Neuronal lack of PDE7a disrupted working memory, spatial learning, and memory but facilitated cued fear memory in mice.

BACKGROUND: PDEs regulate cAMP levels which is critical for PKA activity-dependent activation of CREB-mediated transcription in learning and memory. Inhibitors of PDEs like PDE4 and Pde7 improve learning and memory in rodents. However, the role of PDE7 in cognition or learning and memory has not been reported yet. METHODS: Therefore, we aimed to explore the cognitive effects of a PDE7 subtype, PDE7a, using combined pharmacological and genetic approaches. RESULTS: PDE7a-nko mice showed deficient working memory, impaired novel object recognition, deficient spatial learning & memory, and contextual fear memory, contrary to enhanced cued fear memory, highlighting the potential opposite role of PDE7a in the hippocampal neurons. Further, pharmacological inhibition of PDE7 by AGF2.20 selectively strengthens cued fear memory in C57BL/6 J mice, decreasing its extinction but did not affect cognitive processes assessed in other behavioral tests. The further biochemical analysis detected deficient cAMP in neural cell culture with genetic excision of the PDE7a gene, as well as in the hippocampus of PDE7a-nko mice in vivo. Importantly, we found overexpression of PKA-R and the reduced level of pPKA-C in the hippocampus of PDE7a-nko mice, suggesting a novel mechanism of the cAMP regulation by PDE7a. Consequently, the decreased phosphorylation of CREB, CAMKII, eif2a, ERK, and AMPK, and reduced total level of NR2A have been found in the brain of PDE7a-nko animals. Notably, genetic excision of PDE7a in neurons was not able to change the expression of NR2B, BDNF, synapsin1, synaptophysin, or snap25. CONCLUSION: Altogether, our current findings demonstrated, for the first time, the role of PDE7a in cognitive processes. Future studies will untangle PDE7a-dependent neurobiological and molecular-cellular mechanisms related to cAMP-associated disorders.

Application of holographic image technology in intracranial tumor surgery / 肿瘤研究与临床

Objective:To explore the feasibility and clinical value of holographic image technology in intracranial tumor surgery.Methods:A total of 40 patients with intracranial tumors in Beijing Tiantan Hospital, Capital Medical University from November 2020 to March 2021 were randomly divided into the experimental group (20 cases) and the control group (20 cases) based on the random number table. Patients in the experimental group underwent craniotomy assisted by holographic technology, while patients in the control group underwent conventional craniotomy. The Karnofsky performance status scores of patients before the operation and 7 days after the operation were recorded, and the self-rating anxiety scale was applied to evaluate the anxiety of the patients' families.Results:The head CT 12 h after surgery showed no tumor cavity hyperdensity in all patients. The head magnetic resonance imaging (MRI) 72 h after surgery revealed 17 cases of total resection and 3 cases of subtotal resection in the experimental group; in the control group, there were 16 cases of total resection and 4 cases of subtotal resection. In the experimental group, 1 patient's left lower limb muscle strength was grade Ⅱ after the operation and recovered to grade Ⅴ-at discharge. In the control group, the left limb muscle strength of 2 patients was grade Ⅲ after the operation and recovered to grade Ⅴ at discharge. The patients with Karnofsky scores of 60, 70, 80, 90, 100 scores were found in 1 case, 5 cases, 8 cases, 6 cases, 0, respectively of the experimental group and 0, 4 cases, 9 cases, 6 cases, 1 case, respectively of the control group before the operation, and the difference was statistically significant ( P > 0.05); the patients with Karnofsky scores of 50, 60, 70, 80, 90, 100 scores were found in 1 case, 0, 0, 7 cases, 9 cases,3 cases, respectively of the experimental group and 0, 3 cases, 6 cases, 4 cases, 5 cases, 2 cases, respectively of the control group after the operation, and the difference was statistically significant ( P = 0.018). The difference of Karnofsky score before and after the operation in the experimental group was statistically significant ( P = 0.029), while there was no statistically significant difference in the Karnofsky score before and after the operation in the control group ( P = 0.241). There were 8 cases, 9 cases, 2 cases and 1 case of non-anxiety, mild anxiety, moderate anxiety, severe anxiety, respectively in the experimental group and 3 cases, 4 cases, 8 cases and 4 cases of non-anxiety, mild anxiety, moderate anxiety, severe anxiety, respectively in the control group before the operation; there were 9 cases, 9 cases, 2 cases and 0 case of non-anxiety, mild anxiety, moderate anxiety, severe anxiety, respectively in the experimental group and 2 cases, 5 cases, 9 cases and 4 cases of non-anxiety, mild anxiety, moderate anxiety, severe anxiety, respectively in the control group after the operation. The preoperative and postoperative anxiety scores of the experimental group were all lower than those of the control group, and the differences were statistically significant (preoperative P = 0.016,postoperative P = 0.002). Conclusions:Holographic technology can assist in formulating an accurate surgical plan before intracranial tumor surgery, intuitively display the anatomical relationship between the tumor and its surrounding important tissues during operation, reduce the surgical side injuries and decrease the anxiety of the patients' family.

The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华外科杂志

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9th to <10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Discussion on the use of occupational contraindication cardiovascular disease in Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) / 中华劳动卫生职业病杂志

Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) has played an important role in screening occupational contraindications and preventing occupational diseases since its implementation. However, during the use of occupational health examination, we found that the use of occupational contraindication on cardiovascular disease was not "homogenized" due to the differences in the understanding of various physical examination institutions. Therefore, this paper mainly discussed the connotation and quantitative standards of organic heart disease, arrhythmia, hypertension in the occupational contraindication cardiovascular disease in the specification for "homogenization".

Advances in tumor regression patterns and safe distance of distal resection margin after neoadjuvant therapy for rectal cancer / 中华胃肠外科杂志

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.

Case report of habitual dislocation of the hip in children and a review of systematic literature / 中华骨科杂志

Objective:To explore the clinical effect of observation and psychological intervention, splint or brace fixation as well as surgical treatment on habitual dislocation of the hip (HDH) and to combine the authors' data with a compilation of the cases from the literature, evaluingating the epidemiological characteristics of HDH and the treatment scheme to maintain the stability of hip joint by systematic literature review in children.Methods:A retrospective analysis of the relevant data of 11 patients (12 hips) with HDH were treated from March 2007 to March 2021, including 2 boys and 9 girls. The age of the first dislocation was 2.25 (1.66, 3.75) years old and 4.33 (3.33, 6.17) years old at the age of diagnosis. At the same time, the relevant literature reports were searched from 1932 to 2022, and 24 HDH patients reports and clinical studies were confirmed to be included in this study according to the inclusion and exclusion criteria. The data of 33 patients (38 hips) with HDH who were obtained in the literature, including 5 boys and 28 girls. The age of the first dislocation was 2.00 (1.50, 2.00) years old and 4.00 (2.55, 5.00) years old at the age of diagnosis. A total of 44 patients (50 hips) with HDH who were analyzed, including gender, age of first dislocation, age of diagnosis, mode of stimulating dislocation, side and direction of dislocation, accompanying symptoms, family history, trauma history and imaging examination. The data of 41 patients with HDH (3 patients were excluded due to lack of treatment description) were treated with observation and psychological intervention in 19 patients, splint or brace fixation in 13 patients, and surgical treatment in 9 patients. The femoral neck-stem angle, acetabular index, central edge angle (CE angle) and Reimers instability index were measured by AutoCAD software, and the hip function was evaluated by Harris standard. Meantime, the disappearance time of dislocation was recorded.Results:The average follow-up time of 44 patients (50 hips) with HDH were 4.05±2.93 years old, and the time of disappearance of dislocation after treatment were 1.28±1.19 years old. Patients were diagnosed as 7 boys and 37 girls, 30 right and 8 left as well as 6 bilateral, the age of the first dislocation was 2.64±1.54 years old and 4.52±2.64 years old at the age of diagnosis. The data of 39 patients took hip flexion, adduction, internal rotation or hip flexion and adduction as the mode of stimulating dislocation. There were 43 patients with posterior dislocation, 41 patients with an audible "click" sound during dislocation, 36 patients with painless dislocation, and 37 patients with "vacuum phenomenon" were captured at the moment of dislocation. All patients with HDH had no specific family history and obvious history of trauma. There was no significant difference in general data between observation and psychological intervention group, splint or brace fixation group as well as surgical treatment group ( P>0.05). Harris standard to evaluate hip function, CE angle and Reimers instability index of the affected side were significantly different from those before and after treatment at the moment of dislocation ( H=127.51, P<0.001; H=55.70, P<0.001; H=54.69, P<0.001). Compared with the immediate disappearance of dislocation in the surgical treatment group, the disappearance time of dislocation in the observation and psychological intervention group and the splint or brace fixation group were significantly longer, and the difference was statistically significant ( H=20.83, P<0.001). Conclusion:Without specific family history and obvious trauma at young girls, painless posterior dislocation of hip with an audible "click" sound and "vacuum phenomenon" at the moment of dislocation are the significant epidemiological characteristics of HDH. Observation and psychological intervention, splint or brace fixation are recommended as the initial treatment scheme. When conservative treatment is ineffective, surgical treatment is needed to stabilize the hip joint quickly.

The Responses of Light Reaction of Photosynthesis to Dynamic Sunflecks in a Typically Shade-Tolerant Species Panax notoginseng.

Light is highly heterogeneous in natural conditions, and plants need to evolve a series of strategies to acclimate the dynamic light since it is immobile. The present study aimed to elucidate the response of light reaction of photosynthesis to dynamic sunflecks in a shade-tolerant species Panax notoginseng and to examine the regulatory mechanisms involved in an adaptation to the simulated sunflecks. When P. notoginseng was exposed to the simulated sunflecks, non-photochemical quenching (NPQ) increased rapidly to the maximum value. Moreover, in response to the simulated sunflecks, there was a rapid increase in light-dependent heat dissipation quantum efficiency of photosystem II (PSII) (ΦNPQ), while the maximum quantum yield of PSII under light (F v'/F m') declined. The relatively high fluorescence and constitutive heat dissipation quantum efficiency of PSII (Φf,d) in the plants exposed to transient high light (400, 800, and 1,600 µmol m-2 s-1) was accompanied by the low effective photochemical quantum yield of PSII (ΦPSII) after the dark recovery for 15 min, whereas the plants exposed to transient low light (50 µmol m-2 s-1) has been shown to lead to significant elevation in ΦPSII after darkness recovery. Furthermore, PSII fluorescence and constitutive heat dissipation electron transfer rate (J f,d) was increased with the intensity of the simulated sunflecks, the residual absorbed energy used for the non-net carboxylative processes (J NC) was decreased when the response of electron transfer rate of NPQ pathway of PSII (J NPQ) to transient low light is restricted. In addition, the acceptor-side limitation of PSI [Y(NA)] was increased, while the donor-side limitation of photosystems I (PSI) [Y(ND)] was decreased at transient high light conditions accompanied with active cyclic electron flow (CEF). Meanwhile, when the leaves were exposed to transient high light, the xanthophyll cycle (V cycle) was activated and subsequently, the J NPQ began to increase. The de-epoxidation state [(Z + A)/(V + A + Z)] was strongly correlated with NPQ in response to the sunflecks. In the present study, a rapid engagement of lutein epoxide (Lx) after the low intensity of sunfleck together with the lower NPQ contributed to an elevation in the maximum photochemical quantum efficiency of PSII under the light. The analysis based on the correlation between the CEF and electron flow devoted to Ribulose-1, 5-bisphosphate (RuBP) oxygenation (J O) indicated that at a high light intensity of sunflecks, the electron flow largely devoted to RuBP oxygenation would contribute to the operation of the CEF. Overall, photorespiration plays an important role in regulating the CEF of the shade-tolerant species, such as P. notoginseng in response to transient high light, whereas active Lx cycle together with the decelerated NPQ may be an effective mechanism of elevating the maximum photochemical quantum efficiency of PSII under light exposure to transient low light.

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment / 中草药·英文版

Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Effects of source difference of sodium carboxymethyl starch on its properties and function / 药学学报

During the process of consistency evaluation, it was found that the consistency of drug release between generic and original brands in vitro was not sufficient to demonstrate their same release in vivo. The disintegration of tablets, as a premise for the release of tablet drugs, greatly affects the release of drugs, depending on the structure and properties of disintegrants. Hence the systematic research on disintegrants would be very important for the evaluation of generic consistency. In this experiment, the physicochemical properties and application of 11 different sodium carboxymethyl starch (CMS-Na) from 9 manufacturers were investigated. This provides the reference for selection of excipients for consistency evaluation. The particle morphology of CMS-Na was observed by scanning electron microscope. The particle size distribution was determined by dry particle size analyzer. The determination of pH and loss on drying was carried out according to the 2015 edition of Chinese pharmacopoeia method. The powder fluidity was evaluated with Carr's index, Hausner ratio and angle of repose. The disintegration performance of CMS-Na was evaluated through determining the water absorption and swelling. The disintegration effect of CMS-Na tablets was studied using lactose and microcrystalline cellulose as fillers. The results showed that pH values and weight loss on drying of all samples met the requirements, whereas the particle morphology, fluidity, water swell-ability and disintegration time had a large variation, which leads to the large differences the properties of CMS-Na depending on the sources. Therefore in order to ensure that the reproducibility of generic drugs from their name brand, our studies indicate that only a sizable choice of disintegrants could ensure good inter batch reproducibility.

Clinical observation of utilizing a transolecranon pin joystick technique in the treatment of multidirectionally unstable supracondylar humeral fractures in children / 中华骨科杂志

Objective:Compared with closed reduction and percutaneous pinning (CRPP) treatment, evaluating the clinical observation of utilizing a transolecranon pin joystick technique combined with CRPP in the teatment of multidirectionally unstable supracondylar humeral fractures in children.Methods:From thirty nine pediatric multidirectionally unstable supracondylar humeral fractures hospitalized between January 2012 and January 2019, twenty seven males (69.23%) and twelve females (30.77%) were included in the study, with a average age of 6.68±2.52 years (range, 2.17-13.75 y), twenty three fractures (65.7%) were treated with CRPP (CRPP group) and the remaining Sixteen fractures (41.03%) were treated utilizing a transolecranon pin joystick technique combined with CRPP (joystick group). Both groups were followed over 16 weeks. The paired sample t test or χ2 test and Fisher's exact test were used to compare the surgical time, times of fluoroscopy, quality of reduction and neurological or vascular complications, Baumann angle, carrying angle, lateralcapitellohumeral angle, postoperative range of motion as well as function-al outcomeduringthe Sixteen weeks and the last follow-up appointment. Results:All caseswere followed up for 1.98±1.43 years, and all fractures achieved clinical healing at 4 to 6 weeks postoperation. The surgical time and times of fluoroscopy were significantly shorter for patients in the joystick group (27.17±9.68 min, 24.25±5.92 times) when compared with CRPP group (48.59±15.75 min, 49.65±23.83 times, P<0.05). All cases showed restoration of the normal lateral capitellohumeral angle. Compared with Baumann angle of normal contralateral upper extremity during the sixteen weeks and the last follow-up appointment, the quality of reduction on the anteroposterior radiographic view was significantly better for patients in the joystick group than that of CRPP group ( P<0.05). The Baumann angle of the affected upper extremity was 77.70°±2.16°, and that of the normal contralateral upper extremity was 73.78°±4.04° in the CRPP group, joystick group was 73.06°±1.81° and 72.81°±3.45°, respectively at the sixteen weeks follow-up. The Baumann angle of the affected upper extremity was 77.13°±2.20°, and that of the normal contralateral upper extremity was 74.17°±4.17° in the CRPP group, joystick group was 72.69°±1.70° and 73.38°±3.48°, respectively at the last follow-up. The range of motion and clinical outcomes based on the criteria of Flynn were similar in both groups ( P<0.05). The elbow joint function of excellent and good rate of the criteria of Flynn was 82.61%, elbow flexion was 134.13°±8.61°, elbow extension was -3.48°±6.47° in the CRPP group, joystick group was 81.25%, 132.19°±9.48° and -3.44°± 4.37°, respectively at the sixteen weeks follow-up. The elbow joint function of excellent and good rate of the criteria of Flynn was 91.30%, elbow flexion was 140.14°±5.76°, elbow extension was -0.65±3.79° in the CRPP group, joystick group was 93.75%, 141.88°±5.12° and -0.31°±3.86°, respectivelyat the last follow-up. No immediate postoperative complications were observed. Conclusion:A transolecranon pin joystick technique combined with CRPP is a safe and effective method, can decrease surgical time and times of fluoroscopy and improve quality of reduction with no increasing risk of complications for closed reduction of multidirectionally unstable supracondylar humeral fractures in children.

Construction of a species-specific vector for improved plastid transformation efficiency in Capsicum annuum L.

In the present study, we focused on designing a species-specific chloroplast vector for Capsicum annuum L. and finding out its transformation efficiency compared to a heterologous vector. The plastid transformation vector (CaIA) was designed to target homologous regions trnA and trnI of IR region. A selectable marker gene aadA, whose expression is controlled by psbA promoter and terminator, was cloned between two flanking regions. A heterologous vector pRB95, which targets trnfM and trnG of LSC region along with aadA driven by rrn promoter and psbA terminator, was also used for developing plastid transformation in Capsicum. Cotyledonary explants were bombarded with stabilized biolistic parameters: 900 psi pressure and 9 cm flight distance, and optimized regeneration protocol (0.7 mg/L TDZ + 0.2 mg/L IAA) was used to obtain transplastomic lines on selection medium (300 mg/L spectinomycin). The aadA integration and homoplasmy were confirmed by obtaining 1.2 and 3.7 kb amplicons in CaIA transformants and subsequently verified by Southern blotting, whereas in pRB95 transformants, integration was confirmed by PCR with 1.45 kb and 255 bp amplicons corresponding to aadA integration and flanks, respectively. The transformation efficiencies attained with two plastid vectors were found to be 20%, i.e., 10 transplastomic lines in 50 bombarded plates, with CaIA and 2%, i.e., 1 transplastomic line in 50 bombarded plates, with heterologous pRB95, respectively.

Nanosecond shock wave-induced surface acoustic waves and dynamic fracture at fluid-solid boundaries.

We investigate the generation and propagation characteristics of leaky Rayleigh waves (LRWs) caused by a spherical shock wave incident on a water-glass boundary both experimentally and numerically. The maximum tensile stress produced on the solid boundary is attributed to the dynamic interaction between the LRWs and an evanescent wave generated concomitantly along the boundary. The resultant tensile stress field drives the initiation of crack formation from pre-existing surface flaws and their subsequent extension along a circular trajectory, confirmative with the direction of the principal stress on the boundary. We further demonstrate that this unique ringlike fracture pattern, prevalent in damage produced by high-speed impact, can be best described by the Tuler-Butcher criterion for dynamic failure in brittle materials. The orientation of the ring fracture extension into the solid also follows closely with the trajectory of the local maximum tensile stress distribution.

Exploration of novel pyrrolo[2,1-f][1,2,4]triazine derivatives with improved anticancer efficacy as dual inhibitors of c-Met/VEGFR-2.

c-Met and VEGFR-2 have attracted interest as novel targets for treatment of various cancers. Aiming to develop potent dual c-Met and VEGFR-2 inhibitors, a series of pyrrolo[1,2-f][1,2,4]triazine derivatives were designed and synthesized. The majority of target compounds exhibited potent antiproliferative effect against c-Met addictive cancer cell lines with IC50 values ranged from 1.2 to 24.6 nM, especially 27a. In-depth studies demonstrated 27a has great selectivity to c-Met and VEGFR-2, and potent inhibitory activity against them (IC50 of 2.3 ±â€¯0.1 nM and 5.0 ±â€¯0.5 nM). Furthermore, it also showed the highest anticancer activity with IC50 of 0.71 ±â€¯0.16 nM (better than the positive compound) against BaF3-TPR-Met and 37.4 ±â€¯0.311 nM (comparable to the positive compound) against HUVEC-VEGFR2, consistent with that in c-Met sensitive tumor cell lines. Subsequently, physicochemical and pharmacokinetic characterization indicated 27a has favorable druggability and pharmacokinetic properties. Further docking studies suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, also indicating that 27a was a potential candidate for cancer therapy deserving further study.

Application of colonoscopic tattooing with India ink for localization of colorectal lesions in laparoscopic surgery / 中国内镜杂志

Objective?To investigate the use of submucosal injection of India ink for localization of colorectal lesions in laparoscopic surgery, and to evaluate its efficiency and safety.?Methods?A retrospective study of 146 patients with colorectal lesions from January 2015 to November 2017, who underwent preoperative colonoscopic marking with India ink and subsequently received laparoscopic colectomy was conducted. 1.0 ml of physiologic saline solution was first injected into the submucosa to produce an artificial submucosal elevation, and then 0.2 ml of 1 : 10 diluted India ink followed with another 1ml of physiologic saline solution was injected. Operation time, success rate, complications, location efficiency, and postoperative pathology were evaluated.?Results?The India ink tattooing was easily applied for all patients without complication. At laparoscopic surgery, all lesions could be clearly visualized. No ink diffusion, leakage, and local inflammatory responses were observed. The surgical margins of all samples were tumor negative.?Conclusion?Preoperative submucosal tattooing with India ink is recommended as an easy, safe and economical procedure.

Expressions of CaSR and Claudin-14 and the formation of nanobacterial renal stone: A dynamic study / 医学研究生学报

Objective Nanobacteria are one of the factors for urinary calculi and its exact pathogenic mechanism is not yet clear.The aim of this study was to investigate the role of the CaSR -Claudin-14 regulatory channel in the formation of calculi . Methods Sixty Wistar male rats were equally randomized into a normal control group and nanobacterial group , the former injected via the tail vein with 1.2 mL of 0.9％ sodium chloride solution while the latter with 1.2 mL of nanobacterial suspension , both for once.Three of the rats in each group were sacrificed every week in the first 10 weeks after injection.Histopathological examination was performed every week to evaluate the stone formation in the kidneys of the rats , and the expressions of the CaSR and Claudin -14 proteins were determined by immunohistochemistry. Results From the 1st to the 10th week after injection, crystal particles were observed in the rat kidneys of the nanobacterial group, but not in the normal controls (52.4％ vs 0％, P<0.01).The expressions of CaSR and Claudin -14 showed no statistically significant differences between the nanobacterial and control groups in the first 3 weeks (P>0.05) but both gradually in-creased in the former group from the 4th to the 10th week as compared with the latter, mainly in membrane of the renal tubular epithelial cells. Conclusion The increased activity of the CaSR -Claudin-14 regulatory channel may play an important role in the formation of nanobacterial renal stone .

Reform and practice of biopharmaceutical experiment teaching / 中华医学教育探索杂志

Biological pharmaceutics is not only the important basic course in medicine,biotechnology,but also the course of combination of theory and practice.Experiment plays an important role in the teaching system of biological pharmaceutics.According to the characteristics of biopharmaceutical and the demand for talent cultivation,we have made some adjustments from the basic process of genetic engineering drug preparation such as rearranging biopharmaceutical experimental classes to form a systemic experiment content,increasing the experiment lesson,innovatively making the students participant in the experiment preparation,and opening the laboratory and improve the method of experiment examination.It has been proved that this teaching reform can improve the teaching quality of experimental class,and has valuable demonstration significance and reference value to the quality education and experimental teaching reform.

Clinical study of ultrasound - guided injection of platelet-rich plasma for the treatment of recalcitrant lateral epicondylitis / 介入放射学杂志

Objective To explore the clinical efficacy of ultrasound - guided injection of platelet-rich plasma (PRP) for the treatment of recalcitrant lateral epicondylitis. Methods From September 2014 to June 2016, a total of 15 patients with recalcitrant lateral epicondylitis received ultrasound - guided injection of autologous PRP therapy, including via left arm injection (n=2) and via right arm injection (n=13). By using twice centrifugal method, the patient' s own venous whole blood was centrifuged to obtain PRP. All patients underwent PRP injection once a week, a total of 3 treatments were performed for each patient. Results After the first injection of PRP, the patients were followed up for 12 months. One month after the treatment, visual analogue scale (VAS) score was obviously improved, at 3 months after the treatment the improvement of VAS score reached its peak and it remained at this level until 12 months after the treatment. The elbow joint function, which was evaluated with modified MAYO elbow score, was also significantly improved in one month after the treatment, and the clinical effect was sustained to 12 months after the treatment. Conclusion Ultrasound - guided precise injection of PRP can effectively improve the pain and the elbow joint function caused by recalcitrant lateral epicondylitis. (J Intervent Radiol, 2018, 27:238-241)

A haplotype in CFH family genes confers high risk of rare glomerular nephropathies.

Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster. The three variations, rs55807605, rs61737525 and rs57960694, have strong linkage disequilibrium; subsequent haplotype analysis indicated that ATA increased the susceptibility of these renal diseases. In silico analysis, the CFHR3 rs61737525-T risk allele altered the physical and structural properties and generated a reduction in binding affinity of the CFHR3/C3b complex. Surface plasmon resonance (SPR) binding analysis further demonstrated the substitution induced a decrease of two orders of magnitude in C3b-binding properties, with a declined cofactor activity in fluid phase. These data suggest that the haplotype carrying the causative allele behaves as a partial C3 convertase deficiency, predisposing individuals to diverse pathologic lesions underlying complement overactivation. Such genotype-phenotype discrepancies allow better understanding about these nephropathies mediated by genetic complement disorders.

Interaction between a bubble and a metal target for underwater laser propulsion.

Optical beam deflection and high-speed photographic methods are employed to investigate the interaction mechanism between a laser-induced bubble and a metal target for underwater laser propulsion. A preliminary theory is proposed to reveal the step increases of the kinetic energy transferred to the target during the process of increasing the incident laser energy. This theory also helps to explain the increasing coupling efficiency with incident laser energy for underwater laser propulsion.