Application value of bone cement containing rhbFGF and RHBMP-2 in PKP treatment of osteoporotic lumbar compression fracture / 中国骨伤

OBJECTIVE@#To investigate the effect of bone cement containing recombinant human basic fibroblast growth factor (rhbFGF) and recombinant human bone morphogenetic protein-2 (rhBMP-2) in percutaneous kyphoplasty(PKP)treatment of osteoporotic vertebral compression fracture(OVCF).@*METHODS@#A total of 103 OVCF patients who underwent PKP from January 2018 to January 2021 were retrospectively analyzed, including 40 males and 63 females, aged from 61 to 78 years old with an average of (65.72±3.29) years old. The injury mechanism included slipping 33 patients, falling 42 patients, and lifting injury 28 patients. The patients were divided into three groups according to the filling of bone cement. Calcium phosphate consisted of 34 patients, aged(65.1±3.3) years old, 14 males and 20 females, who were filled with calcium phosphate bone cement. rhBMP-2 consisted of 34 patients, aged (64.8±3.2) years old, 12 males and 22 females, who were filled with bone cement containing rhBMP-2. And rhbFGF+rhBMP-2 consisted of 35 patients, aged (65.1±3.6) years old, 14 males and 21 females, who were filled with bone cement containing rhbFGF and rhBMP-2. Oswestry disability index (ODI), bone mineral density, anterior edge loss height, anterior edge compression rate of injured vertebra, visual analog scale (VAS) of pain, and the incidence of refracture were compared between groups.@*RESULTS@#All patients were followed for 12 months. Postoperative ODI and VAS score of the three groups decreased (P<0.001), while bone mineral density increased (P<0.001), anterior edge loss height, anterior edge compression rate of injured vertebra decreased first and then slowly increased (P<0.001). ODI and VAS of group calcium phosphate after 1 months, 6 months, 12 months were lower than that of rhBMP-2 and group rhbFGF+rhBMP-2(P<0.05), bone mineral density after 6 months, 12 months was higher than that of rhBMP-2 and group calcium phosphate(P<0.05), and anterior edge loss height, anterior edge compression rate of injured vertebra of group rhbFGF+rhBMP-2 after 6 months and 12 months were lower than that of group rhBMP-2 and group calcium phosphate(P<0.05). There was no statistical difference in the incidence of re-fracture among the three groups (P>0.05).@*CONCLUSION@#Bone cement containing rhbFGF and rhBMP-2 could more effectively increase bone mineral density in patients with OVCF, obtain satisfactory clinical and radiological effects after operation, and significantly improve clinical symptoms.

Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Effect of Compatibility of Wujiwan on Pharmacokinetics and Tissue Distribution of Representative Components / 中国实验方剂学杂志

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L-1）， Coptidis Rhizoma group（B group， 38.4 g·L-1）， processed Euodiae Fructus group（C group， 5.88 g·L-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（Cmax） of Ber， Pal， Evo， and Rut were the highest and time to peak（tmax） were the lowest in the liver of A group. In plasma， the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group， tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver， compared with B-D groups， Cmax values of 5 representative components except Pae were elevated， AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t1/2） of each representative components in A group was elevated and tmax was decreased， and Cmax of each representative ingredient except Pal was decreased， AUC0-t values of Ber and Pal were increased， whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

FOXA1 in prostate cancer / 亚洲男科学杂志(英文版)

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

Investigation of pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm based on a "disease-syndrome-symptom-formula" association network analysis / 药学学报

Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.

Impact of sinonasal anatomic changes after endoscopic anterior skull base surgery on nasal airflow and air conditioning: a computational fluid dynamics study / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm-1 vs 0.32 (0.30, 0.38) mm-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (rs=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.

A comparative study for the efficacies of transaxillary non-inflatable endoscopic surgery versus traditional surgery for papillary thyroid carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ2=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.

Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

Prevalence of myopia among children and adolescents in Inner Mongolia Autonomous Region from 2019 to 2021 / 中国学校卫生

Objective@#To analyze the prevalence and trend of myopia among children and adolescents in Inner Mongolia from 2019 to 2021，so as to provide a reference for making scientific and effective prevention and controlling measures of myopia.@*Methods@#By using the stratified random cluster sampling method, 555 093 children and adolescents were selected from 12 professional institutions in league cities of the whole region for remote vision examination and refractive examination. The refraction test was carried out under the condition of non-Ciliary muscle paralysis using a desktop automatic computer optometer. Chi-squared test and multivariate Logistic regression were used to analyze the myopia status of children and adolescents and its influencing factors.@*Results@#From 2019 to 2021, the myopia rate of children and adolescents was 53.30%, 58.65% and 54.82%, respectively, the difference was statistically significant ( χ 2=991.70, P <0.01). The overall female myopia rate(58.82%) was higher than that of male (51.52%), and the differece was statistical significant ( χ 2=3 295.66, P <0.05). The myopia rates of boys and girls by year were 49.44% and 57.30%, 54.76% and 62.60%, 51.23% and 57.62%, respectively, and the differences were statistically significant ( χ 2=1 197.02, 922.31, 1 172.09, P <0.01). The overall myopia rate of urban students (59.42%) was higher than that of suburban counties (53.61%), and the difference was statistically significant ( χ 2=1 565.03, P <0.05). The myopia rates of children and adolescentss in urban and suburban counties were 59.20% and 50.79%, 60.26% and 57.88%, 58.95% and 53.36%, and the differences were statistically significant ( χ 2=1 150.80, 74.10, 529.25, P <0.01). The children and adolescents of learning stages were of statistical significance ( χ 2=92 402.39, P <0.05), and the overall myopia rate of senior school students was the highest, accounting for 83.57%. The difference of overall myopia rates of different age groups was of statistical significance ( χ 2=121 881.67, P <0.05), and the students in age group of 17 ranked the first (83.32%), those in age group of 5 ranked the last(15.52%).@*Conclusion@#From 2019 to 2021, the myopia rate of children and adolescents in the Inner Mongolia Autonomous Region increase first and then decrease, and the myopia rate in 2020 and 2021 is higher than that in 2019. The high incidence and low age of myopia are intensifying. The prevention and controlling of myopia among children and adolescents should be strengthened, so as to reduce the occurance of myopia.

Enzalutamide and olaparib synergistically suppress castration-resistant prostate cancer progression by promoting apoptosis through inhibiting nonhomologous end joining pathway / 亚洲男科学杂志(英文版)

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.

Traceability of Geographic Origin Using Human Skin and Oral Microbiota / 法医学杂志

OBJECTIVES@#To explore the possibility of using human skin and oral microorganisms to estimate the geographic origin of an individual through the sequencing analysis of bacterial 16S rRNA gene.@*METHODS@#Microbial DNA was extracted from the palm and oral microorganisms of the Han population in Shanghai and Chifeng, Inner Mongolia, and the composition and diversity of the microbiota were analyzed by full-length 16S rRNA gene sequencing. Then, differential species were screened and a geographic location prediction model was constructed.@*RESULTS@#The compositions of palm and oral microorganisms between Shanghai and Chifeng samples were both different. The abundance and uniformity of palm side skin microorganisms were higher in Chifeng samples than in Shanghai samples, while there was no significant difference in oral microorganisms. Permutational multivariate analysis of variance (PERMANOVA) confirmed that th e β -diversity between the samples from the two places were statistically significant, and the coefficients of determination (R2) for skin and oral samples were 0.129 and 0.102, respectively. Through principal co-ordinates analysis (PCoA), the samples from the two places could be preliminarily distinguished. The predictive model had the accuracies of 0.90 and 0.83 for the geographic origin using the skin and oral samples, respectively.@*CONCLUSIONS@#There are differences in the compositions of palm and oral microbiota between Han populations in Shanghai and Chifeng. The prediction model constructed by the random forest algorithm can trace the unknown individuals from the above two places.

Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Effectiveness and security of anisodine hydrobromide tablets in treating nonarteritic anterior ischemic optic neuropathy: a Chinese multicenter nonrandomized controlled study / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Machine Learning-based Identification of the Sites of DNA Double-Strand-Break in the Human Genome / 中国生物化学与分子生物学报

DNA double-strand break(DSB) is a serious form of DNA damage in cells, which is closely related to a variety of genomic instability diseases, including cancer, abnormal recombination and neuronal development. Due to the limitations of cost and technical threshold, high-resolution DSB mapping by high-throughput sequencing technology is very limited. This hinders our understanding of the DSB situation in the genomes of different species. Therefore, we developed a classification prediction model based on random Forest(RF), support vector machine(SVM) and logistic regression(LR) classifiers to predict DSB loci in the whole genome of human NHEK cells. In addition to the epigenetic features and DNA shape features commonly used in previous prediction studies, we found that DNA sequence features(kmer frequency, GC content, GC-skew, Mutual Information) can also characterize DSB sites. At the same time, the prediction accuracy is improved after considering DNA physical properties, chemical shifts and autocorrelation information. After combining all the above features, logistic regression(LR) has the best prediction performance(AUC = 0. 97), which is comparable to previous prediction(AUC = 0. 964). In addition, the optimal feature collection consisting of 294 features was obtained by the incremental feature search method, and the corresponding AUC value reached 0. 974.

Effect of Buyang Huanwu Decoction on cerebral ischemia-reperfusion injury in rats by regulating autophagy through PI3K/AKT pathway / 中国药理学通报

Aim To explore the effect of Buyang Huanwu Decoction on cerebral ischemia-reperfusion injury in rats by regulating autophagy through PI3K/AKT pathway. Methods The rats were randomly divided into five groups(n=10): sham operation group(Sham), model group(Model), Buyang Huanwu Decoction group(BYHWD), PI3K inhibitor group(LY294002)and Vehicle group(Vehicle). Except Sham group, the other groups were treated with 2h ischemia and 72 h reperfusion for modeling. The Zea Longa score was used to assess the neurological defects, HE was used to observe brain injury in the ischemic penumbra(IP), immunofluorescence was employed to detect LC3, and Western blot was used to detect pathway and autophagy marker proteins. Results Compared BYHWD group with model group, the neurological score of rats decreased, cerebral infarction volume decreased, the pathological lesions of brain IP were relieved, PI3K and p-AKT/AKT expression increased, and LC3Ⅱ/ decreased and p62 increased(P<0.05). The regulatory effect of BYHWD was weakened by LY294002(P<0.05). Conclusion Buyang Huanwu Decoction alleviates cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT pathway to inhibit autophagy.

Advances in the classification and treatment of isolated superior mesenteric artery dissection / 中华外科杂志

Isolated superior mesenteric artery dissection (ISMAD) has attracted more and more clinicians' attention in recent years. Patients onset of ISMAD often present with abdominal pain. The misdiagnosis or miss diagnosis is common because of the non-specific symptoms and signs, which even can endanger lives in serious cases. Imaging classification is of great significance for diagnosis and treatment of ISMAD. The Sakamoto classification and the Yun classification are two classical classified methods. However, with the further study of ISMAD, various new classifications emerge. Conservative treatment was once considered as the preferred. As the rapid development of endovascular therapy and the great progress of new devices, stenting therapy can significantly improve symptoms and achieve satisfactory long-term effects, and be even expected to become the preferred method for clinical therapy of ISMAD. However, the long-term effects of endovascular therapy still need a large number of follow-up data, and complications after stent implantation can't be ignored.

Risk factors of newly developed nonalcoholic fatty liver disease after pancreaticoduodenectomy / 中华外科杂志

Objective: To identify the risk factors of newly developed nonalcoholic fatty liver disease(NAFLD) after pancreaticoduodenectomy(PD). Methods: The clinical data of 130 patients who had undergone PD at Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School of Nanjing University from June 2018 to December 2020 were collected retrospectively. There were 74 males and 56 females, with age(M(IQR)) of 62(16) years (range: 22 to 84 years). Twenty-nine patients who developed NAFLD were divided into NAFLD group and 101 patients who did not suffer NAFLD were divided into no NAFLD group. Observation indications included:(1)preoperative demographics,intraoperative and postoperative characteristics; (2)the risk factors of newly developed NAFLD after PD. Count data were analyzed using χ2 test or Fisher's exact test. Measurement data were analyzed by student t test or Mann-Whitney U test. Multivariate analysis was performed using Logistic regression model with a stepwise forward approach. Results: All 130 patients successfully underwent PD and 29 cases(22.3%) developed NAFLD in 6 months after PD. The results of univariate analysis showed that gender,diabetic mellitus,the level of triglyceride preoperatively,and pancreatic ductal adenocarcinoma were the related factors of the development of NAFLD after PD(t=-2.655, χ²=4.563,U=-2.192,χ²=7.044;all P<0.05).Multivariate analysis revealed that gender,body mass index and pancreatic ductal adenocarcinoma were independent risk factors for the development of NAFLD after PD(OR=2.849,1.214,4.165,all P<0.05). Conclusion: Gender, body mass index and pancreatic ductal adenocarcinoma were independent risk factors for the development of NAFLD after PD.

Investigation on therapeutic potential and molecular mechanisms of Kunxian capsule against diabetic kidney disease via reversing the imbalance of "immune-inflammation" network / 药学学报

Drug repositioning provides new clinical indications for existing drugs. The imbalance between body's "immune-inflammation" regulation is one of the important factors in the occurrence and development of diabetic nephropathy (DN). Chinese patent medicine Kunxian capsule is clinically used for treating rheumatoid arthritis with satisfying immune-modulatory and anti-inflammatory actions. Notably, accumulating clinical evidence based on small cohorts had shown that Kunxian capsule may be used to treat DN. But the underlying pharmacological mechanisms remain unclear. Therefore, this study integrated "drug target-disease gene-biological pathway-function module" multi-level associated network analysis, and in vivo and in vitro experiments, to verify the pharmacological effects of Kunxian capsules in DN and to elucidate its molecular mechanisms. The experimental protocol was reviewed by the Laboratory Animal Welfare and Ethics Committee of China Academy of Chinese Medical Sciences, and it complies with the relevant regulations on laboratory animal welfare and ethics. As a result, the network analysis showed that the candidate targets of Kunxian capsule against DN were significantly involved into various functional modules which were related to modulation of immune-inflammation system, basement membrane lesion, abnormal hemorheology, energy metabolism and hormone metabolism, and the number of targets enriched by PI3K/AKT/NF-κB pathway is the largest. In addition, both in vivo and in vitro experiments demonstrated that Kunxian capsule by gavage effectively reduced blood glucose, improved insulin resistance, reduced blood lipid, inhibited renal extracellular matrix protein production and renal inflammation, improved renal function and pathological damages, and inhibited the activity of PI3K/AKT/NF-κB/TNF-α/IL-1β pathway in diabetic nephropathy rats. Collectively, these findings suggest the therapeutic potentials of Kunxian capsule to alleviate DN by regulating the imbalance of immune-inflammation system.

Recent progress of nanoparticle-enabled modulation of macrophages for cancer immunotherapy / 药学学报

Macrophages play an important role in maintaining homeostasis of the body, and they are also one of the most abundant immune cells in the tumor microenvironment (TME). These macrophages are often called tumor-associated macrophages (TAMs), which play an important role in the development of tumor and are an important target for tumor therapy. Studies have shown that tumor growth and metastasis can be inhibited by regulating the function of macrophages, but the therapeutic efficacy was often hampered by the poor performance of the drugs such as lack of targeting, poor solubility, low bioavailability, and severe side effects. After introduction of the background of macrophage and tumor therapy, this review focuses on the research progress of nano-drug delivery systems in the modulation of the function of macrophages to enhance tumor immunotherapy. Nano-drug delivery systems are diverse in structures and functions, and can regulate macrophage functions through a variety of mechanisms. Four important aspects of macrophage modulation, which included TAMs depletion, repolarization of TAMs, promoted phagocytosis of TAMs, and combinational modulation of TAMs were summarized. Each strategy together with typical examples was reviewed and future directions in this field were also prospected.

Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection / 中华心血管病杂志

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.