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.

Optimization of extraction technology of Guizhi shaoyao zhimu decoction / 中国药房

OBJECTIVE To optimize the e xtraction technology of Guizhi shaoyao zhimu decoction （GSZD）. METHODS The contents of 9 components in GSZD were determined by HPLC ，such as ephedrine hydrochloride ，pseudoephedrine hydrochloride ， mangiferin，paeoniflorin，liquiritin，5-O-methylvisammioside，glycyrrhizic acid ，cinnamic acid ，6-gingerol. On the basis of single factor experiment ，taking material-liquid ratio ，extraction times and extraction time as inspection factors ，taking the contents of above 9 components and the yield of dry extract as evaluation indicators ，the analytic hierarchy process and entropy weight method were used to determine the composite weight of each index and calculate the comprehensive score ；the extraction technology parameters of GSZD were optimized by Box-Behnken response surface method ，and the validation tests were conducted. RESULTS The composite weight of the contents of ephedrine hydrochloride ，pseudoephedrine hydrochloride ，mangiferin，paeoniflorin， glycyrrhizin，5-O-methylvisa- midol ，glycyrrhizinate，cinnamic acid ，6-gingerol and the yield of dry extract were respectively 0.12，0.10，0.05，0.12，0.14，0.06，0.13，0.15，0.10，0.03. The optimal extraction technology of GSZD is that the ratio of material to liquid is 1 ∶ 14（g/mL），extraction is 2 times，and the extraction time is 3.0 h；average comprehensive score of the 3 verification tests was 95.879，and RSD was 0.50％（n＝3），the deviation from the predicted comprehensive score （94.328）was 1.64％. CONCLUSIONS In this study ，the optimal extraction technology of GSZD is determined.

Relationship of learning burnout and subjective well-being of military medical university students and the mediating role of psychological capital / 第二军医大学学报

Objective To explore the effect of learning burnout on subjective well-being of military medical university students and the mediating role of psychological capital. Methods The learning burnout questionnaire, well-being scale and psychological capital scale were used to survey 796 military medical university students. The correlation of subjective well-being and psychological capital with learning bornout was analyzed. A intermediary function equation was established and the mediating effect of psychological capital was tested. Results The subjective well-being score of military medical university students was 4.42±0.77, psychological capital scale score was 4.48±0.67, and learning burnout score was 2.45±0.69. The subjective well-being, psychological capital and learning burnout scores were different among different grades, the subjective well-being scale and psychological capital scale scores of freshmen were significantly higher, and the learning burnout score was significantly lower than those of the junior students (tsubjective well-being=12.45, P<0.01; tpsychological capital=6.01, P<0.01; and tlearning burnout=-13.96, P<0.01). The learning burnout was negatively related to the subjective well-being and the psychological capital (r=-0.539, P<0.01, and r=-0.721, P<0.01). The psychological capital was positively related to the subjective well-being (r=0.596, P<0.01). The psychological capital had a partial mediating effect between learning burnout and subjective well-being, and the proportion of the mediating effect of total effect was 57.90%. Conclusion The subjective well-being not only can directly predict learning burnout of the students in military medical universities, but also indirectly predict the learning burnout through psychological capital. Improving subjective well-being of military medical university students is helpful for alleviating the learning burnout, and the mediating role of psychological capital should be emphasized at the same time.

Training approaches of data literacy for teachers, undergraduates, scientific researchers and librarians / 中华医学图书情报杂志

After the connotation of data literacy was elaborated, the status quo of domestic and foreign data literacy education was described, the training approaches of data literacy for teachers, undergraduates, scientific researchers and librarians were analyzed, and their characteristics and differences were compared in order to provide reference and lessons for building the data literacy education system and implementing the data literacy education.

Domestic and foreign hospital assessment systems and their problems / 中华医学图书情报杂志

The aims, indexes, methods, results, data sources, advantages and disadvantages of 12 domestic and foreign hospital assessment systems were analyzed and the problems in current hospital assessment were described in order to provide reference and lessons for perfecting the domestic hospital assessment systems.

Domestic and foreign hospital assessment systems and their problems / 中华医学图书情报杂志

The aims, indexes, methods, results, data sources, advantages and disadvantages of 12 domestic and foreign hospital assessment systems were analyzed and the problems in current hospital assessment were described in order to provide reference and lessons for perfecting the domestic hospital assessment systems.

Influence of CD133

Objective: To investigate the influence of CD133

Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes.</p><p><b>METHODS</b>We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients.</p><p><b>RESULTS</b>Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (β = 0.364, P = 0.001) and maximum pressure (β = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (β = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (β = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (β = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (β = 0.244, P = 0.014), and calluses over the course of the study.</p><p><b>CONCLUSIONS</b>We should pay attention to the BMI, HbA1c, cholesterol, ABI, SCV, and NSS changes in the process of preventing high plantar pressure and ulceration. Some associated precautions may be taken with the appearance of infections, blisters, and calluses.</p>

Predictive value of serum C-reactive protein for hospital death in patients with severe community-acquired pneumonia / 第二军医大学学报

Objective To evaluate the predictive value of serum C-reactive protein (CRP) for hospital death events in patients with severe community-acquired pneumonia (CAP). Methods The clinical data of 202 patients with CAP in Changhai Hospital and Second People's Hospital of Wuxi between Sep. 2006 and Sep. 2010 were retrospectively reviewed. The clinical and laboratory parameters, including the serum CRP level, white blood cell count, erythrocyte sedimentation rate (ESR) and serum creatine concentration were collected from Hospital Information System (HIS) and Laboratory Information System (LIS). The patients were divided into two groups according to the final death (CAP related complications) or survival of patients in the hospital. The receiver operating curve (ROC) analysis and multivariable logistical model were used to assess the predictive value of CRP on hospital death events. Results The median (interquartile range) serum CRP level of survival patients and patients who died during the hospital stay were 167. 00(132. 50,208. 50) mg/L and 327. 00(246. 25, 411. 50) mg/ L, respectively (Z= - 7. 481,P<0. 001). ROC analysis showed that CRP was an effective predictor for hospital death of CAP patients, with the area under curve (AUC) being 0. 85 (95%CI: 0. 78-0. 91). The optimal cot-off value for serum CRP was 230. 50 mg/L, with the sensitivity being 0. 83(95%CI: 0. 76-0. 89) and specificity being 0. 79(95%CI: 0. 65-0. 89). Logistic regression analysis showed that, after adjusted for age, serum creatinine and ESR, CRP on admission was still independently associated with hospital death of CAP patients (.OR = 13. 42, P<0. 01). Conclusion Increased CRP is an independent risk factor for hospital death events in patients with severe CAP.

Effect of Xuefu Zhuyu decoction in preventing complications of rib fracture in patients with blunt chest injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effect of Xuefu Zhuyu Decoction (XFZYD) on the incidence of complications of rib fracture in patients with blunt chest injury.</p><p><b>METHODS</b>One hundred and twenty patients with rib fracture stratified according to the AIS scale in three layers (1-3) were equally assigned to two groups, the treated group and the control group, all received conventional treatment, but XFZYD was administered to patients in the treated group additionally. The incidence of complications in patients, including atelectasis, pleural effusion, pulmonary contusion, pleurocentesis and closed thoracic drainage, were observed.</p><p><b>RESULTS</b>The incidence of pleural effusion in patients of AIS-1 and -2 in the treated group was 20% and 45% respectively, which was remarkable lower than that in the control group (55% and 85%) respectively (P < 0.05); in the treated group, 10% patients of AIS-3, for whom close thoracic drainage was applied, while in the control group, the percentage reached 60%, showing significant difference between groups (P < 0.05).</p><p><b>CONCLUSION</b>XFZYD could reduce the incidence of pleural effusion in patients with blunt chest injured rib fracture of AIS-1 or -2, and reduce the utilization of close thoracic drainage in those of AIS-3, so it is good for clinical practice.</p>

In-vitro amplification of oval cells with preservation of stem cell phenotype / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore cell culture techniques for amplification of oval cells with preservation simultaneously of the stem cell characteristics.</p><p><b>METHODS</b>Oval cell line OC3 was cultured in RPMI 1640 supplemented with 15% fetal bovine serum and 20 µg/L EGF. Cells were harvested every 5 passages and were examined with biomarkers including OV-6, c-kit, gamma-glutamyl transpeptidase, placental form of glutathione-S-transferase (GST-P), pyruvate kinase M₂, pyruvate kinase L and albumin using techniques including RT-PCR, immunocytochemistry, and enzymo-cytochemistry.</p><p><b>RESULTS</b>OC3 cell lines could be amplified abundantly in-vitro associating with expression of infant liver cell markers at various level, including OV-6, c-kit, gamma-glutamyl transpeptidase, GST-P, pyruvate kinase M₂, but no expression of mature hepatocyte markers detected including pyruvate kinase L and albumin.</p><p><b>CONCLUSIONS</b>Amplification of OC3 cells with preservation of the stem cell phenotype and high proliferation index can be achieved up to the 79(th) passages by culturing in RPMI 1640 supplemented with 15% fetal bovine serum and 20 µg/L EGF.</p>

Clinical and pathological analysis of chronic rejection following orthotopic liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestation and pathological features of chronic rejection (CR) and the management of CR after orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>From January 2004 to December 2006, there were 516 patients who had undergone OLT. All the clinical and pathological data were collected and retrospectively studied. Clinical manifestation, histopathological feature, diagnosis and anti-rejection treatment of CR were summarized and analyzed.</p><p><b>RESULTS</b>The incidence of CR was 2.3% (12/516), including 7 cases with early phases of CR and 5 cases with late phases of CR. The main pathological changes of CR were the vanishing bile duct syndrome and obliterative arteriopathy;and the early stage of CR were the damage of inter lobular bile duct, necrotic inflammation in central lobule, and inflammatory cells infiltration in portal area. Among 12 patients with CR, 7 cases with early CR were reversed by methylprednisolone (MP) pulse treatment and adjusting immunosuppressant dose, including 2 cases of whom were prescribed OKT3 treatment and 2 cases treated by ATG, and 5 cases with late CR underwent liver retransplantation (re-LT). Two patients died from infection, 1 case died from multiple organ failure in perioperative period after re-LT, another 2 cases were cured by re-LT, and the CR related mortality was 25.0% (3/12).</p><p><b>CONCLUSIONS</b>Chronic rejection following OLT is lack of typical clinical manifestation and pathological features, and the pathological changes can overlap and coexist. Post-transplant liver biopsy and graft specimen after re-LT is still "gold standard" to CR diagnosis. Some of early CRs can be reversed by early diagnosis and early treatment; for late CR recipient, re-LT should be considered.</p>

Clinical and pathological analysis of acute rejection following orthotopic liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute rejection is one of the most important factors for prognosis following liver transplantation. With the use of potent immunosuppressants, acute rejection does not always present typical manifestations. Moreover, other complications often occur concomitantly after liver transplantation, which makes early diagnosis of acute rejection more difficult. Acute rejection is best diagnosed by liver biopsy. Differentiation of clinical manifestations and pathological features plays an important role in achieving individualized immunosuppressive treatment and prolonging long term survival of patients given orthotopic liver transplants.</p><p><b>METHODS</b>From January 2004 to December 2006, 516 orthotopic liver transplantations were performed at the First Affiliated Hospital, Sun Yat-sen University. For patients who suffered acute rejection, clinical manifestations, histopathological features, diagnosis and anti-rejection treatment were summarized and analyzed.</p><p><b>RESULTS</b>In 86 cases (16.7%), of the 516 recipients, 106 episodes of acute rejection occurred, which included 9 with histopathological borderline changes, 36 Banff I rejections, 48 Banff II and 13 Banff III. Among these, 36 were cured by adjusting the dose of immunosuppressant and 65 were reversed by methylprednisolone pulse treatment. Five were methylprednisolone resistant, 3 of whom were given OKT3 treatment and 2 underwent liver retransplantation.</p><p><b>CONCLUSIONS</b>Due to potent immunosuppressive agents, acute rejection following an orthotopic liver transplantation lacks typical clinical manifestations and pathological features. Acute rejection is best diagnosed by liver biopsy. Designing rational individualized immunosuppressive regimen based on clinical and pathological features of acute rejection plays an important role in prolonging long term survival of patients.</p>

Lung cancer stem cells research. Clues from ontogeny

Cancer stem cell [CSC] hypothesis provides us with a new approach to the understanding of carcinogenesis, therapeutics, and prevention strategies. In recent years, the origin and biological characteristics of CSC were widely studied in solid tumors; it is astonishing to find out the delicate relevancy between CSC and committed progenitors evolved from embryonic stem cells [ESC] during organ development. In this review, we propose that some key molecular signal pathways during lung development are crucial for abnormal self-renewal and differentiation of lung cancer stem cell as well as try to elaborate the lung CSCs from the point view of ontogeny

Research on isolation and purification of total iridoid glycosides from herbal Lamiophlomis rotata / 中国中药杂志

<p><b>OBJECTIVE</b>Enriching the hemostatic active part total iridoid glycosides from the aqueous extract of herbal Lamiophlomis rotata.</p><p><b>METHOD</b>First derivative spectrophotometry was used as the detection method and the content of total iridoid glycosides was used as tracking target. The abilities of absorption and anti-absorption of ten different types of macroreticular resin were compared, after being used to absorb the iridoid glycosides from aqueous extract of herbal L. rotata. The best purification process was optimized.</p><p><b>RESULT</b>With the optimized purification process, the content of total iridoid glycosides was 67.53%.</p><p><b>CONCLUSION</b>XDA-1 macroreticular resin has good ability of absorption and anti-absorption for iridoid glycosides and 50% ethanol was the best solvent for anti-absorption. The macroreticular resin could be reused.</p>

Induced differentiation of rat hepatic oval cells in-vitro by combined hepatocyte growth factor and epidermal growth factor treatment / 中华病理学杂志

<p><b>OBJECTIVE</b>To characterize the biologic featrues of hepatic oval cells and their protein expression profiles during induced differentiation in vitro.</p><p><b>METHODS</b>Rat hepatic oval cells were treated with epidermal growth factor (EGF) and hepatocyte growth factor (HGF) in vitro, followed by morphological and molecular marker assessment by electromicroscopy, immunocytochemistry, RT-PCR and protein expression chip technology.</p><p><b>RESULTS</b>Ten weeks after induction, the levels of GST-P mRNA and M2-PK mRNA were significantly reduced, whereas those of ALB and CK18 were elevated. Significant variations of expression was seen in 8 protein species during the course of the induced differentiation.</p><p><b>CONCLUSION</b>Combined EGF and HGF treatment in vitro induces cell differentiation of hepatic oval cells, a process in which 8 protein species may play some regulatory roles.</p>

Capacitative Ca²⁺ entry is involved in ACh-induced distal colon smooth muscle contraction in rats / 生理学报

Contraction of smooth muscle cells is triggered by an increase in cytosolic Ca(2+) upon agonist stimulation. Ca(2+) influx across the plasma membrane constitutes a major component of the agonist-induced response in smooth muscle cells. Traditionally, voltage-operated Ca(2+) channel (VOCC) is considered as the channel mediating the Ca(2+) entry. However, this view has been challenged by recent discoveries, which demonstrated that other types of ion channels, such as store-operated and/or receptor-operated Ca(2+) channels (SOCC and/or ROCC), also participate in Ca(2+) response induced by agonists in smooth muscle cells. SOCC is defined as the channel activated in response to the depletion of the internal Ca(2+) stores, an event secondary to G protein coupled receptor or receptor tyrosine kinase stimulation. The Ca(2+) flow mediated by SOCC is termed as capacitative Ca(2+) entry (CCE). Previous study from other group has demonstrated that VOCC played a predominant role in ACh-induced contraction of distal colon smooth muscle in guinea pig. However, whether SOCC participates in the agonist-induced contractile response in this particular tissue is unknown. The present study was performed to investigate the role of CCE in ACh-induced mechanical activity of distal colon smooth muscle in rats. The contractile function of the smooth muscle was assessed by measuring isometric force of isolated rat distal colon rings. We showed that both high extracellular K(+) (40 mmol/L) and ACh (5 mumol/L) evoked striking contraction of the smooth muscle. The contractile responses were almost abolished by removal of extracellular Ca(2+) with ethylene glycol-bis(2-aminoethylether)-N,N,N',N' tetraacetic acid (EGTA), suggesting a critical contribution of extracellular source of Ca(2+) to the contraction. Verapamil (5 mumol/L), an L-type VOCC blocker, significantly attenuated, but didn't completely eliminate the high K(+)- and ACh-induced contraction (74% and 41% for high K(+) and ACh, respectively), indicating that additional channels might be involved in the contractile mechanism. Furthermore, ACh only induced transient contractions in the absence of extracellular Ca(2+). Readmission of Ca(2+) into the extracellular compartment resulted in a significant and sustained increase in the tension of the smooth muscle. This response was not affected by verapamil (5 mumol/L) and Cd(2+) (5 mumol/L), both of which efficiently block VOCC at the doses. However, La(3+), a known inhibitor of SOCC, significantly suppressed the Ca(2+) readdition-induced contraction in a dose-dependent manner. On the basis of these results, we conclude that contraction of smooth muscle in the distal colon is regulated by multiple Ca(2+) channels. In addition to VOCC-mediated Ca(2+) influx, SOCC-mediated CCE participates in agonist-induced contractile response of distal colon smooth muscle in rats.

Case Report of Peliosis Hepatic in Child and Its Literature Review / 实用儿科临床杂志

Objective To report a peliosis hepatic in child and review literature and discuss.Methods Case history was inquired.Physical,labtoratory,imagement and histopathology of liver biopsy(HE staining) were examed.Results A 4-year old girl appeared dermatitis with erythema and herpes at local skin where was bit by insect before onset.The girl appeared fever,cough,then abdominal pain,hepatomegaly,pleural effusion and ascites.Lab examination revealed slight elevation of aspartate transaminase,?-glutamyltranspeptidase and alkaline phosphatase.The liver B-mode ultrasonography and CT scan revealed hepatomegaly with density heterogeneity of the parenchyma.The liver biopsy revealed many small capsule filled with blood cells.Conclusions Clinical characteristics of the disease are fever,upper abdomen pain,janundice,ascites and hepatomegaly.The diagnosis shall be combined with the pathologic biopsy of liver.

Store-operated Ca2+ channels in rat colonic smooth muscle cells / 中国应用生理学杂志

<p><b>AIM</b>To study whether store-operated Ca2+ channel (SOC) is present in rat colonic smooth muscle cells.</p><p><b>METHODS</b>Intracellular Ca2+ ([Ca2+]i) changes induced by thapsigargin- or caffeine-activated SOC channel were measured in enzymatically dissociated rat colonic smooth muscle cells with the fluorescent indicator Fura-2/AM.</p><p><b>RESULTS</b>In the absence of external Ca2+ , the sarco-endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (1 micromol/L) and ryanodine receptor (RyR) activator caffeine both transiently elevated [Ca2+]i from (68.32 +/- 3.43) nmol/L to (240.85 +/- 12.65 ) nmol/L, (481.25 +/- 34.77) nmol/L. A subsequent reintroduction of Ca2+ into the extracellular solution resulted in [Ca2+]i further elevated to (457.55 +/- 19.80) nmol/L, (1005.93 +/- 54.62) nmol/L; (643.88 +/- 34.65) nmol/L, (920.16 +/- 43.25) nmol/L, respectively. And the elevated response was blocked by lanthanum (1 mmol/L), but was insensitive to L-type voltage calcium channels blocker verapamil and membrane depolarization.</p><p><b>CONCLUSION</b>SOC activated by store depletion are present in rat colonic smooth muscle cells. And we further prove the existence of such Ca2+ channels in excitable cells.</p>

Effects of enhanced external counterpulsation in atherosclerosis and NF-kappaB expression: a pig model with hypercholesterolemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the effects of enhanced external counterpulsation (EECP) on the vascular morphology, and endothelial function using experimentally induced hypercholesterolemic pigs.</p><p><b>METHODS</b>Thirty five male pigs were randomly divided into three groups: 7 normal control animals, 11 hypercholesterolemic animals, and 17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured. The coronary arteries and aortas were sampled for histopathologic and ultrastructural examination. The NF-kappaB protein expression of porcine coronary arteries was investigated by immunofluorescence.</p><p><b>RESULTS</b>Compared with the normal controls, serum cholesterol levels were significantly higher in the hypercholesterolemic animals with or without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP [(3.33 +/- 2.40)%, versus (12.03 +/- 7.12)% in those without EECP, P < 0.05]. Lipid deposition, endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those not. Moreover, activation and expression of NF-kappaB also decreased significantly (P < 0.05) in animals receiving EECP.</p><p><b>CONCLUSIONS</b>EECP improves the morphology and function of vascular endothelium, and retards the development and progression of atherosclerosis, likely through the inhibition of NF-kappaB signaling pathway.</p>