Preparing porcine lens to mimic human lens capsule.

PURPOSE: To develop a chemical method that makes porcine lens anterior capsule resemble human lens anterior capsule in tear force and perforating force. SETTING: Beijing Tongren Hospital, Beijing, China. DESIGN: Experimental study. METHODS: Porcine eyes were divided into groups, and reagents (0.9% physiological saline, 0.1% sodium hypochlorite, 0.3% sodium hypochlorite and 0.5% sodium hypochlorite) were injected into the anterior chamber respectively, recorded as groups A, B, C and D, respectively. A senior physician collected each group of anterior capsules after performing continuous circular capsulorhexis and assessing the anterior capsule's tearing and perforation forces.an additional group, which consisted of human lens anterior capsules taken in the operating room from cataract patients, recorded as group E. A tensile system was used to measure each sample's tensile force. RESULTS: A significant difference was found between group A and any other group in maximum tensile force and average tensile force both in transverse and longitudinal directions. No significant difference was found between any two groups from group B to group E. According to the surgeon's assessment, the tear force characteristic of the porcine lens anterior capsule treated with 0.1%, 0.3%, and 0.5% sodium hypochlorite solution was similar to that of the human lens anterior capsule. CONCLUSIONS: Porcine lens capsule treated using this method can be used for training of new surgeons. The porcine lens anterior capsule treated with 0.5% sodium hypochlorite, which results showed most resembled human lens anterior capsule, can be used for robotic training.

Case observation of viral keratitis caused by SARS-CoV-2 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To report three cases of viral keratitis caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).METHODS: Slit lamp, intraocular pressure, corneal fluorescence staining, anterior segment photography, in vivo confocal microscopy(IVCM), and routine fundus screening were performed in the three confirmed patients. Treatment involved Ganciclovir, artificial tears and glucocorticoid eye drops.RESULTS: Three patients with SARS-CoV-2 keratitis(SCK)recovered well after standard treatment.CONCLUSION: SARS-CoV-2 keratitis typically presents as corneal subepithelial infiltration and can result in a decrease in corneal subepithelial nerve fiber density and an increase in dendritic cells(DC). Antiviral therapy in combination with glucocorticoid has proven to be effective.

Blaps rynchopetera combined with cyclophosphamide affects proliferation and apoptosis of lung cancer cells via Wnt/β-catenin signaling pathway / 中国中药杂志

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/β-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and β-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.

Research progress on Huangqi Guizhi Wuwu Decoction and predictive analysis of quality markers / 中国中药杂志

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.

Dietary patterns of preschool children based on factor analysis combined with cluster / 公共卫生与预防医学

Objective To investigate the dietary intake of preschool children in Northwest China, and provide scientific basis for studying the dietary patterns and characteristics of preschool children and formulating targeted dietary interventions. Methods Using the self-designed “Semi-quantitative Food Frequency Questionnaire for Preschool Children in Northwest China“, a convenient sampling method was used to investigate the dietary intake of children aged 3 to 7 years in Northwest China. The factor analysis combined with the cluster method was used to extract the dietary pattern. Results Through factor analysis of the average daily food intake of preschool children, the results show that the KMO test value was 0.82, Bartlett’s test value was 4 528.97, and the associated probability was <0.001, so factor analysis can be performed. In order to obtain more typical factor components so that the results were easier to explain, under the guidance of nutrition experts, the first 4 common factors were finally retained for analysis, and the cumulative variance contribution rate was 62.17%. On this basis, the number of clusters was 4, and the K-means cluster analysis method was used to cluster the factor scores of various foods for preschool children. According to the proportions of various foods and the characteristics of the foods, The dietary patterns of preschool children can be divided into staple food-based dietary patterns, high-protein dietary patterns, healthy dietary patterns, and high-sugar dietary patterns. Conclusion Using factor analysis method, the scores of each food factor of preschool children were continuous variables, and the results were highly repeatable, and subsequent analysis can be carried out. The factor analysis combined with cluster analysis method extracting the dietary pattern of preschool children that had certain degree of science. According to the characteristics of the four dietary patterns extracted in this study, children's dietary interventions can be targeted to promote children's physical and mental health.

Systematic construction of undergraduate curriculum for rehabilitation based on WHO rehabilitation competency framework / 中国康复理论与实践

ObjectiveTo systematically develop the courses of rehabilitation based on World Health Organization rehabilitation competency framework (RCF). MethodsThe theories and methods of RCF were used to analyze competency characteristics of rehabilitation workers and educational objectives to construct the curriculum contents in rehabilitation. ResultsThe competency of the rehabilitation workers included practice, professionalism, learning and development, management and leadership, research, values and beliefs in the specific rehabilitation situations. The objectives of rehabilitation medicine education needed to correspond to the competencies of the rehabilitation workers and set up knowledge units that could develop competency in terms of behaviour, activity tasks and proficiency. The curriculum systems of rehabilitation with RCF included the fields of rehabilitation physiotherapy, rehabilitation occupational therapy, hearing and speech rehabilitation, and prosthetic and orthopaedic engineering, etc. ConclusionThe teaching objectives corresponding to the competency characteristics of rehabilitation workers need to be translated into competency-based education. The curriculum contents in rehabilitation needs to be systematically constructed based on RCF from the areas of rehabilitation physiotherapy, rehabilitation occupational therapy, hearing and speech rehabilitation, and prosthetic and orthopaedic engineering.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Buyang Huanwu Decoction Ameliorates Damage of Erectile Tissue and Function Following Bilateral Cavernous Nerve Injury / 中国结合医学杂志

OBJECTIVE@#To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP).@*METHODS@#The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining.@*RESULTS@#The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01).@*CONCLUSIONS@#BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.

Quick guideline for diagnosis and treatment of novel coronavirus Omicron variant infection / 中华临床感染病杂志

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

Changes of uterine morphology and endometrial T2 signal intensity in the fibrotic repair secondary to endometrial injury / 中华妇产科杂志

Objective: To investigate the value of uterine morphological parameters and endometrial T2 signal intensity (T2-SI) in evaluating the degree of the fibrotic repair secondary to endometrial injury. Methods: From Sep. 2018 to Feb. 2023, this study prospectively enrolled 29 patients with fibrotic repair secondary to severe endometrial injury (severe group), 17 patients with fibrotic repair secondary to mild to moderate endometrial injury (mild to moderate group), and 40 healthy women of reproductive age (control group) in Nanjing Drum Tower Hospital. The length of uterine cavity (LUC), length of cervix and isthmus (LCI), width of upper uterine cavity (WUUC) and width of lower uterine cavity (WLUC) were measured using magnetic resonance imaging. T2-SI of endometrium and subcutaneous fat of buttocks were measured, and endometrial normalized T2-SI (nT2-SI; T2-SI of endometrium/T2-SI of subcutaneous fat of buttocks) was calculated. Statistical analyses of data were performed using one-way analysis of variance, Mann-Whitney U test, intraclass correlation coefficient, Spearman rho test, area under the receiver operating characteristic curve (AUC). Results: LUC, WUUC, WLUC and endometrial nT2-SI of severe group [(19.7±3.5) mm, (26.9±6.4) mm, (7.9±1.4) mm, 0.73±0.11, respectively] were significantly lower than those of the control group (all P<0.01), while LCI and WUUC/LUC [(51.3±7.3) mm and 1.38±0.34] were significantly higher than those of the control group (all P<0.001). LUC and WLUC of severe group were significantly lower than those of mild to moderate group [(32.4±5.1) mm and (8.8±1.2) mm; all P<0.05], while LCI and WUUC/LUC were significantly higher than those of mild to moderate group [(41.8±8.6) mm and 0.94±0.16; all P<0.001]. LUC and endometrial nT2-SI of mild to moderate group were significantly lower than those of the control group [ (32.4±5.1) vs (35.3±3.5) mm, 0.68±0.13 vs 0.80±0.12; all P<0.01]. LUC, WUUC, WLUC and endometrial nT2-SI were significantly negatively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho:-0.794, -0.441, -0.471 and -0.316, respectively; all P<0.05), while LCI and WUUC/LUC were significantly positively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho: 0.481 and 0.674, respectively; all P<0.05). LUC and WUUC/LUC showed high value in distinguishing severe group from the control group or mild to moderate group (all AUC>0.9, all P<0.001). Conclusion: As noninvasive and quantitative biomarkers, uterine morphological parameters and endometrial nT2-SI could evaluate the degree of the fibrotic repair secondary to endometrial injury.

Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments / 中国中药杂志

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

Relationship between expression of chemokine receptor 2 and basic fibroblast growth factor in aqueous humor and prognosis of trabeculectomy in patients with acute primary angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the relationship between the levels of chemokine receptor 2(CXCR2)and basic fibroblast growth factor(bFGF)in aqueous humor and the prognosis of trabeculectomy in patients with acute primary angle-closure glaucoma(APACG).METHODS: A total of 80 cases(80 eyes)APACG patients who underwent trabeculectomy in our hospital from June 2020 to January 2022 were collected in the case group. According to the postoperative efficacy, they were grouped into a success group of 60 cases(60 eyes)and a failure group of 20 cases(20 eyes). Another 86 cataract patients(86 eyes)who underwent phacoemulsification with normal intraocular pressure in our hospital during the same period were included in the control group. Enzyme linked immunosorbent assay was applied to detect the levels of CXCR2 and bFGF in aqueous humor. ROC curve was applied to analyze the value of predicting trabeculectomy failure in APACG patients by the levels of CXCR2 and bFGF in aqueous humor. Furthermore, multivariate Logistic regression was applied to analyze the influencing factors of trabeculectomy failure in APACG patients.RESULTS: The levels of CXCR2 and bFGF in the aqueous humor of the case group were significantly higher than those of the control group(P&#x003C;0.05). The levels of CXCR2 and bFGF in the aqueous humor of the failed group and the proportion of patients with postoperative shallow anterior chamber were significantly higher than those of the successful group(P&#x003C;0.05). The AUC for predicting trabeculectomy failure in APACG patients using CXCR2 and bFGF levels alone and in combination was 0.885, 0.883 and 0.953, respectively. CXCR2 and bFGF were independent risk factors for trabeculectomy failure in APACG patients(P&#x003C;0.05).CONCLUSION: The levels of CXCR2 and bFGF in the aqueous humor of APACG patients are obviously elevated, and both are risk factors for trabeculectomy failure.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

The efficacy and safety of epidural morphine/hydromorphone in the treatment of intractable postherpetic neuralgia: A single-center, double-blinded, randomized controlled, prospective, and non-inferiority study.

Objective: Postherpetic neuralgia (PHN) is a clinical puzzle, especially in patients who still suffered from moderate and severe pain after standard treatment. This single-center, double-blinded, randomized controlled, prospective, and non-inferiority study observed the safety and effectiveness of the epidural application of morphine or hydromorphone, trying to provide an alternative method for those patients with refractory PHN. Methods: Eighty PHN patients with a visual analogue scale (VAS) still greater than 50 mm after routine management were randomly divided into two groups according to 1:1, respectively. One group received epidural morphine (EMO group), and the other group received epidural hydromorphone (EHM group). VAS, the number of breakthrough pain, quality of life (QOL), and anxiety/depression assessment (GAD-7 and PHQ-9 scores) were also observed before treatment, at 1, 3, 7, 14, 21, 28, 60, and 90 days after treatment, as well as side effects. Opioid withdrawal symptoms (OWSs) were also measured from 3 to 28 days after treatment. Results: The EHM group was non-inferior to the EMO group in terms of the VAS decrease relative to baseline (VDRB) after 1-week treatment. The VAS of the two groups on all days after treatment was significantly lower than the corresponding baseline findings (p < 0.05). The breakthrough pain (BTP) decreased significantly after treatment and lasted until 14 days after treatment (p < 0.05). There was no significant difference in BTP between the two groups at each time point (p > 0.05). In terms of the QOL, GAD-7, and PHQ-9 outcomes, those were significantly improved after treatment (p < 0.05), and there was no difference between the two groups (p > 0.05). No significant AE difference across the two groups was observed in this study. Few reports of OWS were found in this trial, and there were no significant differences between the two groups (p > 0.05). Conclusion: EHM was non-inferior to EMO in terms of the VDRB after 1-week treatment. For patients with VAS still greater than 50 mm after standard treatment, short-term application of EMO or EHM can ameliorate intractable pain, improve the quality of life, and have no obvious side effects. Short-term epidural opioid application will not lead to the appearance of OWS.

Role of the Guanidinium Groups in Ligand-Receptor Binding of Arginine-Containing Short Peptides to the Slow Sodium Channel: Quantitative Approach to Drug Design of Peptide Analgesics.

Several arginine-containing short peptides have been shown by the patch-clamp method to effectively modulate the NaV1.8 channel activation gating system, which makes them promising candidates for the role of a novel analgesic medicinal substance. As demonstrated by the organotypic tissue culture method, all active and inactive peptides studied do not trigger the downstream signaling cascades controlling neurite outgrowth and should not be expected to evoke adverse side effects on the tissue level upon their medicinal administration. The conformational analysis of Ac-RAR-NH2, Ac-RER-NH2, Ac-RAAR-NH2, Ac-REAR-NH2, Ac-RERR-NH2, Ac-REAAR-NH2, Ac-PRERRA-NH2, and Ac-PRARRA-NH2 has made it possible to find the structural parameter, the value of which is correlated with the target physiological effect of arginine-containing short peptides. The distances between the positively charged guanidinium groups of the arginine side chains involved in intermolecular ligand-receptor ion-ion bonds between the attacking peptide molecules and the NaV1.8 channel molecule should fall within a certain range, the lower threshold of which is estimated to be around 9 Å. The distance values have been calculated to be below 9 Å in the inactive peptide molecules, except for Ac-RER-NH2, and in the range of 9-12 Å in the active peptide molecules.

Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome / 中华临床感染病杂志

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

Assessment of effects of intra-abdominal pressure monitoring on evaluating early enteral nutrition in patients with acute pancreatitis / 中华危重病急救医学

Objective:To explore the role of intra-abdominal pressure (IAP) monitoring in evaluating the efficacy of early enteral nutrition (EN) in patients with acute pancreatitis (AP).Methods:The clinical data were collected from the AP patients in department of criticle care medicine of Baoshan Branch of Huashan Hospital Affiliated to Fudan University from July 2020 to June 2021. The patients were divided into three groups according to their treatments: no gastrointestinal decompression with fasting group, gastrointestinal decompression with fasting group, gastrointestinal decompression with indwelling jejunal tube within 24 hours group. The data of white blood cell (WBC), procalcitonin (PCT), serum amylase (AMY) and IAP were analyzed before and after treatment, the initiation time oral feeding were also analyzed.Results:The decrease of WBC, PCT, AMY, and IAP in gastrointestinal decompression with indwelling jejunal tube within 24 hours group were significantly greater than those in the other groups [WBC (×10 9/L): -1.72±0.74 vs. -0.68±0.36, -1.23±86.97; PCT (μg/L): -3.14±5.19 vs. 0.06±0.48, -1.57±0.78; AMY (U): -148.43±75.89 vs. -74.85±78.84, -93.78±1.17; IAP (cmH 2O, 1 cmH 2O≈0.098 kPa): -4.82±1.66 vs. 0.36±1.32, -3.22±4.36, all P < 0.05]. There were no correlation between the changes of IAP and the changes of WBC, PCT or AMY in the non-gastrointestinal decompression with fasting group and the gastrointestinal decompression with indwelling jejunal tube within 24 hours group (all P > 0.05). The decreasing trend of IAP in patients with gastrointestinal decompression with fasting group was positively correlated with the change of AMY ( r = 0.65, P < 0.001). The initiation time of oral feeding in gastrointestinal decompression with indwelling jejunal tube within 24 hours group was significantly shorter than that in the other groups (hours: 89.538 vs. 111.273, 109.714), the difference was statistically significant ( P < 0.05). Conclusions:IAP monitoring, as an emergency means of monitoring the efficacy of early EN in AP patients, has the advantages of simplicity, efficiency and rationality, which has a more objective basis than the previous empirical treatment and open oral feeding.

Expert statement on the construction criteria of critical care department in municipal and district designated hospitals under the pandemic prevention and control / 中华危重病急救医学

The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.

Analysis of factors affecting the burden of caregivers of elderly patients with chronic diseases / 预防医学

Objective@#To investigate the burden of caregivers of elderly patients with chronic diseases and its influencing factors, so as to provide the evidence for reducing the burden of caregivers.@* Methods@#The caregivers of patients with chronic diseases at ages of 65 years and older were selected using convenience sampling method from Jinqiu Hospital during 2020 and 2021. The burden of caregivers was estimated using Chinese version of Caregiver Burden Scale (CBI), the basic information of patients and caregivers was collected, and the influencing factors of caregivers' burden were identified using multivariable linear regression analysis.@*Results@#Totally 276 questionnaires were distributed, and 261 were valid, with an effective rate of 94.57%. There were 48 men (18.39%) and 213 women (81.16%), 166 (63.60%) subjects aged 45 to 59 years and 354 (82.38%) subjects participating in training on COVID-19 prevention. The mean score of caregivers' burden was 26.27±14.93, and the mean scores of social burden and emotional burden were 11.08±5.23 and 7.81±6.24, respectively. The patients with chronic diseases included 183 men (70.11%), had a mean age of (89.97±8.26) years, had a mean score of activities of daily living of 20.00 (interquartile range, 50.00) and had a mean geriatric syndrome number of 4.10±1.57. Multivariable linear regression analysis identified caregivers' participating in training on COVID-19 prevention (β'=0.175), patients' activities of daily living (β'=-0.144), patients' geriatric syndrome number (β'=0.138) and patients' age (β'=0.162) as factors affecting the burden of caregivers.@*Conclusions@#The social and mental burden of the caregivers of elderly patients with chronic diseases is heavy, and patients' activities of daily living, number of geriatric syndromes and age, as well as caregivers' training on COVID-19 prevention may be associated.

Gadoxetate-Enhanced MRI as a Diagnostic Tool in the Management of Hepatocellular Carcinoma:Report from a 2020 Asia-Pacific Multidisciplinary Expert Meeting

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.