Application of magnetic resonance imaging-proton density fat fraction in liver fat quantification / 临床肝胆病杂志

Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis， cholestatic liver disease， alcoholic liver disease， and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis， followed by steatohepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. With the development of medical imaging technology， magnetic resonance imaging-proton density fat fraction （MRI-PDFF） has been widely used in the diagnosis of fatty liver disease （FLD） in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.

Relationship between cerebrovascular reserve capacity and white matter lesions in the elderly based on magnetic resonance imaging / 中国辐射卫生

Objective To investigate the relationship between cerebrovascular reserve (CVR) capacity and white matter lesions in elderly people. Methods We included 315 participants aged ≥ 60 years in Jinan area of Shandong Province from May 2018 to July 2019. They underwent transcranial Doppler ultrasonography for assessing CVR, breath holding index (BHI), and arterial pulsatility index (PI). According to CVR capacity, they were divided into normal CVR group (CVR ≥ 20%, n = 206) and impaired CVR group (CVR < 20%, n = 109). Magnetic resonance imaging was performed to evaluate periventricular, subcortical, and total white matter hyperintensity (WMH) volumes and Fazekas scores. Results Compared with the normal CVR group, the impaired CVR group showed significantly higher volumes of periventricular, subcortical, and total WMHs and significantly higher proportions of Fazekas scores ≥ 2 (P < 0.01). Periventricular, subcortical, and total WMH volumes were negatively correlated with CVR (r = −0.70, −0.66, −0.73, P < 0.01) and BHI (r = −0.64, −0.65, −0.68, P < 0.01) and positively correlated with PI (r = 0.60, 0.65, 0.65, P < 0.01). After adjusting for confounding factors, periventricular, subcortical, and total WMH volumes were still negatively correlated with CVR and BHI (P < 0.01) and positively correlated with PI (P < 0.01). The logistic regression analysis showed that the risks of periventricular, subcortical, and total Fazekas score ≥ 2 in the impaired CVR group were 1.96 times (95% confidence interval [CI]: 1.17−3.27, P < 0.01), 1.84 times (95% CI: 1.11−3.05, P < 0.05), and 2.33 times (95% CI: 1.30−4.18, P < 0.01) that of the normal CVR group, respectively. Conclusion Impaired CVR is an independent risk factor for white matter lesions in the elderly.

Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children / 中国当代儿科杂志

OBJECTIVES@#To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children.@*METHODS@#A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed.@*RESULTS@#The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05).@*CONCLUSIONS@#Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Male reproductive system and simulated high-altitude environment: preliminary results in rats / 亚洲男科学杂志(英文版)

This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.

Relationship of Microvascular Obstruction with Global and Regional Myocardial Function Determined by Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction / 中国医学科学杂志(英文版)

Objective To investigate the impact of microvascular obstruction (MVO) on the global and regional myocardial function by cardiac magnetic resonance feature-tracking (CMR-FT) in ST-segment-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1 - 7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study. Based on the presence or absence of MVO on late gadolinium enhancement images, patients were divided into groups with MVO and without MVO. The infarct zone, adjacent zone, and remote zone were determined based on a myocardial 16-segment model. The radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle (LV) and the infarct, adjacent, and remote zones were measured by CMR-FT from cine images and compared between patients with and without MVO using independent-samples t-test. Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients (mean age 56.66 ± 11.38 years) were enrolled. MVO was detected in 37.58% (59/157) of STEMI patients, and the mean size of MVO was 3.00 ±3.76 mL. Compared with patients without MVO (n =98 ), the MVO group had significantly reduced LV global RS (t= -4.30, P < 0.001), global CS (t= 4.99, P < 0.001), and global LS ( t= 3.51, P = 0.001). The RS and CS of the infarct zone in patients with MVO were significantly reduced (t= -3.38, P = 0.001; t= 2.64, P = 0.01; respectively) and the infarct size was significantly larger (t= 8.37, P < 0.001) than that of patients without MVO. The presence of LV MVO [OR= 4.10, 95%CI: 2.05 - 8.19, P<0.001) and its size [OR=1.38, 95%CI: 1.10-1.72, P=0.01], along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis, while only heart rate (OR=1.08, 95%CI: 1.03 - 1.13, P=0.001) and LV infarct size (OR=1.10, 95%CI: 1.03 - 1.16, P=0.003) were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO, and MVO deteriorates the global and regional LV myocardial function.

Shaofu Zhuyu Decoction attenuates fibrosis in endometriosis through regulating PTEN/Akt/mTOR signaling pathway / 中国中药杂志

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.

DUS testing guidelines for new varieties of Chinese medicinal plants / 中国中药杂志

A rich diversity of wild medicinal plant resources is distributed in China, but the breeding of new plant varieties of Chinese medicinal plants started late and the breeding level is relatively weak. Chinese medicinal plant resources are the foundation for new varieties breeding, and the plant variety rights(PVP) are of great significance for the protection and development of germplasm resources. However, most Chinese medicinal plants do not have a distinctness, uniformity, and stability(DUS) testing guideline. The Ministry of Agriculture and Rural Affairs has put 191 plant species(genera) on protection lists, of which only 30 are medicinal species(genera). At the same time, only 29 of 293 species(genera) plants in the Protection List of New Plant Varieties of the People's Republic of China(Forest and Grass) belong to Chinese medicinal plants. The number of PVP applications and authorization of Chinese medicinal plants is rare, and the composition of variety is unreasonable. Up to now, 29 species(genera) of DUS test guidelines for Chinese medicinal plants have been developed. Some basic problems in the breeding of new varieties of Chinese medicinal plants have appeared, such as the small number of new varieties and insufficient utilization of Chinese medicinal plant resources. This paper reviewed the current situation of breeding of new varieties of Chinese medicinal plants and the research progress of DUS test guidelines in China and discussed the application of biotechnology in the field of Chinese medicinal plant breeding and the existing problems in DUS testing. This paper guides the further application of DUS to protect and utilize the germplasm resources of Chinese medicinal plants.

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.

Exercise regulates bone metabolism via microRNAs / 生理学报

It has been well documented that exercise can improve bone metabolism, promote bone growth and development, and alleviate bone loss. MicroRNAs (miRNAs) are widely involved in the proliferation and differentiation of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts and other bone tissue cells, and regulation of balance between bone formation and bone resorption by targeting osteogenic factors or bone resorption factors. Thus miRNAs play an important role in the regulation of bone metabolism. Recently, regulation of miRNAs are shown to be one of the ways by which exercise or mechanical stress promotes the positive balance of bone metabolism. Exercise induces changes of miRNAs expression in bone tissue and regulates the expression of related osteogenic factors or bone resorption factors, to further strengthen the osteogenic effect of exercise. This review summarizes relevant studies on the mechanism whereby exercise regulates bone metabolism via miRNAs, providing a theoretical basis for osteoporosis prevention and treatment with exercise.

Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists / 中华医学杂志(英文版)

BACKGROUND@#Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.@*METHODS@#Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.@*RESULTS@#A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%).@*CONCLUSION@#The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.@*METHODS@#This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables.@*RESULTS@#As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups.@*CONCLUSION@#The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR 1900023646.

ZHANG Wei-hua's clinical experience of Zhenjing Anshen method in treatment of insomnia / 中国针灸

The paper summarizes professor ZHANG Wei-hua's clinical experience in treatment of insomnia with Zhenjing Anshen (calming-down the spirit) method. It is believed that insomnia results from the unstable spirit in pathogenesis of TCM. The basic therapeutic principle is regulating the spirit, in which, stabilizing the primary spirit and tranquilizing the heart spirit are emphasized. Main acupoints are Baihui (GV 20), Sishencong (EX-HN 1) and Yintang (GV 24+) to stabilize the primary spirit, located on the head; and Shenmen (HT 7) located on the wrist to calm-down the heart spirit, as well as Sanyinjiao (SP 6) and Yongquan (KI 1) in the lower extremities to benefit yin and balance yang, and then to house the spirit eventually. The needles are inserted in different depths and to various directions. The external application of herbal plaster is combined at Yongquan (KI 1) and the supplementary acupoints are selected in terms of syndrome differentiation. This therapy is simple in acupoint selection and very effective in treatment of insomnia.

Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation.@*METHODS@#Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups.@*RESULTS@#Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05).@*CONCLUSION@#The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.

Anti-liver Cancer Mechanisms of Biejiajian Wan and Clinical Research： A Review / 中国实验方剂学杂志

Biejiajian Wan， a classical formula for liver diseases， originated from Synopsis of the Golden Chamber. It has been applied in clinical settings for more than 2 000 years. According to modern pharmacological studies， it has anti-tumor， anti-fibrosis， and immunity-enhancing effects and thus is widely used for the treatment of liver fibrosis， hepatitis， liver injury， and other diseases. In recent years， accumulating evidence has proven the efficacy of this formula in the treatment of malignant tumors， especially liver cancer. This paper summarizes relevant papers in the last 20 years and summed up the anti-liver cancer mechanisms of Biejiajian Wan as regulating biological behaviors of liver cancer cells， anti-precancerosis， inhibiting tumor angiogenesis， modulating signaling pathways， suppressing activity of relevant enzymes， and regulating immunity. Moreover， this prescription can inhibit the proliferation， invasion， and metastasis of liver cancer cells， promote apoptosis of cells， suppress tumor angiogenesis， and boost immunity. In addition， it regulates Wnt/β-catenin， interleukin-6/signal transducer and activator of transcription 3 （IL-6/STAT3）， NOD-like receptor protein 3 （NLRP3）， Janus kinase-signal transducers and activators of transcription （JAK-STAT）， Delta-like ligand 4-Notch （DLL4-Notch）， nuclear factor-κB （NF-κB）， Rho-associated kinase （Rho/ROCK）， transforming growth factor-β/Smad （TGF-β/Smad）， phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3β （PI3K/Akt/GSK-3β）， and other signaling pathways. Thus， Biejiajian Wan is confirmed to have anti-liver cancer effect based on the molecular mechanisms. According to the summary of Biejiajian Wan in anti-liver cancer treatment， Biejiajian Wan alone or in combination with other drugs can significantly alleviate the symptoms， reduce adverse reactions， prolong the survival time with definite efficacy. Thus， it is safe with no adverse reactions in long-term use， which should be further promoted in clinical application. This paper analyzed Biejiajian Wan in the treatment of liver cancer based on the molecular mechanisms and clinical studies， summarized the limitations in current research， and put forward suggestions， which can lay a basis for the future in-depth research on and clinical application of Biejiajian Wan and development of anti-tumor drugs.

Role of intrahepatic microenvironment induced-autophagy in nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is a series of abnormal liver lesions mainly characterized by excessive lipid deposition in hepatocytes, and it is also the most common chronic liver disease worldwide. Autophagy is a basic cellular process in which cells degrade their own components and participate in the maintenance of organ function and body homeostasis, and it is closely associated with the progression of NAFLD. High fat, hypoxia, and stress in human body may cause abnormal changes in extracellular microenvironment in the liver, and such abnormal microenvironment may promote the development and progression of NAFLD by inducing liver cell autophagy. This article reviews the role and mechanism of autophagy of liver cells such as hepatocytes, Kupffer cells, and hepatic stellate cells in the progression of NAFLD based on various microenvironment characteristics in the liver.

Postoperative corneal topography generation based on attention mechanism and Pix2Pix network / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the use of attention mechanism and Pix2Pix generative adversarial network to predict the postoperative corneal topography of age-related cataract patients undergone femtosecond laser arcuate keratotomy.METHODS:In this retrospective case series study, the 210 preoperative and postoperative corneal topographies from 87 age-related cataract patients(105 eyes)undergoing femtosecond laser arcuate keratotomy at Shanxi Eye Hospital between March 2018 and March 2020 were selected and divided into a training set(180)and a test set(30)for model training and testing. The peak signal-to-noise ratio(PSNR), structural similarity(SSIM)and Alpins astigmatism vector analysis were used to compare the accuracy of postoperative corneal topography prediction under different attention mechanisms.RESULTS:The model based on attention mechanism and Pix2Pix network can predict postoperative corneal topography, among which the model based on Self-Attention mechanism has the best prediction effect, with PSNR and SSIM reaching 16.048 and 0.7661, respectively. There were no statistically significant differences in the difference vector, difference vector axis position, surgically induced astigmatism, and correction index between real and generated corneal topography on the 3mm and 5mm rings(all P&#x003E;0.05).CONCLUSION:Based on the Self-Attention mechanism and Pix2Pix network, the postoperative corneal topography can be well predicted, which can provide reference for the surgical planning and postoperative effects of ophthalmic clinicians.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

A clinical application study of digital manufacturing simple intraoral Gothic arch-tracing device in determining the centric relation of complete dentures / 北京大学学报(医学版)

OBJECTIVE@#To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration.@*METHODS@#Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not.@*RESULTS@#The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups.@*CONCLUSION@#The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.

Expression Profile and Clinical Significance of Cytokines and Chemokines in Patients with Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival.@*METHODS@#Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated.@*RESULTS@#Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05).@*CONCLUSION@#IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.