected with the SARS-CoV-2 Omicron variant. MethodsClinical data were collected from 244 confirmed cases of corona virus disease （COVID-19） with Omicron variant infection admitted to a temporal makeshift hospital in Shanghai from April 9， 2022 to May 20， 2022. Demographic and clinical data were analyzed， with a primary focus on the time of COVID-19 nucleic acid conversion. Univariate and multivariate Cox regression analysis were used to determine identify risk factors associated with NCD. ResultsThe median duration of negative RNA conversion was 9 days （ranged 7‒12 days）. The percentage of patients with positive nucleic acid results on the 5th， 7th， 10th， and 14th days after confirmed infection was 68.4%， 47.1%， 20.1%， and 5.7%， respectively. Kaplan-Meier curves indicated a median nucleic acid conversion time of 12 days （ranged 10‒14 days） for patients with hypertension， 9 days （ranged 7‒11 days） in patients without hypertension， and 11 days （ranged 9‒13 days） for patients aged ≥60 years， and 9 days （ranged 7‒11 days） for patients aged <60 years. Multivariate Cox regression analysis showed that only hypertension was an independent risk factor of NCD （RR=1.60； 95% CI： 1.03‒2.49， P=0.036）. ConclusionIn asymptomatic or mildly symptomatic patients infected with the Omicron variant， 20.1% patients continue to exhibit positive viral nucleic acid on the 10th days of infection. The independent risk factor associated with the conversion of SARS-CoV-2 nucleic acid to negative is hypertension.

Usage and Dosage Analysis and Countermeasures for Development of Compound Preparations of Han Dynasty Famous Classical Formulas / 中国实验方剂学杂志

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

Effects and mechanism of veratramine on the proliferation of human glioblastoma U251 cells / 中国药房

OBJECTIVE To explore the effects and potential mechanism of veratramine （VTM） on the proliferation of human glioblastoma U251 cells. METHODS The network pharmacology methods were adopted to screen the targets of ferroptosis related to the effects of VTM on glioblastoma， and to conduct gene ontology and Kyoto Encyclopedia of Genes and Genosomes enrichment analysis. Using U251 cells as the object， CCK-8 assay， the observation of cell morphological changes， DCFH-DA fluorescence probe method， FerroOrange fluorescence probe method and Western blot assay were used to validate the inhibitory effects of VTM on U251 cell proliferation and its possible mechanism. RESULTS Totally 462 targets of ferroptosis related to the effects of VTM on glioblastoma were screened out； they mainly enriched in biological processes such as oxidative stress and apoptosis， and cellular components such as cytoplasmic vesicles and mitochondrial membranes； they affected molecular functions such as iron ion （Fe2+） binding and DNA transcription processes， as well as iron death and phosphoinositide 3-kinase/protein kinase B signaling pathways. VTM with 40， 60， 80， 100， 120 and 140 μmol/L could significantly reduce the cell survival rate （P＜ 0.01）； VTM with 40， 80 and 120 μmol/L could cause cell atrophy and nuclear fragmentation， significantly inhibit the clone formation， increase the levels of intracellular reactive oxygen species （ROS） and Fe2+ levels， increase the expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） protein to different extents， while down-regulate the expression of glutathione peroxidase 4 （GPX4） protein （P＜0.05 or P＜0.01）. CONCLUSIONS VTM can inhibit the proliferation of U251 cells， and promote the accumulation of intracellular ROS and Fe2+， thus inducing ferroptosis； its mechanism might be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Analysis of immune microenvironment and potential sensitive drugs in esophageal squamous cell carcinoma based on GEO database and bioinformatics method / 中国胸心血管外科临床杂志

@#Objective    To construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods     The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. Results    A total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion     A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.

Research progress of medication treatment of dry age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is one of the leading causes of irreversible visual impairment worldwide, and the number of patients is increasing with the aging of the population, with dry ARMD accounting for about 90% of cases. Effective treatments for dry ARMD are currently lacking, making it a prominent area of research. Pharmacotherapy, targeting pathogenic factors such as oxidative damage, inflammation, and vascular issues contributing to ARMD, is one of the main treatments and some drugs have been shown to slow the progression of ARMD. This article reviews drug treatments for dry ARMD, including antioxidant drugs, complement biological agents, non-steroidal anti-inflammatory drugs and immunosuppressants, vasodilators, neurotrophic drugs, as well as traditional Chinese medicine. It summarizes their mechanisms and recent clinical research to contribute valuable insights for the treatment of dry ARMD and the development of novel therapeutic agents.

Clinical value of a cuproptosis-related differential long non-coding RNA scoring formula in clear cell renal cell carcinoma / 肿瘤研究与临床

Objective:To investigate the value of a cuproptosis-related differential long non-coding RNA (lncRNA) scoring formula related to the prognosis of clear cell renal cell carcinoma (ccRCC) patients in the clinical diagnosis, prognosis prediction and treatment options based on bioinformatics.Methods:Gene matrix and clinical data of ccRCC patients were obtained from the Cancer Genome Atlas (TCGA) database (update to 29 March, 2022). The expression data of 539 ccRCC tissues and 72 paracancerous normal tissues were collected from gene matrix; the data of 530 ccRCC were collected from clinical data. Pearson correlation analysis, Wilcoxon signed rank test and univariate Cox proportional risk model were used to analyze the screened cuproptosis-related differential lncRNA related to the prognosis. R software was used to randomly divide 530 ccRCC patients with survival data into training set (266 cases) and validation set (264 cases) according to approximate 1∶1 ratio. LASSO regression analysis was used to construct a cuproptosis-related differential lncRNA scoring formula and cross-validation was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the specificity and sensitivity of cuproptosis-related differential lncRNA scoring formula, and the area of the curve (AUC) was calculated. According to the median risk value, all patients were divided into the low-risk group and high-risk group; Kaplan-Meier method was used to analyze the difference in the overall survival (OS) of patients in the low-risk group and high-risk group. T test was used to detect the differences in the risk value of patients with different clinicopathological characteristics. R package rms was used to construct the nomogram for predicting 1-year, 3-year, 5-year OS rates of ccRCC patients, R package pRRophetic was used to predict the half-inhibitory concentration ( IC50) of common targeted drugs such as sorafenib and sunitinib in clinical treatment of ccRCC patients, and IC50 value of patients in low-risk group and high-risk group was compared by using Wilcoxon signed rank test. Tissue samples of 20 ccRCC patients who underwent radical nephrectomy and were diagnosed with pathology and the matched paracancerous normal tissues were collected from the First Hospital of Shanxi Medical University between June 2021 and December 2021. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of key lncRNA in ccRCC tissues. Results:Based on the expression matrix of 10 cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, CDKN2A) of ccRCC patients in TCGA database, 153 cuproptosis-related differential lncRNA related to the prognosis were identified. According to LASSO regression analysis, a scoring formula of 4 cuproptosis-related differential lncRNA related to the prognosis was obtained, risk value was calculated as 0.020×AC015912.3+0.011×AC026401.3+0.063×AC103706.1+(-0.076)×EPB41L4A-DT. All patients were divided into high-risk group (≥0.76) and low-risk group (<0.76) based on the median value (0.76). ROC curve analysis showed that the scoring formula had good prediction accuracy in 1-year, 3-year, 5-year OS rates. In training set, validation set, the total cohort, the OS of patients in the high-risk group was worse than that in the low-risk group (all P < 0.001). The age, pathological degree, tumor staging, risk value calculated by cuproptosis-related differential lncRNA were independent influencing factors of OS (all P < 0.001). There were statistically significant differences in the risk value calculated by cuproptosis-related differential lncRNA scoring formula among patients with different pathological degree, tumor staging, T staging, N staging, M staging (all P < 0.01), while there were no statistically significant differences among patients with different gender and age (all P > 0.05). The established nomogram had good prediction accuracy in the 1-year, 3-year, 5-year OS rates. Sunitinib and sirolimus showed higher sensitivity in the high-risk group; axitinib, sorafenib and pazopanib showed higher sensitivity in the low-risk group. qRT-PCR results showed that relative expression level of AC015912.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.68±0.24, t = 6.37, P < 0.01); the relative expression level of AC026401.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.05 vs. 0.64±0.22, t = 7.29, P < 0.01); the relative expression level of AC103706.1 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.64±0.21, t = 7.49, P < 0.01); the relative expression level of EPB41L4A-DT in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.06 vs. 0.73±0.10, t = 10.68, P < 0.01). Conclusions:Cuproptosis-related differential lncRNA scoring formula based on TCGA database can be used as a new marker for clinical diagnosis and prognosis prediction of ccRCC patients, which can help guide the clinical drug treatment of patients and facilitate accurate diagnosis and treatment.

Identification and study of regulatory axis that miRNA-224-5p targets NEDD4L gene in clear cell renal cell carcinoma / 肿瘤研究与临床

Objective:To screen key genes of renal clear cell carcinoma based on bioinformatics methods, identify possible microRNA (miRNA)-mRNA action axis, and explore the expression of related genes in clear cell renal cell carcinoma tissues and cells.Methods:Gene expression profiles of GSE40435 and GSE71302 datasets were obtained from the Gene Expression Omnibus (GEO) database. TCGA-KIRC datasets were obtained from The Cancer Genome Atlas (TCGA) database. R software was used to identify the differentially expressed mRNA and miRNA, and the functional enrichment analysis was performed. STRING database and Cytoscape software were used to perform the protein interaction analysis. The prognosis-related differentially expressed miRNA was evaluated by the Oncomir database. The potential targeted genes regulated by miRNA were determined by using TargetScan and miRDB targeted gene prediction tools. The tissue samples and clinicopathological features of 34 patients with clear cell renal cell carcinoma in the First Hospital of Shanxi Medical University from June to December 2021 were collected, and normal renal cell line 293T and clear cell renal cell carcinoma cell line 786O were selected. The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), was used to detect the relative expression of genes; Western blotting and immunohistochemical staining were used to detect the expression levels of the targeted proteins. The dual luciferase reporter gene assay was carried out to verify the targeting relationship between genes.Results:A total of 1 351 differentially expressed mRNA and 50 differentially expressed miRNA were screened and identified. The result of functional enrichment analysis suggested that the fatty acid metabolism pathway and xenobiotic metabolism pathway were suppressed in clear cell renal cell carcinoma, while the apoptosis and immune response pathways were activated. Protein interaction analysis suggested that the signal transduction and protein ubiquitination pathways might play a key role in clear cell renal cell carcinoma. The screening results showed that miRNA-224-5p (miR-224-5p) was most closely associated with clear cell renal cell carcinoma progression and was highly expressed in tumor tissues, and its prognosis-related target gene was NEDD4L. The relative expression of NEDD4L mRNA in clear cell renal cell carcinoma tissues and paraneoplastic tissues were 0.138±0.103 and 1.000±0.026 ( t = 46.23, P < 0.05), and the relative expression of miR-224-5p was 1.000±0.043 and 0.129±0.108 ( t = 45.28, P < 0.05). The differences of NEDD4L mRNA and miR-224-5p expressions in different grades and stages of clear cell renal cell carcinoma tissues were statistically significant (all P < 0.05). The expression of NEDD4L protein was decreased in clear cell renal cell carcinoma. The relative expression of NEDD4L gene in 293T and 786O cells were 1.000±0.125 and 0.210±0.044 ( t = 17.52, P < 0.05); the relative expressions of miR-224-5p gene were 0.209±0.049 and 1.000±0.234 ( t = 10.61, P < 0.05). The relative expressions of NEDD4L mRNA in miRNA mimic group and negative control group were 0.236±0.062 and 1.000±0.024, and the difference was statistically significant ( t = 43.56, P < 0.05). NEDD4L protein expression was reduced in the miRNA mimic group. Dual luciferase reporter gene assay suggested that NEDD4L was a direct target gene of miR-224-5p. Conclusions:In clear cell renal cell carcinoma, miR-224-5p targets and regulates NEDD4L expression, and this mechanism may be related to carcinogenesis and progression of clear cell renal cell carcinoma.

Establishment and operation of international English journal in special medicine / 中国辐射卫生

In response to the national strategy of building first-class journals and filling the gaps in English journals on radiation medicine and protection, the Radiation Medicine and Protection (RMP) was founded. Within three years, it has entered domestic and international databases such as DOAJ, Scopus, CSCD, WJCI and Embase with its CiteScore ranking first in the discipline and WJCI index surpassing a variety of international authoritative radiation protection journals. Collaborating with KeAi and Elsevier successively, this open access publisher has gained a significant number of international citations to achieve international visibility. Owing to the influence of disciplinary characteristics, domestic evaluation systems, and international exchange situation, RMP is facing development bottlenecks. We hope to explore breakthrough measures from the aspects of expanding manuscript sources, strengthening academic exchanges, and attracting young experts to joining the editorial board.

Application of ulnar nerve diameter changes examined by HRUS in patients with cubital tunnel syndrome / 中国骨伤

OBJECTIVE@#To evaluate the value of high-resolution ultrasound the diagnosis and prognosis of cubital tunnel syndrome.@*METHODS@#From January 2018 to June 2019, 47 patients with cubital tunnel syndrome were treated with ulnar nerve release and anterior subcutaneous transposition. There were 41 males and 6 females, aged from 27 to 73 years old. There were 31 cases on the right, 15 cases on the left, and 1 case on both sides. The diameter of ulnar nerve was measured by high-resolution ultrasound pre-and post-operatively, and measured directly during the operation. The recovery status of the patients was evaluated by the trial standard of ulnar nerve function assessment, and the satisfaction of the patients was assessed.@*RESULTS@#All the 47 cases were followed up for an average of 12 months and the incisions healed well. The diameter of ulnar nerve at the compression level was (0.16±0.04) cm pre-operatively, and the diameter of ulnar nerve was (0.23±0.04) cm post-operatively. The evaluation of ulnar nerve function:excellent in 16 cases, good in 18 cases and fair in 13 cases. Twelve months post-operatively, 28 patients were satisfied, 10 patients were general and 9 patients were dissatisfied.@*CONCLUSION@#The preoperative examination of ulnar nerve by high-resolution ultrasound is consistent with the intuitive measurement during operation, and the result of postoperative examination of ulnar nerve by high-resolution ultrasound is consistent with follow-up results. High-resolution ultrasound is an effective auxiliary method for the diagnosis and treatment of cubital tunnel syndrome.

Analysis of the vaccination status of enterovirus type 71 inactivated vaccine in China from 2017 to 2021 / 中华流行病学杂志

Objective: To understand the vaccination status of enterovirus type 71 (EV71) inactivated vaccines in China from 2017 to 2021 and provide evidence for making policy on immunization strategy against hand, foot and mouth disease (HFMD). Methods: Using the reported dose number of EV71 vaccination and birth cohort population data collected by the China immunizaiton program information system to estimate the cumulative coverage of EV71 vaccine by the end of 2021 among the birth cohorts since 2012 at national, provincial, and prefecture levels, and analyze the correlation between the vaccination coverage and the potential influencing factors. Results: As of 2021, the estimated cumulative vaccination coverage of the EV71 vaccine was 24.96% in birth cohorts since 2012. The cumulative vaccination coverage was between 3.09% and 56.59% in different provinces, between 0 and 88.17% in different prefectures. There was a statistically significant correlation between vaccination coverage in different regions and the region's previous HFMD prevalence and disposable income per capita. Conclusions: Since 2017, the EV71 vaccines have been widely used nationwide, but the coverage of EV71 vaccination varies greatly among regions. Vaccination coverage is higher in relatively developed regions, and the intensity of previous epidemic of HFMD may have a certain impact on the acceptance of the vaccine and the pattern of immunization service. The impact of EV71 vaccination on the epidemic of HFMD requires further studies.

A glass micropipette vacuum technique of cerebrospinal fluid sampling in C57BL/6 mice / 生理学报

The purpose of this study was to establish a suitable method for extracting cerebrospinal fluid (CSF) from C57BL/6 mice. A patch clamp electrode puller was used to draw a glass micropipette, and a brain stereotaxic device was used to fix the mouse's head at an angle of 135° from the body. Under a stereoscopic microscope, the skin and muscle tissue on the back of the mouse's head were separated, and the dura mater at the cerebellomedullary cistern was exposed. The glass micropipette (with an angle of 20° to 30° from the dura mater) was used to puncture at a point 1 mm inboard of Y-shaped dorsal vertebral artery for CSF sampling. After the first extraction, the glass micropipette was connected with a 1 mL sterile syringe to form a negative pressure device for the second extraction. The results showed that the successful rate of CSF extraction was 83.33% (30/36). Average CSF extraction amount was (7.16 ± 0.43) μL per mouse. In addition, C57BL/6 mice were given intranasally ferric ammonium citrate (FAC) to establish a model of brain iron accumulation, and the CSF extraction technique established in the present study was used for sampling. The results showed that iron content in the CSF from the normal saline control group was not detected, while the iron content in the CSF from FAC-treated group was (76.24 ± 38.53) μmol/L, and the difference was significant. These results suggest that glass micropipette vacuum technique of CSF sampling established in the present study has the advantages of simplicity, high success rate, large extraction volume, and low bleeding rate, and is suitable for the research on C57BL/6 mouse neurological disease models.

Analysis of the progress of clinical trials for ophthalmic drug in China, 2022 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P&#x003E;0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.

Establishment and preliminary application of organoids in ovarian cancer / 中华妇产科杂志

Objective:To explore the establishment and application of ovarian cancer organoids.Methods:Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50) in different organoids. Results:(1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t=3.429, P=0.022]. Conclusions:Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.

Arthroscopic modified Brostr?m procedure combined with peroneal tendon debridement in the treatment of chronic lateral ankle instability concomitant with fibular tendinitis / 中华创伤杂志

Objective:To compare the efficacies of arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement in the treatment of chronic lateral ankle instability (CLAI) concomitant with fibular tendinitis.Methods:A retrospective cohort analysis was conducted on the clinical data of 31 patients with CLAI concomitant with fibular tendinitis, who were treated in Beijing Tongren Hospital, Capital Medical University between March 2019 and December 2021. The patients included 17 males and 14 females, aged 16-57 years [(32.8±9.6)years]. The anterior drawer test and talar tilt test were positive in all patients preoperatively. Diagnosis was confirmed by physical examination and MRI, and calcaneofibular ligament rupture was excluded. Eleven patients received arthroscopic modified Brostr?m procedure combined with peroneal tendon debridement (modified Brostr?m procedure+tendon debridement group), and 20 underwent pure arthroscopic modified Brostr?m procedure (modified Brostr?m procedure group). The operation time, intraoperative blood loss and length of hospital stay were documented. The visual analogue score (VAS) in peroneal tendon area was assessed before operation and at postoperative 2, 6 and 12 weeks. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and foot and ankle outcome score (FAOS) were assessed before operation and at postoperative 6 and 12 weeks. The anterior drawer test was performed at the last follow-up. The foot and ankle ability measure (FAAM) score was assessed before operation and at the last follow-up. Postoperative wound healing and complications were also observed.Results:All the patients were followed up for 4-19 months [(11.3±3.5)months]. The operation time was (66.0±4.2)minutes in the modified Brostr?m procedure+tendon debridement group, which was significantly longer than (61.5±3.4)minutes in the modified Brostr?m procedure group ( P<0.05). There was no significant difference in intraoperative blood loss or length of hospital stay between the two groups (all P>0.05). Compared with the preoperation, the value of VAS was significantly lowered, and the values of AOFAS ankle-hindfoot score, FAOS and FAAM score were significantly increased at different postoperative timepoints (all P<0.01). No significant differences in the values of VAS, AOFAS ankle-hindfoot score, FAOS or FAAM score were seen between the two groups before operation (all P>0.05). The value of VAS was 3.0(3.0, 4.0) points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 4.0(4.0, 4.0)points in the modified Brostr?m procedure group at 2 weeks postoperatively ( P<0.05). The value of VAS was 2.0(1.0, 3.0)points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 3.0(2.3, 3.0)points in the modified Brostr?m procedure group at 6 weeks postoperatively ( P<0.05). At 12 weeks postoperatively, there was no significant difference in the value of VAS between the two groups ( P>0.05). There were no significant differences in the values of AOFAS ankle-hindfoot score and FAOS between the two groups at 6 or 12 weeks postoperatively (all P>0.05). The anterior drawer test was negative in all patients at the last follow-up. No significant difference was seen in the value of FAAM score between the two groups at the last follow-up ( P>0.05). All incisions were healed well in the first stage after operation, without the occurrence of joint infection, impaired joint motion, nerve injury or deep vein thrombosis. Conclusions:Arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement can both improve the foot function in CLAI patients concomitant with fibular tendinitis. However, the combined treatment allows for early pain relief, without increasing the risk of complications, and can therefore contribute to a faster postoperative recovery.

Efficacy and safety of dual drug regimen in patients with hantavirus hemorrhagic fever with renal syndrome and upper gastrointestinal bleeding / 中国医师杂志

Objective:To explore the efficacy and safety of dual drug regimen in the treatment of Hantavirus hemorrhagic fever with renal syndrome with upper gastrointestinal bleeding.Methods:Sixty patients with hantavirus hemorrhagic fever with renal syndrome and upper gastrointestinal bleeding admitted to the Eighth Medical Center of the 301 Hospital from January 2020 to January 2022 were selected as the research objects. They were randomly divided into the control group (30 cases) and the observation group (30 cases). They were treated with omeprazole and omeprazole combined with octreotide respectively for 72 hours. The clinical efficacy, hemostasis time, hospital stay, hemoglobin, serum glucagon levels, adverse reactions and rebleeding rate were compared between the two groups.Results:The total effective rate of clinical treatment in the observation group was 93.33%(28/30), significantly better than 76.67%(23/30) in the control group, with a statistically significant difference ( P<0.05). The hemostasis time and hospitalization time in the observation group were significantly shorter than those in the control group (all P<0.05). After treatment, the hemoglobin level in both groups was higher than that before treatment, and the serum glucagon level was lower than that before treatment, the difference was statistically significant (all P<0.05); After treatment, the hemoglobin level in the observation group was higher than that in the control group, and the serum glucagon level was lower than that in the control group (all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (all P>0.05). The 48 hour rebleeding rate in the observation group was 3.33%(1/30), lower than the 26.67%(8/30) in the control group, with a statistically significant difference ( P<0.05). Conclusions:The dual drug regimen for Hantavirus hemorrhagic fever with renal syndrome with upper gastrointestinal bleeding can effectively control the bleeding symptoms, improve the hemostasis effect, lower the serum glucagon level, reduce the risk of rebleeding, and its safety is worthy of recognition.

Comparison of 3D-arterial spin labeling and digital subtraction angiography in the diagnosis of occlusion and collateral circulation in patients with acute ischemic stroke / 中国医师杂志

Objective:To explore the diagnostic value of 3D-arterial spin labeling (ASL) and digital subtraction angiography (DSA) in the occlusion and collateral circulation (CC) of patients with acute ischemic stroke (AIS).Methods:From January 2019 to June 2020, 53 cases of AIS patients with middle cerebral artery (MCA) occlusion in Langfang Hospital of Traditional Chinese Medicine were selected as the research objects. All patients underwent DSA and 3D ASL examination. According to the gold standard of DSA, the diagnostic value of proximal intra-arterial signal (IAS) in 3D-ASL was observed, and the clinical value of distal IAS in the diagnosis of lateral CC was observed. Univariate and multivariate logistic regression were used to identify risk factors for poor outcome in AIS patients.Results:There were 31 cases with good collateral circulation judged by DSA. Taking DSA as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of digital IAS in diagnosing CC status were 93.55%, 81.82%, 87.88%, 90.00% and 88.68%, respectively. The National Institutes of Health Stroke Scale (NIHSS) score of patients with good CC assessed by 3D-ASL was lower than that of patients with poor CC at admission, and the good prognosis rate at discharge was higher than that of patients with poor CC, with statistically significant difference (all P<0.05). There was no significant difference in clinical data between patients with good CC and those with poor CC, such as gender, age, history of atrial fibrillation, hypertension, diabetes, smoking, drinking, onset to treatment time, treatment methods, etc (all P>0.05). Univariate and multivariate analysis showed that poor CC assessed by ASL was a risk factor for poor prognosis in AIS patients ( OR=5.897, P<0.05). Conclusions:The proximal and distal IAS of 3D-ASL can provide important diagnostic clues for detecting arterial occlusion and collateral perfusion in patients with AIS, and the detection of CC by ASL is of great value for prognosis.

Relationship between self-perceptions of aging and cognitive function in community elderly: the mediating and moderating effects of loneliness / 中华行为医学与脑科学杂志

Objective:To explore the relationship between self-perceptions of aging and cognitive function, and the mediating and moderating effect of loneliness among them.Methods:A multi-stage stratified sampling was conducted in Jinzhou from September to November 2021, and 318 community-based elderly were included.General data questionnaire, the brief ageing perceptions questionnaire (BAPQ), UCLA loneliness scale(UCLA-LS) and mini-mental state examination (MMSE) were applied to all subjects.IBM SPSS 25.0 software was used to conduct independent sample t-test, analysis of variance and Pearson correlation analysis, and Bootstrap program of AMOS 22.0 was used to analyze the mediation effect.The model in SPSSAU on-line analysis program was used to test the moderating effect. Results:The average scores of self-perceptions of aging, loneliness and cognitive function were (44.85±12.48), (41.70±8.73) and (24.87±3.40) respectively.And 65 of 318 subjects had cognitive impairment, and the detection rate was 20.44%(65/318). Self-perceptions of aging, loneliness and cognitive function scores were significantly correlated between each other(all P<0.05). Self-perceptions of aging had a negative effect on cognitive function ( β=-0.467, P<0.01). Self-perceptions of aging had a positive effect on loneliness ( β=0.585, P<0.01). Loneliness had a negative effect on cognitive function ( β=-0.234, P<0.01). The indirect standardization effect of loneliness between self-perceptions of aging and cognitive function was -0.137, and the mediating effect accounted for 22.68% of the total effect.Loneliness played a moderating role between self-perceptions of aging and cognitive function ( β=-0.114, t=-2.26, P=0.025). Conclusion:Self-perceptions of aging and loneliness can predict the cognitive function in the elderly, and loneliness plays a mediating role between self-perceptions of aging and cognitive function.Early detection of negative senility emotion and loneliness of the elderly will play a positive role in preventing the occurrence of cognitive impairment.

Efficacy of liraglutide combined with metformin in the treatment of type 2 diabetes mellitus in 60 overweight or obese patients / 中国基层医药

Objective:To investigate the clinical efficacy of liraglutide combined with metformin in the treatment of type 2 diabetes mellitus in overweight or obese patients.Methods:The clinical data of 120 overweight or obese patients with type 2 diabetes mellitus admitted to Bayannur Hospital from January 2020 to June 2021 was retrospectively analyzed. They were divided into study and control groups ( n = 60/group) according to different treatments. The study group was treated with liraglutide combined with metformin, and the control group was treated with metformin alone. All patients were treated for 12 weeks. Clinical efficacy was compared between the two groups. Results:After treatment, body mass, body mass index, fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, visceral fat area, and insulin resistance index in the study group were (71.51 ± 10.12) kg, (25.98 ± 2.63) kg/m 2, (6.09 ± 0.99) mmol/L, (9.08 ± 2.39) mmol/L, (6.75 ± 1.13)%, (4.43 ± 0.88) mmol/L, (1.76 ± 0.68) mmol/L, (2.29 ± 0.90) mmol/L, (108.21 ± 26.46) cm 2 and (3.57 ± 1.45), respectively, which were significantly lower than (75.57 ± 7.11) kg, (27.91 ± 2.46) kg/m 2, (7.02 ± 0.95) mmol/L, (11.26 ± 2.86) mmol/L, (7.28 ± 1.04)%, (5.24 ± 1.11) mmol/L, (2.19 ± 0.70) mmol/L, (2.86 ± 0.97) mmol/L, (118.32 ± 28.63) cm 2, and (4.28 ± 2.07) respectively in the control group ( t = 2.54, 4.15, 5.23, 4.53, 2.66, 4.45, 3.43, 3.39, 2.01, 2.19, all P < 0.05). High-density lipoprotein cholesterol in the study group was significantly higher than that in the control group [(1.55 ± 0.28) mmol/L vs. (1.20 ± 0.32) mmol/L, t = -6.38, P < 0.05]. The grade of nonalcoholic fatty liver disease in the study group was significantly superior to that in the control group ( Z =-2.16, P < 0.05). Conclusion:Liraglutide combined with metformin can effectively improve blood glucose and lipid levels, and reduce insulin resistance, body weight, visceral adipose tissue and liver hepatocellular fatty deposits in overweight or obese patients with type 2 diabetes mellitus.