Characteristics of the chloroplast genome of Camellia insularis / 生物工程学报

In this study, the chloroplast genome of Camellia insularis Orel & Curry was sequenced using high-throughput sequencing technology. The results showed that the chloroplast genome of C. insularis was 156 882 bp in length with a typical tetrad structure, encoding 132 genes, including 88 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Codon preference analysis revealed that the highest number of codons coded for leucine, with a high A/U preference in the third codon position. Additionally, 67 simple sequence repeats (SSR) loci were identified, with a preference for A and T bases. The inverted repeat (IR) boundary regions of the chloroplast genome of C. insularis were relatively conserved, except for a few variable regions. Phylogenetic analysis indicated that C. insularis was most closely related to C. fascicularis. Yellow camellia is a valuable material for genetic engineering breeding. This study provides fundamental genetic information on chloroplast engineering and offers valuable resources for conducting in-depth research on the evolution, species identification, and genomic breeding of yellow Camellia.

Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid / 药学学报

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Efficacy of epithelial-off accelerated corneal cross-linking in the treatment of advanced keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of epithelial-off accelerated corneal cross-linking(CXL)in the treatment of advanced keratoconus.METHODS: A retrospective study was performed on data collected from 32 patients(43 eyes)with advanced keratoconus who underwent epithelial-off accelerated CXL at Ningxia Eye Hospital from April 2020 to December 2021. Slit-lamp, intraocular pressure, uncorrected visual acuity(UCVA), corrected visual acuity, specular microscope, Pentacam and Corvis ST were tested before and at 1, 3 and 6mo after surgery. Preoperative and postoperative corneal condition, UCVA, best corrected visual acuity(BCVA)and the values of corneal endothelial, maximum keratometry(Kmax), thinnest corneal thickness(TCT), anterior and posterior surfaces of the cornea K1, K2, biomechanically corrected intraocular pressure(bIOP), applanation time 1(A1T), applanation length 1(A1L), applanation velocity 1(A1V), applanation time 2(A2T), applanation length 2(A2L), applanation velocity 2(A2V), highest concavity deformation amplitude(HCDA), radius at highest curvature(HCR), highest concavity peak distance(HCPD)and stiffness parameter at first applanation(SP-A1)were recorded.RESULTS: There were differences between UCVA(LogMAR; 1.06±0.49, 0.78±0.39)and BCVA(LogMAR; 0.48±0.34, 0.38±0.29)before and at 6mo after surgery(P<0.05), but there were no differences in corneal endothelial cells(2917.39±288.38 vs. 2959.19±336.27 cells/mm2, P=0.477). There were differences among Kmax, TCT, anterior surface K1 and K2 and posterior surface K1 before and after surgery(P<0.05), and all increased at 1mo after surgery then returned to preoperative level at 3mo after surgery, while there was no difference in the posterior K2. Furthermore, there were statistical significance in A1T, HCPD and SP-A1 before and after surgery(P<0.05), while there were no statistical significance in A1L, A1V,A2T, A2L, A2V, HCDA, HCR and bIOP(P>0.05).CONCLUSION: Epithelial-off accelerated CXL can prevent the progression of keratoconus within half year after surgery, and it has certain safety.

Preliminary study on the material basis for expectorant and cough relief effects of the fruits of Phellodendron chinense var. glabriusulum Schneid / 中国药房

OBJECTIVE To explore the material basis and mechanism of expectorant and cough relief effects of the fruits of Phellodendron chinense var. glabriusulum Schneid. METHODS The expectorant and cough relief effects of volatile oil and water decoction of the fruits of P. chinense var. glabriusulum Schneid. were studied by ammonia water cough induction and drug expectorant model mice experiments； GC-MS and UPLC-MS technologies were used to identify its volatile oils and non-volatile components of the fruits of P. chinense var. glabriusulum Schneid. The active ingredients， core targets and pathways of expectoration and cough relief were analyzed by network pharmacology. RESULTS The volatile oil （0.8， 0.2 g/kg， calculated by volatile oil） and water decoction （12， 3 g/kg， calculated by crude drug） of the fruits of P. chinense var. glabriusulum Schneid. both had obvious expectorant and cough relief effects， and showed obvious dose-dependent relationship. A total of 38 volatile oil components were identified from the medicinal herbs， and the relative percentage contents of 8 components were greater than 1%， such as α -pinene， myrcene， β -caryophyllene， germanene D， isospathulenol； a total of 69 non-volatile oil components were identified， mainly including phenolic compounds， alkaloids， and flavonoids. The active ingredients screened from the identified components included 13 compounds such as α-pinene， myrcene， chlorogenic acid， luteolin， berberine. There were a total of 55 intersection targets with diseases， and the core targets were tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， vascular endothelial growth factor A （VEGFA）， serine/threonine kinase proteins （AKT1） and Toll-like receptor 4 （TLR4）. The molecular docking results showed that the active ingredients and the core targets had good binding ability. GO functional analysis found that the targets were significantly enriched in biological processes such as the reaction affecting lipopolysaccharides， the positive regulation of peptidyl serine phosphorylation， and the positive regulation of the biosynthesis process of nitric oxide. KEGG pathway enrichment analysis found that the targets were significantly enriched in the signaling pathways such as cancer， non-small cell lung cancer， proteoglycans in cancer. CONCLUSIONS Fruits of P. chinense var. glabriusulum Schneid. have obvious expectorant and cough relief effects， and its material basis may be α-pinene， myrcene， chlorogenic acid， luteolin， berberine， etc.， and mainly act on TNF， EGFR， VEGFA， AKT1， TLR4 and its significantly enriched signaling pathway.

Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Effect of Oleanolic Acid on Abnormal Water Metabolism of Mice with Water-dampness Retention Caused by Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the effect of oleanolic acid （OA） on water metabolism in mice with water-dampness retention caused by spleen deficiency and the mechanism. MethodThe 60 SPF Kunming （KM） mice were randomized into blank group （n=10） and modeling group （n=50）. Through long-term living in damp place and irregular diet， water-dampness retention caused by spleen deficiency was induced in modeling mice. Then the model mice were randomly classified into model group， natural recovery group， and low-dose， medium-dose， and high-dose OA groups. The mice in the blank group， model group， and natural recovery group were given （ig） 10 mL·kg-1·d-1 normal saline， and mice in the low-dose， medium-dose， and high-dose OA groups received 50， 100， 200 mg·kg-1·d-1 OA， respectively. The intervention lasted 7 days. Before and after modeling and administration， the general conditions of the mice were observed and body weight of mice was measured. The water content in feces and tissues was detected with the oven-drying method， and water load index and organ coefficient were measured with the weighing method. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the urinary D-xylose excretion， serum gastrin （GAS）， total protein （TP）， albumin （ALB）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， interleukin-6 （IL-6）， antidiuretic hormone （AVP）， aquaporin 1 （AQP1） in renal medulla， and liver Na+-K+-ATPase. At the same time， OA was docked with ALB， IL-6， AQP1， and Na+-K+-ATPase. ResultCompared with the blank group， the model group showed withered hair， emaciation， laziness， bradykinesia， slow weight growth， infrequent spontaneous activities， high water content in feces and tissues， low weight loss after water loading， high coefficient of each organ （P<0.05， P<0.01）. Moreover， the model group had less urinary D-xylose excretion， lower serum levels of GAS， TP， ALB， and HDL-C， higher levels of TC， LDL-C， AVP， and IL-6， lower expression of Na+-K+-ATPase in the liver， and higher expression of AQP1 in renal medulla than the blank group （P<0.05， P<0.01）. The three OA groups demonstrated better general conditions， faster weight gain， more frequent spontaneous activities， lower water content in feces and tissues， larger weight loss after water loading， and lower coefficient of each organ than the model group （P<0.05， P<0.01）. Moreover， compared with the model group， the three OA groups had high D-xylose excretion， high serum levels of GAS， TP， ALB， and HDL-C， low serum levels of TC， LDL-C， AVP， and IL-6， high expression of Na+-K+-ATPase in liver， and low expression of AQP1 in renal medulla （P<0.05， P<0.01）. The recovery in each OA group was better than that in natural recovery group. Molecular docking results also confirmed that OA had high binding affinity with ALB， IL-6， AQP1， and Na+-K+-ATPase. ConclusionOA can alleviate the abnormal water metabolism in mice with water-dampness retention caused by spleen deficiency， which lays a basis for its potential clinical application.

Study on quality standard for Miao medicine Clinopodium gracile / 中国药房

OBJECTIVE To establish the quality standard of Clinopodium gracile. METHODS Ten batches of C. gracile were collected to perform appearance and property identification， microscopic identification and thin layer chromatography （TLC） identification. Moisture， total ash， acid-insoluble ash and dilute ethanol extract were detected， and the content of rosmarinic acid was determined by HPLC. RESULTS The stem of C. gracile was slender， square columnar， covered by white fluff， the surface was grayish green or greenish brown； epidermal cells， non-glandular hairs， cortical cells and so on were seen in the cross section of the stem. Non-glandular hairs， ducts， wood fibers， mesophyll cells and so on could be seen in the powder. Results of TLC identification showed that there were spots of the same color in the chromatographic position corresponding to the chromatographic position of buddlejasaponin Ⅳb control. The contents of water， total ash， acid-insoluble ash， dilute ethanol extract and rosmarinic acid in 10 batches of samples were 8.69%-12.33%， 5.96%-13.33%， 0.14%-3.29%， 18.57%-32.61%， 0.35%-0.82%， respectively. The average values were 10.10%， 9.73%， 1.06%， 23.54% and 0.56%， respectively. CONCLUSIONS The established method can be used for quality control of C. gracile. It is preliminarily proposed that the ash content in the herb should not exceed 12.0%， the total ash content should not exceed 12.0%， the acid-insoluble ash content should not exceed 1.5%， the dilute ethanol extract should not be less than 18.0%， and the rosmarinic acid content should not be less than 0.45%.

Maternal liver damage induced by cadmium exposure in pregnant mice through hypoxia inducible factor-1α-mediated upregulation in DRP1 / 环境与职业医学

Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg−1), and a high-dose cadmium group (HCd group: 5 mg·kg−1). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl2) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl2 (10 μmol·L−1) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl2 (10 μmol·L−1) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl2 (10 μmol·L−1) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P＜0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P＜0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl2 for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.

Dental erosion caused by glucocorticoid therapy in a patient with optic neuritis: a case report / 华西口腔医学杂志

Dental erosion is characterized by progressively destroyed teeth, which has no relation to bacteria but to chemicals. Some internal factors, such as gastroesophageal reflux induced by bulimia, anorexia, gastrointestinal diseases, or drugs, and external factors, such as diet, drugs, and occupational acid exposure, are considered promotive factors for this disease. This article presents a patient suffering from severe dental erosion in the whole dentition, especially in the maxillary teeth, due to gastroesophageal reflux induced by glucocorticoid therapy for optic neuritis. This article discusses the mechanism between optic neuritis glucocorticoid therapy and dental erosion.

Current status and prospect of composite nano-phototherapy agents in the phototherapy for breast cancer treatment / 中国药房

As an adjuvant alternative therapy， phototherapy is widely used for early diagnosis and late treatment of breast cancer due to its non-invasive treatment characteristics. But the application of phototherapeutic agents has been limited in the clinic due to poor hydrophobicity and tissue targeting， low photostability， and obvious toxic side effects in vivo. With the development of nanotechnology， new composite nano-phototherapy agents have emerged. This paper summarizes the latest developments and findings of new composite nano-phototherapy agents for phototherapy in the field of breast cancer treatment in the past 5 years. With the development of multifunctional nanomaterials in the field of breast cancer imaging diagnosis and treatment， the modified phototherapy agent achieved further development respectively from improving light response to improve the light thermal conversion or increasing the generation of reactive oxygen species， targeting tumor microenvironment， immune cells and cancer cell surface receptors to achieve drug controllable response release， using biomimetic materials and endogenous substances to improve biocompatibility. Although phototherapeutic agents exhibit high cell-killing rates in the treatment of metastatic breast cancer models and effectively inhibit their recurrence and metastasis， problems remain regarding the safety and compatibility of synergistic therapy. Future studies can not only improve the existing effects of phototherapeutic agents， but also develop oral drugs with more convenient routes based on immunotherapy to amplify the immune response and resist breast cancer through multiple routes.

Changes in corneal biomechanics after small incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis evaluated by corneal visualization Scheimpflug technology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the changes in corneal biomechanics of patients with moderate refractive error after receiving small-incision lenticule extraction(SMILE)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)using the corneal visualization Scheimpflug technology(Corvis ST).METHODS:Prospective cohort study. A total of 65 moderate myopia patients(65 eyes)who were scheduled to undergo refractive surgery at the Ophthalmic Refractive Surgery Center of the Ningxia Eye Hospital from November 2020 to November 2021 were included in the study, and there were 30 eyes in the SMILE group and 35 eyes in the FS-LASIK group. The changes in corneal biomechanical parameters, including integrated radius(IR), inverse concave radius(ICR), deformation amplitude ratio 2mm(DAR2), stiffness parameter at first applanation(SP-A1), ambrosio relational thickness(ARTh)and the central curvature radius at highest concavity(HC-Radius)were observed by Corvis ST between both groups preoperatively and 1 and 3mo postoperatively.RESULTS: There were no statistical significance in biomechanical parameters between two groups of patients 1 and 3mo postoperatively(P&#x0026;#x003E;0.05). IR, ICR and DAR2 of each groups of patients 1 and 3mo postoperatively were significantly increased than those preoperatively, and SP-A1, ARTh and HC-Radius were significantly decreased than those preoperatively(all P&#x0026;#x003C;0.05). The biomechanical parameters at 1mo and 3mo postoperatively showed no statistical significance(P&#x0026;#x003E;0.05). In addition, a positive correlation was found between central corneal thickness(CCT)and ARTh and SP-A1 of the two groups of patients at 3mo postoperatively(FS-LASIK group: r=0.727, 0.819, SMLIE group: r=0.683, 0.434, all P&#x0026;#x003C;0.05), while a negative correlation was found between CCT and IR and ICR at 3mo postoperatively.(FS-LASIK group: r=-0.697, -0.622, SMLIE group: r=-0.447, -0.491, all P&#x0026;#x003C;0.05).CONCLUSION:For patients with moderate myopia, both SMILE and FS-LASIK can reduce corneal biomechanical stability. Both surgeries showed no significant differences in the effect on biomechanical, and the biomechanical has been stabilized at 1mo postoperatively. A correlation was found between postoperative CCT and ARTh, SP-A1, IR and ICR.

The risk factors of postoperative atrial fibrillation in critically ill lung surgery patients and the establishment of nomogram / 中华胸心血管外科杂志

Objective:To identify the risk factors of postoperative atrial fibrillation (POAF) in critically ill lung surgery patients and establish a nomogram.Methods:213 critically ill lung surgery patients were collected in Beijing Chaoyang Hospital from January 2018 to December 2021. Logistic analysis was used to analyze the risk factors of POAF. A nomogram was developed based on the verified risk factors. Results:The independent risk factors associated with POAF was mitral regurgitation ( OR=4.270, 95% CI: 1.380-13.213, P=0.012), cedilanid ( OR=14.619, 95% CI: 2.913-73.373, P=0.001), catecholamine ( OR=3.244, 95% CI: 1.144-9.203, P=0.027), pericardiotomy( OR=6.079, 95% CI: 1.362-27.128, P=0.009), systematic lymph node dissection( OR=5.460, 95% CI: 1.770-16.846, P=0.003). Nomogram model showed the ROC was 0.801(95% CI: 0.721-0.881, P<0.001). Conclusion:The risk factors of POAF in critically ill lung surgery patients are mitral regurgitation, cedilanid, catecholamine, pericardiotomy and systematic lymph node dissection. The nomogram predicted POAF better than other scoring systems.

Efficacy of first-line tyrosine kinase inhibitors plus immune checkpoint inhibitors in metastatic fumarate hydratase-deficient renal cell carcinoma / 中华泌尿外科杂志

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Visual analysis of research hotspots and trends of exercise therapy for hypertension in China based on CiteSpace and VOS viewer / 中华健康管理学杂志

Objective:To analyze the research hotspots and trends of exercise treatment of hypertension in China with bibliometrics software of CiteSpace and VOS viewer.Methods:The databases of CNKI, VIP, WanFang Data and the core collection of Web of Science were searched with the key words of exercise therapy, exercise intervention, exercise prescription, sports, movement, high blood pressure, hypertension, etc. Relevant periodical literature in Chinese and English were retrieved from the establishment of the databases to December 31, 2021. The CiteSpace and VOS viewer were used to perform visual analysis of the literature in the field of exercise therapy for hypertension in China.Results:A total of 1 507 literatures were included, including 1 430 in Chinese and 77 in English. In recent years, the number of studies on exercise treatment of hypertension in China showed a fluctuating upward trend. The research institutions were mainly universities and hospitals, high-yield institutions mainly included Beijing Sport University (20 articles), the First Affiliated Hospital of Nanjing Medical University (12 articles), the PLA General Hospital (13 articles) and Shanghai Sport University (11 articles). There was less cooperation between institutions and less cross-border cooperation. The proportion of sports and medical compound researchers in high-yield authors was relatively low (22.2%, 2/9). Keyword clustering could be summarized as three aspects: disease research, research objects and intervention methods. In terms of disease research, “pregnancy outcome”, “blood pressure”, “blood lipid” and “coronary heart disease” had strong burst (burst intensity 3.75, 3.70, 3.52, 3.12); in terms of research objects, “elderly patients” had the strongest burst (burst intensity 3.10); in terms of intervention methods, “exercise prescription”, “aerobic exercise” and “health education” had strong emergence (emergence intensity 6.08, 5.47, 4.01).Conclusions:Research achievements in the field of exercise therapy for hypertension in China are relatively rich in recent years. At present, the main research hotspots are disease research, research objects and intervention methods, and the integration degree of sports and medicine needs to be improved.

The status, problems and countermeasures of online teaching design and operation management in medical colleges: a case study of Harbin Medical University / 中华医学教育探索杂志

This paper first summarizes the cognition and understanding of online teaching, then introduces the active design and practice of online teaching in Harbin Medical University, and fully comprehends the quality of online teaching through the feedback to teachers and students. Through the investigation, the research group found that there are problems in online teaching, including teachers' difficulty in applying the teaching platform efficiently, limited Internet speed and hardware equipment, insufficient understanding and attention of individual teachers to online teaching, insufficient interaction between teachers and students, and difficulty in carrying out experiments and practical teaching. In this regard, the research group proposed countermeasures to change online teaching concept, reform online teaching methods, improve the function of online teaching platform, and optimize online course resources in order to timely summarize the online teaching situation, improve the shortcomings and promote advanced experience, and ensure the quality of follow-up online teaching.

Observation on the therapeutic efficacy and survival rate of oral Etoposide in children with disseminated medulloblastoma after the standard treatment plan / 中华实用儿科临床杂志

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Study on the molecular mechanism of Linggui Zhugan Decoction in treating hypertension and obesity based on network pharmacology and molecular docking technology / 国际中医中药杂志

Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.

Effect of self-made Bushen Jiangu Decoction combined with conventional western medicine therapy on the postoperative efficacy and bone transformation markers of osteoporotic vertebral compression fracture in the elderly / 国际中医中药杂志

Objective:To investigate the effect of self-made Bushen Jiangu Decoction on bone transformation markers in elderly patients with osteoporotic vertebral compression fracture after operation, and to evaluate the clinical efficacy.Methods:Prospective cohort study. A total of 92 patients with osteoporotic vertebral compression fracture after operation in Fangshan Hospital of Beijing University of Chinese Medicine from April 2020 to December 2021 who met the inclusion criteria were divided into 2 groups by random drawing method, with 46 in each group. The control group was treated with routine western medicine after operation, and the observation group was treated with self-made Bushen Jiangu Decoction on the basis of the control group. Both groups were treated for 3 months. TCM symptom scores were performed before and after treatment, and the prognosis of the patients was evaluated with the Chinese Osteoporosis Quality of Life (COQOL), VAS scale, and the Oswestry Dysfunction Index (ODI). The levels of amino terminal propeptide (PINP), cross-linked terminal peptide β special sequence (β-CTX) and bone morphogenetic protein 6 (BMP6) of type Ⅰ procollagen were determined by contrast chromogenic method with o-benzaldehyde. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:The total effective rate was 95.7% (44/46) in the observation group and 82.6% (38/46) in the control group, and there was a significant difference between the two groups ( χ 2=4.04 , P=0.044). After treatment, the scores of fracture nonunion, pain in back and loin, chilliness and lassitude, and pallor in the observation group were significantly lower than those in the control group ( t values were 4.84, 4.09, 4.87, 4.14, respectively, P<0.01). The scores of COQOL, VAS and ODI in the observation group were significantly lower than those in the control group ( t values were 6.26, 10.57 and 6.15, respectively, P<0.01). The levels of PINP [(44.93±5.86)μg/L vs. (49.76±6.02)μg/L, t=3.90] and β-CTX [(0.49±0.17) μg/L vs. (0.68±0.20) μg/L, t=4.91] in observation group were significantly lower than those in the control group after treatment ( P<0.05). The level of BMP6 [(81.23±9.14) μg/L vs. (75.14±8.25) μg/L, t=3.36] in observation group was significantly higher than that of the control group ( P<0.05). During the treatment,the incidence of adverse reactions in the observation group was 13.0% (6/46), while that in the control group was 8.7% (4/46), and there was no significant difference between the two groups ( χ 2=0.45, P=0.503). Conclusion:The self-made Bushen Jiangu Decoction combined with conventional western medicine therapy can adjust the level of bone transformation markers in elderly patients with osteoporotic vertebral compression fractures, improve the lumbar function and quality of life, and improve the clinical efficacy.

Evaluation of the effect of sham feeding on the recovery of gastrointestinal function after laparoscopic appendectomy based on an artificially intelligent bowel sound monitoring system / 国际外科学杂志

Objective:To explore and analyze the reliability and safety of sham feeding in facilitating the recovery of gastrointestinal function after laparoscopic appendectomy (LA), by using a new device, the Artificial Intelligence Bowel Tone Monitoring System.Methods:The data of 100 cases in Shaanxi Provincial People′s Hospital from Dec. 2020 to Sep. 2022 with acute appendicitis operated by LA who met the inclusion criteria. In this prospective study, participants were divided by random number table into a control group and an experimental group, with 50 cases in each group. The control group performed routine postoperative LA care, and the experimental group performed routine postoperative LA care and sham-feeding state care. The age, gender, recovery time of postoperative bowel sounds, time of first postoperative anal discharge, postoperative nausea and vomiting, abdominal distention, dry mouth and halitosis, and postoperative abdominal pain and other complications were recorded. GraphPad Prism 9.0 and SPSS 22.0 software were adopted to conduct data organization and analysis.Results:There were 100 valid cases in this trial. There were no statistical differences between the two groups in terms of gender, age, duration of surgery, abdominal pain and other symptoms ( P>0.05). The recovery time of bowel sounds after surgery was (8.92±0.56) h in the experimental group and (10.55±0.88) h in the control group, which was statistically significant ( t=10.99, P<0.0001); the recovery time of bowel sounds after surgery was (20.10±0.50) h in the experimental group and (20.96±0.59) h in the control group. There was a statistically significant difference between the two groups ( t=7.84, P<0.0001); there was a statistically significant difference between the experimental group (22%) and the control group (42%) for postoperative nausea and vomiting ( χ2=4.60, P=0.032); there was a statistically significant difference between the experimental group (16%) and the control group (52%) for postoperative abdominal distension ( χ2= There was a statistical difference between the experimental group (40%) and the control group (68%) ( χ2=7.89, P=0.005). The number of hospitalization days in the control group was (11.40±2.47) days and the days in the experimental group was (9.30±2.01) d, the difference between the two groups was statistically significant ( t=4.65, P<0.001); the hospitalization cost in the control group was (27 270.11±2 645.30) yuan and the cost in the experimental group was (23 669.68±2 841.28) yuan, the difference between the two groups was statistically significant ( t=6.56, P<0.001). Conclusion:To a certain extent, sham feeding can accelerate the recovery of gastrointestinal function in patients after LA, reduce the common postoperative discomfort, length of stay and hospital costs of patients.

LDHA inhibitor combined with targeted drugs synergistically inhibit the proliferation of fumarate hydratase-deficient renal cell carcinoma cells / 现代泌尿外科杂志

【Objective】 To explore the therapeutic effects of lactate dehydrogenase A (LDHA) inhibitor and targeted drugs on fumarate-hydratase-deficient renal cell carcinoma (FH-d RCC). 【Methods】 RNA-sequencing was used to detect the mRNA expression in FH-d RCC tissues, which was further validated with real-time fluorescence quantitative PCR and immunohistochemistry. Human-derived FH-d RCC cell line UOK262 and murine-derived FH-d RCC cell line FH1-/-CL19 (CL19) were treated with LDHA inhibitor [(R)-GNE-140] and listed kidney cancer targeted drugs (Axitinib, Cabozantinib, Sunitinib, Sorafenib, Pazopanib, Everolimus) respectively, and then treated with LHDA inhibitor in combination with the targeted drugs to observe the alteration of cell proliferation. The combination index (CI) of different dose groups of the combination drugs were analyzed with CompuSyn software to determine the optimal combination regimen. 【Results】 LDHA inhibitor and targeted drugs, including Cabozantinib, Sorafenib and Sunitinib, had a significant inhibitory effect on the proliferation of FH-d RCC cells, and the combination of Cabozantinib and Sorafenib or Pazopanib had a significant anti-tumor effect. 【Conclusion】 LDHA inhibitor combined with targeted drugs can significantly inhibit the growth of FH-d RCC cells, indicating that LDHA may be a potential therapeutic target of FH-d RCC.