A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of Qingjie Huagong decoction （QJHGD） on a mouse model of severe acute pancreatitis （SAP） and the mechanism of action of QJHGD against inflammatory response. MethodsA total of 36 male C57BL/6J mice were randomly divided into blank group， model group， Western medicine group （ulinastatin）， and low-， middle-， and high-dose QJHGD groups， with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling， the mice in the low-， middle-， and high-dose groups were given QJHGD （1， 2， and 4 g/kg， respectively） by gavage， and those in the Western medicine group were given intraperitoneal injection of ulinastatin （5×104 U/kg）， for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas； ELISA was used to measure the levels of α-amylase， lipase， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α） in mice； RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 （NLRP3）， Toll-like receptor 4 （TLR4）， and nuclear factor-kappa B （NF-κB） in pancreatic tissue； immunohistochemistry was used to measure the positive expression rates of NLRP3， TLR4， and NF-κB in pancreatic tissue； Western blot was used to measure the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group， the model group had diffuse destruction of pancreatic tissue structure， focal dilatation of pancreatic lobular septum， pancreatic acinar atrophy， and massive inflammatory cell infiltration， as well as significant increases in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. Compared with the model group， the low-， middle-， and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue， ordered arrangement of pancreatic acinar cells， a small amount of inflammatory cell infiltration， and hemorrhagic foci of pancreatic lobules， as well as significant reductions in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. ConclusionQJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins， reducing the release of inflammatory mediators， and preventing the enhancement of inflammatory cascade response.

Impaired cholesterol metabolism affecting subventricular zone neurogenesis in ob/ob mice / 解剖学报

Objective To investigate the effect of cholesterol on the proliferation and differentiation of neural stem cells (NSCs) in ob/ob obese mice, and to explore the possible mechanism of central nervous systym dysfunction caused by obesity. Methods Selected 64-month-old ob/ob and wild type (WT) mice, and cell proliferation antigen (Ki67) and doublecortin (DCX) immunofluorescenct staining were used to detect ob/ob mice lateral ventricle subventricular zone (SVZ) neurogenesis level. Cultured SVZ NSCs isolated from 184-month-old ob/ob and WT mice, and BrdU incorporation experiment and β-III-tubulin (Tuj1) immunofluorescent staining were employed to detect the self-renewal and differentiation ability of NSCs. Matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI- MS)was used to detect the lipid distribution in 4-month-old ob/ob and WT mice brain tissues, and measure the changes of cholesterol(ST) content and the expression genes related to cholesterol synthesis. Cultured 15 WT postnatal day 0(P0) mouse SVZ NSCs in vitro and electrotransfected with the small interfering RNA(siRNA) sequence of cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (Hmgcr) verified the knockdown efficiency, to detecte the effect of Hmgcr gene knockdown on NSCs by BrdU incorporation experiment and Tuj1 immunofluorescent staining. Results Compared with the WT mice, the number of Ki67

Inhibition of MAPK pathway-induced apoptosis in renal cancer cells by ethanol extraction of Dysosma versipellis / 中国药理学通报

Aim To explore the effects of ethanol extraction of Dysosma versipellis on the proliferation and apoptosis of renal clear cell carcinoma OS-RC-2 cells and the underlying mechanism. Methods After treated with Dysosma versipellis, the proliferation of OS-RC-2 cells was detected by the CCK-8 assay and clone formation assay. The migration rate of cells was detected by thewound healing assay and Transwell assay. The level of ROS was detected by the reactive oxygen detection kit. The common targets between Dysosma versipellis and ROS were obtained by the network pharmacology. The above common targets were analyzed by KEGG. The apoptosis rate and cell cycle were detected by the flow cytometry, and the key proteins of MAPK signaling pathway and the levels of apoptosis related proteins were measured by Western blot. Results The results showed that Dysosma versipellis significantly inhibited the cell viability and migration ability of 0S-RC-2 cells, and up-regulated the level of ROS. Network pharmacology analysis showed a total of 165 common targets between Dysosma versipellis and ROS. KEGG analysis of the common targets revealed that there were significant changes in the MAPK signaling pathway. The results of Western blot showed that after treated with Dysosma versipellis, the protein level of JNK and the ratio of p-ERK/ERK were down-regulated. Besides, the protein level of caspase-9 and Bcl-2 declined, while the levels of cleaved caspase-9 and Bax were promoted. The flow cytometry results showed that Dysosma versipellis could significantly promote the apoptosis rate,down-regulate the cells in Gl-phase,while up-regulate the cells in G2/M-phase. The results of the rescue experiment showed that co-administration of NAC and Dysosma versipellis could significantly reverse the cell viability and apoptosis rate, the level of apop-totic related proteins, as well as the protein levels of MAPK pathway,when compared to treated with Dysosma versipellis alone in OS-RC-2. Conclusion In summary, Dysosma versipellis may inhibit the MAPK signaling pathway via the changes in ROS,further promoting apoptosis rate and decline cell proliferation in OS-RC-2 cell line.

Bioinformatics analysis of sterol O⁃acyltransferase 1 gene related to hepatocellular carcinoma / 中国生物制品学杂志

@#Abstract：Objective To predict the structure and function of sterol O⁃acyltransferase 1（SOAT1）related to hepatocellular carcinoma（HCC）by using bioinformatics tools，in order to understand its mechanism as the marker and therapeutic target of S⁃Ⅲ subtype. Methods The structure，function and protein interaction of SOAT1 were predicted and analyzed by using databases or softwares such as NCBI，STRING，Protscale，SignalP，TMHMM，PSORT，SOPMA，SWISS ⁃ MODEL， NetNGlyc，NetOGlyc，Netphos and ProtParam. Results The protein encoded by SOAT1 was a hydrophobic protein with good stability，which was a nonclassical pathway protein with 8 transmembrane regions，mainly distributed among the cell membrane. SOAT1 was expressed in many tissues，while most of them in the adrenal gland，which showed multiple phosphorylation sites and was mainly involved in the synthesis and catabolism of cholesterol. Conclusion Bioinformatics analysis of structure and function of SOAT1 showed that SOAT1 lipid synthesis and catabolism pathways played an important role，and lipid expression was closely related to the development of cancer，indicating that the treatment of HCC may be achieved by regulating the expression of SOAT1 gene.

Applicability comparison between Chinese dry eye questionnaire and ocular surface disease index questionnaire among college students / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the applicability of Chinese dry eye questionnaire in college students using the ocular surface disease index(OSDI)questionnaire as a reference.METHODS: Cross-sectional study. A total of 711 college students from Nanyang Medical College were enrolled in the study and assessed for dry eye condition using OSDI questionnaire and Chinese dry eye questionnaire. The response rate of each question in the two questionnaires was counted. Cronbach α was calculated to evaluate the internal consistency of both questionnaires. Correlation between the total scores of the two questionnaires was analyzed to evaluate the criterion validity. Based on OSDI scores, the discriminant validity of Chinese dry eye questionnaire was evaluated; receiver operating characteristic(ROC)curves was plotted for Chinese dry eye questionnaire scores, area under the ROC curve(AUC)was calculated, and diagnostic thresholds and corresponding sensitivity and specificity were also analyzed.RESULT: The response rates of the 12 questions on the OSDI questionnaire were 33.2%-100.0%, while it was 100.0% for each question on the Chinese dry eye questionnaire. The Cronbach α values of OSDI questionnaire and Chinese dry eye questionnaire were 0.905 and 0.789, respectively. The Chinese dry eye questionnaire score was positively correlated with the OSDI score(rs=0.712, P&#x003C;0.001). According to OSDI questionnaire scores, dry eye severity was divided into normal group, mild dry eye group, moderate dry eye group and severe dry eye group. The scores of Chinese dry eye questionnaire in these groups were 4.00(2.00, 6.00), 9.00(7.00, 11.00), 12.00(9.00, 14.00)and 16.00(13.50, 22.00), respectively, which increased with the severity of dry eye, and the overall difference was statistically significant(P&#x003C;0.001), as well as pairwise comparison between groups(P&#x003C;0.05). The AUCs of Chinese dry eye questionnaire in distinguishing normal population from dry eye population, mild dry eye from moderate dry eye, moderate dry eye from severe dry eye were 0.862, 0.661 and 0.769, respectively, and the diagnostic thresholds were 6.5, 11.5 and 14.5, respectively.CONCLUSION:Chinese dry eye questionnaire has an equivalent reliability, validity, discriminant ability and better response rate for dry eye screening and epidemiological survey among college students in China compared with OSDI questionnaire.

Value of normalized apparent diffusion coefficient in predicting HER2 expression in bladder cancer / 现代泌尿外科杂志

【Objective】 To predict the expression of human epidermal growth factor receptor 2 (HER2) in urothelial bladder carcinoma based on normalized apparent diffusion coefficient (ADC). 【Methods】 The preoperative pelvic 3.0T magnetic resonance imaging (MRI) images of 127 patients with urothelial bladder carcinoma were retrospectively studied, the ADC was measured, and the HER2 expression in postoperative tissue specimens was determined with immunohistochemistry (IHC). The differences in normalized ADC were analyzed among different HER2 expressions and among different expression divisions. Correlation between normalized ADC and HER2 expression was analyzed. The optimal diagnostic threshold for distinguishing different expression divisions were determined with receiver operating characteristic (ROC) curve. 【Results】 Normalized ADC was negatively correlated with HER2 expression (tau-b=-0.180, P=0.008). Normalized ADC of HER2 overexpression group (IHC 2+, 3+) was lower than that of HER2 negative group (IHC 0, 1+) (P=0.081). Normalized ADC of HER2 expression group (IHC 1+, 2+, 3+) was significantly lower than that of HER2 zero-expression group (IHC 0) (P=0.020). Normalized ADC of HER2 strong positive group (IHC 3+) was significantly lower than that of HER2 non-strong positive group (IHC 0, 1+, 2+) (P=0.024). The optimal diagnostic threshold of HER2 strong positive group was 0.849; the sensitivity, specificity and accuracy were 0.621, 0.909 and 0.765, respectively. The optimal diagnostic threshold of HER2 overexpression group was 0.909; the sensitivity, specificity and accuracy were 0.547, 0.667 and 0.607, respectively. 【Conclusion】 Normalized ADC is negatively correlated with HER2 expression. ADC may be a potential marker for predicting HER2 expression.

Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Return to sports WeChat applet for evaluating the rehabilitation effects after anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To clarify the intervention guidance of return to sports WeChat applet and evaluate the rehabilitation effectiveness after anterior cruciate ligament (ACL) reconstruction.@*METHODS@#Between September 2020 and September 2022, 80 patients who met the selection criteria and underwent ACL anatomical single bundle reconstruction were selected as the research objects. According to the double-blind random method, they were divided into the applet group and the regular group, with 40 cases in each group. Patients in the applet group were rehabilitated under the guidance of the return to sports WeChat applet, and the patients were asked to perform the test once a month after operation, including patients' subjective scores [Tegner score, knee injury and osteoarthritis outcome score (KOOS), International Knee Documentation Committee (IKDC) score, American Hospital for Special Surgery (HSS) score], psychological assessment [ACL recovery sports injury scale (ACL-RSI) score], jumping test, balance test, bending angle test. Patients in the regular group were followed up by doctors and nurses regularly by telephone every month. All the patients were reexamined at 3, 6, 9, and 12 months after operation, and the range of motion of the knee joint with 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, and internal and external displacement) recorded by Opti_Knee three-dimensional knee joint motion measurement gait analysis system was observed. The anterior tibial translation difference (ATTD) was measured by Ligs knee measuring instrument when a forward thrust of 120 N was applied to the posterior part of the proximal tibia. Tegner score, IKDC score, KOOS score (including KOOS-Pain score, KOOS-Symptoms score, KOOS-Activities of daily living score, KOOS-Sport score, and KOOS-Quality of life score), HSS score, ACL-RSI score, jumping ability, balance ability, patients' satisfaction with the rehabilitation process, and ACL healing grading according to ACL continuity and signal intensity shown by MRI.@*RESULTS@#There were significant differences in various indicators between different time points after operation in the two groups ( P<0.05). At 3 months after operation, except that the ACL-RSI score of the applet group was significantly higher than that of the regular group ( P<0.05), there was no significant difference in the other indicators between the two groups ( P>0.05). At 6 months after operation, the ACL-RSI score, IKDC score, Tegner score, KOOS scores of different items, HSS score, balance and jumping ability of the applet group were significantly higher than those of the regular group ( P<0.05), and there was no significant difference in the other indicators between the two groups ( P>0.05). At 9 months after operation, there was no significant difference in all indicators between the two groups ( P>0.05). At 12 months after operation, 27 cases (67.5%) in the applet group and 21 cases (52.5%) in the regular group returned to sport, with a significant difference of the return to sports incidence between the two groups [ RR(95% CI)=1.50 (1.00, 2.25), P=0.049]. In the applet group, 27 cases were very satisfied with the rehabilitation process, 10 cases were satisfied, 2 cases were basically satisfied, and 1 case was not satisfied, while 19, 13, 5, and 3 cases in the regular group, respectively. The satisfaction degree of the applet group was significantly better than that of the regular group ( P=0.049). MRI examination of the two groups showed that the ACL was continuous without secondary rupture or necrosis. The ACL healing grade of the applet group was 31 cases of grade 1 and 9 cases of grade 2, and that of the regular group was 28 cases of grade 1 and 12 cases of grade 2, there was no significant difference in ACL healing grade between the two groups ( P=0.449).@*CONCLUSION@#The application of return to sports WeChat applet in the rehabilitation of patients after ACL reconstruction can significantly reduce the fear of return to sports and improve the rate of return to sports. The return to sports WeChat applet is convenient to operate, with high utilization rate and high patient compliance, which significantly improves the satisfaction.

Research on genetic model of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of genetic factors on the pathogenesis of keratoconus and its genetic model.METHODS: Genetic epidemiological methods were used to investigate the prevalence of keratoconus in 280 first-degree relatives of 100 patients with keratoconus who attended Henan Eye Hospital between July 2020 and April 2023. The heritability was estimated by Falconer regression method. The general genetic model was calculated using Penrose method, and the genetic model was confirmed by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory.RESULTS: The results showed that there were 16(5.714%)first-degree relatives of keratoconus probands suffering from keratoconus, and the heritability of keratoconus was(86.100±7.400)%. The S/q score calculated by the Penrose method was 35.348, which was near to 1/(q)1/2, suggesting that the genetic model of keratoconus might be polygenic inheritance. The expected prevalence in first-degree relatives of keratoconus patients by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory were 5.900%, 7.714% and 5.700%, respectively, which showed no significant differences from the actual prevalence(5.714%), suggesting that keratoconus was a polygenetic disease.CONCLUSION:Genetic factors might play an important role in the pathogenesis of keratoconus, and keratoconus is a polygenetic disease.

A case of delayed peripheral neuropathy caused by diquat poisoning / 中华劳动卫生职业病杂志

Diquat is a kind of conductive contact-killing herbicides. The damage of central nervous system is relatively common, but the peripheral neuropathy caused by diquat has not been reported yet. In September 2021, we treated a patient with diquat poisoning. During the hospitalization, the patient was diagnosed with peripheral neuropathy. Therapy for peripheral nerve injury was given on the basis of conventional treatment of poisoning. The patient was discharged after his condition was stable. The follow-up showed that the peripheral neuropathy of patient was better than before. According to the condition of this patient, it is suggested that we should not only protect the function of gastrointestinal tract, liver, kidney, and central nervous system early, but should also pay attention to the damage of peripheral nervous system in clinical work. We should intervene earlier to improve the prognosis of patients.

Study on the mechanism of Yiyi Fuzi powder in the treatment of rheumatoid arthritis based on metabolomics and network pharmacology / 药学学报

In this study, a combination of metabolomics and network pharmacology was used to study the pharmacodynamic substances and mechanism of action of Yiyi Fuzi powder (YYFZ) on rheumatoid arthritis (RA) rats. The animal experiments were conducted in accordance with the requirements of the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (approval number: TCM-LAEC2021241). The metabolomic analysis using UPLC-Q-TOF/MS technique identified 22 metabolites, including arachidonic acid, tryptophan, linoleic acid, phenylalanine, as significant biomarkers for the treatment of RA with YYFZ, and they were significantly regressed after YYFZ treatment. The analysis of YYFZ blood components also revealed that 11 blood components, including hypaconitine, benzoylhypaconitine, and deoxyaconitine, may be the components that exert direct pharmacological effects in YYFZ in vivo, and further network pharmacological analysis of blood components obtained that YYFZ may exhibit anti-inflammatory effects through acting on PI3K/Akt signaling pathway, estrogen signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway. The results of this study provide implications for the clinical application of YYFZ.

Application value of new assistive technology in keratopathy-associated cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

Keratopathy-associated cataract, that is, on the basis of corneal disease, and later the development of lens opacity, seriously damage visual quality. In order to avoid corneal transplantation for some patients, partial visual quality can be restored. A comprehensive and accurate evaluation of the effect of corneal opacity on visual function is of great improtance for determining cataract surgery alone. Due to the opacity of the cornea, the operation is very difficult and challenging. Therefore, it is of clinical value to develop and use new assistive technologies, including capsule staining, endoillumination, pupil dialation technology, femtosecond laser assisted technology, etc., avoiding problems such as limited visibility and decreased light flow caused by corneal opacity and facilitating cataract surgery. This article reviews progress of assistive technologies for keratopathy-associated cataract, hoping to guide clinical application.

Construction of cough reflex intensity score for critically ill patients based on the Delphi method / 世界急诊医学杂志（英文）

@#Airway management is important for critically ill patients. Improper airway management can directly threaten the life of patients.[1] Early correct airway assessment and effective airway management can improve patient prognosis.[2] Coughing ability plays an important role in the decision-making process of airway management. Patients with impaired coughing ability have a higher risk of tracheal intubation during treatment. The concept of cough strength was first proposed by Khamiees in 2001,[3] but the evaluation criteria did not include coughing ability. The purpose of this study was to assess patients’ coughing ability through the Delphi method and expert consultation, to provide data support for establishing a cough reflex intensity score and to construct an advanced airway management model for quick and effective evaluation.[4,5]

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

Overview of systematic reviews of Chinese herbal injections for sepsis / 中国中药杂志

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

Application of four intraocular lens calculation formulas in patients with super-high myopia complicated with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the accuracy of SRK/T, Haigis, Barrett Universal II and Wang-Koch modified SRK/T formula in the operation of cataract complicated by super-high myopia.METHODS: A total of 44 cases(52 eyes)with super-high myopia complicated with cataract who underwent phacoemulsification with tension ring implantation combined with intraocular lens implantation in our hospital from January 2020 to June 2021 were collected. SRK/T, Haigis, Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula were used to calculate the postoperative reserved diopter before surgery, and the actual diopter was measured by comprehensive optometry at 3mo after surgery. The mean absolute refractive error(MAE)of four formulas was obtained to evaluate the accuracy of the calculation formula.RESULTS: The MAE of SRK/T formula, Haigis formula, Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula were 0.86(0.56, 1.20), 0.79(0.56, 1.16), 0.68(0.30, 0.87), 0.65(0.43, 0.75)D, respectively, and MAE of SRK/T formula and Haigis formula were significantly higher than those of Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula(P<0.01). According to preoperative corneal curvature(K), enrolled patients were divided into K >46D group(12 eyes), 44D< K ≤46D group(24 eyes), and K ≤44D group(16 eyes). The MAE of SRK/T formula and Haigis formula were significantly higher than those of Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula in the three groups(P<0.01). According to preoperative axial length(AL), patients were divided into AL ≤30 mm group(24 eyes)and AL >30mm group(28 eyes). The MAE of SRK/T formula and Haigis formula in two groups were significantly higher than those of Barrett Universal Ⅱ formula and Wang-Koch modified SRK/T formula(P<0.05).CONCLUSIONS: Wang-Koch modified SRK/T formula and Barrett Universal Ⅱ formula are more accurate in predicting the degree of intraocular lens in patients with super-high myopia complicated with cataract.

Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells / 中国中药杂志

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Report on Cardiac Gross Pathologic Measurements of Sudden Cardiac Death in Adults / 法医学杂志

OBJECTIVES@#To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes.@*METHODS@#A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed.@*RESULTS@#The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05).@*CONCLUSIONS@#Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.

Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry / 대한뇌졸중학회지

Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.