Research progress on biomarkers of pseudoexfoliative glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Pseudoexfoliative glaucoma(PEXG)is an eye disease that seriously endangers vision. It is more invasive than primary open-angle glaucoma(POAG), with more serious damage to the optic nerve, worse prognosis and higher resistance to treatment. Early diagnosis of PEXG can help to treat the disease in time and delay the progress of the disease, so it is important to determine appropriate biomarkers. In recent years, more and more people have begun to study the biomarkers of PEXG, hoping to understand the pathogenesis of the disease, find out the potential early diagnosis and treatment targets of PEXG, and provide some help to the disease through the research of genomics, transcriptomics, proteomics, metabolomics and lipomics markers. This article will review the progress of biomarkers of PEXG in recent years, some biomarkers may provide new ideas for early diagnosis of PEXG in the future.

Analysis of the pathogenesis and risk factors of gallstone / 中华外科杂志

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ2 test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ2=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ2=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m2(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.

Advance on nitric oxide combined photothermal therapy for tumor treatment / 药学学报

Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.

Construction and validation of a simple model for predicting the risk of prenatal depression / 四川精神卫生

BackgroundMental illness during pregnancy has become a major public health problem in China over the recent years， and depression is the most common psychological symptom during pregnancy. Current research efforts are directed towards the therapy on prenatal depression， whereas the construction of prediction model for prenatal depression risk has been little studied. ObjectiveTo construct a simple model for predicting the risk of prenatal depression， thus providing a valuable reference for the prevention of maternal depression during pregnancy. MethodsA total of 803 pregnant women attending three hospitals in Nanchong city were consecutively recruited from May 2021 to February 2022. A self-administered questionnaire was developed for the assessment of social demographic variables， obstetrical and general medical indexes and psychological status of all participants， and Self-rating Depression Scale （SDS） was utilized to screen for the presence of maternal depression. Subjects were randomly assigned into modelling group （n=635） and validation group （n=168） at the ratio of 8∶2 under simple random sampling with replacement. The candidate risk factors of maternal depression during pregnancy were screened using binary Logistic regression analysis， and the predictive model was constructed. Then the performance of the predictive model was validated using receiver operating characteristics （ROC） curve. Results① Lack of companionship （β=-0.692， OR=0.501， 95% CI： 0.289~0.868）， low mood during the last menstrual period （β=-1.510， OR=0.221， 95% CI： 0.074~0.656）， emotional stress during the last menstrual period （β=-1.082， OR=0.339， 95% CI： 0.135~0.853）， unsatisfactory relationship between mother-in-law and daughter-in-law （β=-1.228， OR=0.293， 95% CI： 0.141~0.609）， and indifferent generally relationship between mother-in-law and daughter-in-law （β=-0.831， OR=0.436， 95% CI： 0.260~0.730） were risk factors for prenatal depression in pregnant women （P<0.05 or 0.01）. ② Model for predicting the prenatal depression risk yielded an area under curve （AUC） of 0.698 （95% CI： 0.646~0.749）， the maximum Youden index was 0.357 in modelling group with the sensitivity and specificity was 0.606 and 0.751， and an AUC of 0.672 （95% CI： 0.576~0.767） and maximum Youden index of 0.263 in validation group with the sensitivity and specificity of 0.556 and 0.707. ConclusionThe simple model constructed in this study has good discriminant validity in predicting of the risk of prenatal depression. ［Funded by Nanchong Social Science Research Project of the 14th Five-Year Plan （number， NC21B165）］

Effectiveness of HPV vaccines in real-world study / 中华微生物学和免疫学杂志

Human papillomavirus (HPV) is an epitheliotropic virus. High-risk HPV infections lead to precancerous lesions which may progress to cancer in the cervix, vagina and vulva, while low-risk HPV infections cause benign lesions such as genital warts and recurrent respiratory papillomas. HPV infection remains one of the major public health problems threatening human health. To date, six prophylactic preventive HPV vaccines have been licensed, and the effectiveness of HPV vaccination has gradually appeared in some countries with earlier vaccination. HPV vaccination has been proved to be effective in protecting against diseases related to HPV infection, which leads to significant reductions in the incidence of vaccine-type HPV-related infection, high cervical lesions, anogenital warts, recurrent respiratory papillomatosis and other relevant diseases. The herd protection effect of the vaccines is outstanding. Meanwhile, a bivalent HPV vaccine has been demonstrated for the cross-protection against HPV infections of non-vaccine types (HPV31/33/45) in real-world vaccination practice.

Clinical diagnostic techniques for rare genetic diseases in children: current status, advances, and thoughts / 中国当代儿科杂志

Rare diseases refer to a group of single diseases with low incidence rates, complex pathogeneses, severe disease conditions, and rapid progression. Most rare diseases have a genetic background and may occur in childhood. Paying attention to the rare genetic diseases in children and performing early diagnosis and treatment can effectively delay the course of disease and improve the quality of life of children. Many rare diseases can be diagnosed with the help of various experimental techniques, but the diagnosis of rare diseases is still not widely understood. This article summarizes the laboratory diagnostic techniques currently used for rare genetic diseases in children, so as to provide clues for the diagnosis and treatment of such diseases and help to enhance the theoretical understanding and precise medical treatment of rare genetic diseases in children.

Free energy perturbation (FEP)-guided scaffold hopping

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG MM-PBSA or ΔG MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

Anthrahydroquinone-2,6-disulfonate alleviates paraquat-induced kidney injury via the apelin-APJ pathway in rats

Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

Anthrahydroquinone-2,6-disulfonate alleviates paraquat-induced kidney injury via the apelin-APJ pathway in rats

Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

Mechanism of blood brain barrier in the pathogenesis and therapeutics of multiple sclerosis / 中华神经科杂志

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.

Efficacy of fractional CO 2 laser and 1064-nm, Q-switched Nd∶YAG laser on xanthelasma palpebrarum / 中华医学美学美容杂志

Objective:To determine the clinical efficacy and safety of a fractional CO 2 laser and a 1 064 nm, Q-switched Nd∶YAG laser therapy in the treatment of xanthelasma palpebrarum. Methods:From October 2020 to October 2021, 30 patients (5 males and 25 females) with bilateralxanthelasma palpebrarum of the eyelid were enrolled in the Department of Dermatology, the First Affiliated Hospital of Xiamen University. The age ranged from 38 to 67 (51±7) years. One side was randomly treated with fractional CO 2 laser as the fractional group, and the other side was treated with Q-switch 1 064 nm Nd∶YAG laser as the Q-switch group. The treatment was given every 28 days for 4 times. Before treatment and 1 month after the last treatment, the general pictures were taken to compare the clinical effect. Skin ultrasound was used to measure the difference of tumor thickness before and after treatment. The incidence of adverse reactions, such as local scar, hyperpigmentation or hypopigmentation after inflammation, were recorded. Results:Under general photos, there was statistically significant difference in efficacy scores between the two groups before and after treatment ( Z=-3.082, P<0.05). By comparison of tumor thickness under skin ultrasound, the difference between the two groups before and after treatment was statistically significant ( t=21.60, P<0.05; t=17.29, P<0.05); there was no statistically significant difference between the two groups before treatment ( t=0.46, P=0.650), but there was statistically significant difference between the two groups after treatment ( t=8.41, P<0.001). No serious adverse reactions occurred in both groups. Conclusions:Fractional CO 2 laser or Q-switch 1 064 nm Nd∶YAG laser can safely and effectively improve xanthelasma palpebrarum, in which the effect of fractional CO 2 laser is much better.

Quality value transfer of substance benchmarks in Sanpian Decoction / 中国中药杂志

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans

Despite the success of SARS-CoV-2 vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of COVID-19. Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct non-overlapping epitopes on the spike protein receptor binding domain to potently neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and abrogate effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry. Together, these two mAbs create a higher barrier to viral escape and a wider breadth of coverage, neutralizing all known SARS-CoV-2 variants of concern. In a non-human primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, while therapeutic administration accelerated virus clearance from lung. In an ongoing Phase I study in healthy participants (NCT04507256), 300 mg intramuscular AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers >10-fold above those of convalescent sera for [≥]3 months, which remained 3-fold above those of convalescent sera 9 months post-AZD7442 administration. Approximately 1-2% of serum AZD7442 levels were detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentrations suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.

Study of occult uterine perforation in brachytherapy of cervical cancer / 中华放射肿瘤学杂志

Objective:To evaluate the difference of dosimetry between three-dimensional and two-dimensional plans based on CT images of occult perforation in brachytherapy of cervical cancer, aiming to provide clinical reference.Methods:A total of 817 patients with cervical cancer received simple intrauterine (intrauterine tandem plus vaginal colpostats) three-dimensional brachytherapy in Chongqing University Cancer Hospital from January 2019 to December 2020 were retrospectively reviewed. Among them, 16 patients had occul uterine perforation. Based on Oncentra Brachy Therapy plan system, the single prescription dose was 6Gy. Three-dimensional (3D group) and two-dimensional (2D group) plans were designed on the perforated CT images The target volume, conformal index (CI), conformal index coformity index (COIN) and organs-at-risk (OAR) D 2cm 3 parameters were used to assess the plans between two groups. Results:The incidence of pccult uterine perforation was 1.96%(16/817) during brachytherapy for cervical cancer. The volume of prescription dose curve in the 3D group was (40.74±14.98) cm 3, significantly smaller compared with (91.46±19.71) cm 3 in the 2D group ( P<0.05), whereas the volume of the high-risk clinical target area wrapped by prescription dose curve did not significantly differ between two groups ( P>0.05). The CI and COIN in the 3D group were 0.79±0.10 and 0.72±0.96, significantly higher compared with 0.38±0.09 and 0.37±0.18 in the 2D group (both P<0.05). The D 2cm 3 of bladder, rectum, sigmoid colon, small intestine in the 3D group were (306.06±77.57) cGy, (252.27±72.60) cGy, (127.25±62.84) cGy and (228.79±94.90) cGy, significantly lower than (548.03±164.21) cGy, (411.16±118.74) cGy, (227.45±94.48) cGy and (450.95±157.96) cGy in the 2D group (all P<0.05). Conclusions:Application of image guidance in brachytherapy of cervical cancer is helpful to detect occult uterine perforation. When occult uterine perforation occurs, the use of three-dimensional plan can basically meet the clinical needs, which is significantly better than the two-dimensional plan.

Changes of corneal anterior surface morphology and higher-order aberrations after Smart / 中华实验眼科杂志

Objective:To compare the changes of corneal asphericity and higher-order aberrations after smart pulse technology-assisted transepithelial photorefractive keratectomy (Smart) for low and moderate myopia and to investigate the changes in the shape of the front corneal surface in patients with different diopters.Methods:A non-randomized controlled study design was used.Ninety-eight eyes of 54 patients with moderate or low myopia who underwent Smart surgery in Tianjin Medical University Eye Hospital from November 2018 to March 2019 were included.The 41 eyes of 23 patients with low myopia were set as the low-myopia group, and 57 eyes of 31 patients with moderate myopia were assigned as the moderate-myopia group.The Pentacam anterior segment analysis system was used to measure Q value, index of surface variance (ISV), corneal higher-order aberration (HOA), corneal vertical coma (Z 3-1), corneal horizontal coma (Z 31) and spherical aberration (Z 40) before surgery, 1 month and 3 months after surgery.The anterior surface morphology was compared between the low-myopia and moderate-myopia group.Pearson correlation analysis was used to analyze the correlations between measurement parameters.The study protocol was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2019KY-17). Written informed consent was obtained from each patient before surgery. Results:Corneal Q value, ISV, HOA and Z 40 were 0.445±0.191, 26.973±5.611, 0.671±0.142 and 0.384±0.188, respectively, in the low-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.273±0.817, 13.784±2.376, 0.433±0.687 and 0.231±0.062 (all at P<0.05). Corneal Q value, ISV, HOA and Z 40 were 0.693±0.203, 34.038±5.773, 0.874±0.216 and 0.520±0.129, respectively, in the moderate-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.309±0.104, 14.838±3.992, 0.409±0.081 and 0.228±0.089 (all at P<0.05). Corneal Q values, ISV, HOA and Z 40 in the moderate-myopia group were higher than those in the low-myopia group at different time points after surgery, showing significant differences between the two groups (all at P<0.05). There was no significant difference in postoperative 1-month and 3-month corneal Z 3-1 and Z 31 between the two groups (both at P>0.05). The results of correlation analysis showed that there were no significant differences in ΔQ value and ΔISV between the two groups, both of which were negatively correlated with spherical equivalent (ΔQ value: low-myopia group: r=-0.364, P=0.044; moderate-myopia group: r=-0.589, P<0.01; ΔISV: low-myopia group: r=-0.298, P=0.039; moderate-myopia group: r=-0.409, P=0.022). ΔQ value and ΔZ 40 were positively correlated in the moderate-myopia group ( r=0.348, P=0.009); there was no significant correlation between ΔQ value and ΔZ 40 in the low-myopia group ( r=0.180, P=0.266). Conclusions:The corneal high-order aberrations and ISV after Smart are increased in comparison with preoperative values in the low-myopia and moderate-myopia eyes, and the corneal Q values change from negative to positive.The effect of Smart on corneal asphericity is less in the low-myopia eyes.

Analysis on quality value transmitting of substance benchmark of Houpo Wenzhong Decoction / 中国中药杂志

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.

Mechanism of Jinqi Jiangtang Tablets in treatment of pancreatic β cell dysfunction based on network pharmacology and molecular docking technology / 中国中药杂志

The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic β cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic β cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic β cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic β cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, β-carotene and β-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic β cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic β cell dysfunction.

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the -helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.

Gene Mutation Spectrum of Thalassemia Among Children in Yunnan Province.

Background: Thalassemia is an autosomal genetic disorder, found throughout the world. It is still not treatable and create socio economic problems. In this study, we investigated the prevalence and spectrum features of thalassemia in Yunnan Province, the southwestern area of China. During 2014-2018, a total of 3,539 suspected thalassemia children were detected with α- and ß-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Kunming Children's Hospital. Results: Of these patients, 1,130 were diagnosed thalassemia gene carriers with a carrying rate of 31.92%. Among them, α-thalassemia was 43.63%, ß-thalassemia was 53.98%, cases with both α- and ß- thalassemia was 2.39%. In α-thalassemia patients, the most common mutations was -SEA/αα (52.13%), followed by -α3.7/αα (27.79%), hemoglobin H disease (18.46%), and -α4.2/αα (1.62%). Fifteen gene mutations and 30 genotypes were identified in ß-thalassemia patients, with the five most common mutations CD17 (A>T) (29.51%), CD41-42 (-TTCT) (27.87%), IVS-II-654 (C>T) (14.92%), CD26 (G>A) (6.89%), and CD26/CD27 (2.62%) accounting for 81.81% of the ß-globin gene mutations. Furthermore, we founded two rare mutations CD34 (TGG → TAG) and Int in Chinese populations. Conclusions: Our results suggested that the prevalence and gene mutation spectrum of thalassemia display obviously heterogeneity among children in Yunnan Province. The findings provide the valuable information for premarital and pre-pregnancy screening, prenatal diagnostic services, and designing appropriate prevention programs to control thalassemia for future in this area.