Advances in physiological activities and synthesis of β-nicotinamide mononucleotide / 生物工程学报

Nicotinamide mononucleotide (NMN) is one of the key precursors of coenzyme Ⅰ (NAD+). NMN exists widely in a variety of organisms, and β isomer is its active form. Studies have shown that β-NMN plays a key role in a variety of physiological and metabolic processes. As a potential active substance in anti-aging and improving degenerative and metabolic diseases, the application value of β-NMN has been deeply explored, and it is imminent to achieve large-scale production. Biosynthesis has become the preferred method to synthesize β-NMN because of its high stereoselectivity, mild reaction conditions, and fewer by-products. This paper reviews the physiological activity, chemical synthesis as well as biosynthesis of β-NMN, highlighting the metabolic pathways involved in biosynthesis. This review aims to explore the potential of improving the production strategy of β-NMN by using synthetic biology and provide a theoretical basis for the research of metabolic pathways as well as efficient production of β-NMN.

A prospective study of the perforator evaluation and eccentric design of anterolateral thigh flap based on superficial fascial perforators assisted by modified computed tomography angiography / 中华烧伤杂志

Objective: To explore the preoperative whole perforator evaluation and intraoperative eccentric design of anterolateral thigh flap (ALTF) based on superficial fascial perforators by modified computed tomography angiography (CTA), and the clinical effects were observed. Methods: A prospective observational study was adopted. Twelve patients with oral and maxillofacial tumors and 10 patients with open injury of the upper limb with large soft tissue defects were hospitalized in the Department of Hand & Microsurgery and Department of Oral & Maxillofacial Surgery of Affiliated Hospital of Binzhou Medical University from January 2021 to July 2022, with 12 males and 10 females, aged from 33 to 75 years, an average age of 56.6 years. The wounds of the patients with oral and maxillofacial tumors were reconstructed by ALTF after the extensive tumor resection and radical cervical lymph node dissection in the same stage; the wounds of the patients with skin and soft tissue defect on the upper limb were covered by ALTF in stage Ⅱ after debridement in stage Ⅰ. After debridement, the area of wound was 3.5 cm×3.5 cm-25.0 cm×10.0 cm and the area of the required flap area was 4.0 cm×4.0 cm-23.0 cm×13.0 cm. Modified CTA scan was performed on the donor site of ALTF before the operation, with the parameters of modified CTA being set to mainly reduce the tube voltage and tube current, and increase the contrast dose and the dual phase scan. The acquired image data were sent to GE AW 4.7 workstation and adopted the volume reconstruction function for visual reconstruction and evaluation of the whole perforator. The information of perforator and source artery was marked on the body surface before operation according to the above evaluation. During the operation, an eccentric flap centered on the visible superficial fascia whole perforator was designed and cut according to the desired flap area and shape. The donor sites of the flap were repaired by direct sutures or full-thickness skin grafts. The total radiation dose was compared between the modified CTA scan and the traditional CTA scan. The distribution of outlet point of perforator of double thighs, the length and direction of superficial fascia perforators based modified CTA were recorded. The type, number, and origin of the target perforator, distribution of of outlet point of perforator, and the diameter, course, and branch of the source artery observed before the operation were compared with those observed during the operation. The healing of donor site wound and the survival of flaps in recipient site were observed after operation. The texture and appearance of flap, oral and upper limb functions, and the functions of femoral donor sites were followed up. Results: The total radiation dose of modified CTA scan was lower than that of the traditional CTA scan. A total of 48 perforators of double thighs were observed, among which, 31 (64.6%) perforators went outward and downward, 9 (18.8%) perforators went inward and downward, 6 (12.5%) perforators went outward and upward, and 2 (4.2%) perforators went inward and upward, and the average length of superficial fascia perforators was 19.94 mm. The preoperative observed type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery were basically consistent with the intraoperative exploration. The types of 15 septocutaneous (including musculoseptocutaneous) perforators and 10 musculocutaneous perforators observed before the operation was consistent with intraoperative exploration. The distance between the mark of the surface perforator point and the actual exit point of the perforator during operation was (0.38±0.11) mm. All flaps survived without vascular crisis. The donor site wounds of 5 cases of skin grafting and 17 cases of direct suturing wounds healed well. The postoperative follow-up was 2 months to 1 year, with an average of 8.2 months, the flaps were soft and slightly bloated; the function of diet and mouth closing was accessible in patients with oral and maxillofacial tumors, the speech function was mildly impaired in patients with tongue cancer, but they could complete basic oral communication; the wrist and elbow joints and forearm rotation function were not significantly limited in patients with upper limb soft tissue injuries; there was no obvious tightness in the donor sites, and the function of the hip and knee joints was not limited. Conclusions: The whole perforator and even the subcutaneous perforator of the donor site of ALTF can be evaluated by modified CTA, and the flap can be used in oral or maxillofacial reconstruction and repair of skin and soft tissue defects of upper limbs to achieve good results. By clarifying the type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery before the operation, the eccentric design of the ALTF based on the superficial fascia perforator was realized. This study has strong guiding value.

Endocrine aberrations of human nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic-pituitary-testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.

Advances on microbial synthesis of L-proline and trans-4-hydroxy-L-proline / 生物工程学报

L-proline (L-Pro) is the only imino acid among the 20 amino acids that constitute biological proteins, and its main hydroxylated product is trans-4-hydroxy-L-proline (T-4-Hyp). Both of them have unique biological activities and play important roles in biomedicine, food and beauty industry. With the in-depth exploration of the functions of L-Pro and T-4-Hyp, the demand for them is gradually increasing. Traditional methods of biological extraction and chemical synthesis are unable to meet the demand of "green, environmental protection and high efficiency". In recent years, synthetic biology has developed rapidly. Through the intensive analysis of the synthetic pathways of L-Pro and T-4-Hyp, microbial cell factories were constructed for large-scale production, which opened a new chapter for the green and efficient production of L-Pro and T-4-Hyp. This paper reviews the application and production methods of L-Pro and T-4-Hyp, the metabolic pathways for microbial synthesis of L-Pro and T-4-Hyp, and the engineering strategies and advances on microbial production of L-Pro and T-4-Hyp, aiming to provide a theoretical basis for the "green bio-manufacturing" of L-Pro and T-4-Hyp and promote their industrial production.

Epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female (P=0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z=1.769, P=0.049), and the strongest correlation in 2016 (Moran's I=0.328, Z=4.979, P=0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.

Research progress of exosomes in the treatment of retinal ischemia-reperfusion injury / 中华眼底病杂志

Exosomes are nanovesicles actively secreted by cells, which selectively encapsulate biologically active molecules such as proteins, RNA, and cytokines. They play an important role in intercellular communication, immune regulation, and maintenance of homeostasis, which can also be used as carriers for targeted drug delivery. Retinal ischemia-reperfusion injury (RIRI) is a retinopathy that seriously threatens human vision. At present, the clinical treatment of these diseases are symptomatic treatments, and some patients have poor efficacy or even blindness. As extracellular vesicles rich in functional proteins and RNAs, exosomes can not only be used as drugs for the treatment of RIRI, but also be used as carriers for drug delivery to play synergistic therapeutic effects. In the future, with the deepening of the research on the molecular structure, contents and biological functions of exosomes, as well as the continuous development of ophthalmic biology and genetic engineering technology, exosomes are expected to exert their great potential as therapeutic drugs and carriers, and become an important means of treating RIRI.

Correlative analysis of cervical curvature and atlantoaxial instability / 中国骨伤

OBJECTIVE@#To investigate the correlation between the changes of cervical curvature and atlantoaxial instability.@*METHODS@#The correlation between the changes of cervical curvature and atlantoaxial instability was retrospectively studied in 50 outpatients with abnormal cervical curvature (abnormal cervical curvature group) from January 2018 to December 2019. There were 24 males and 26 females in abnormal cervical curvature group, aged from 18 to 42 years old with an average of(30.62±5.83) years. And 53 patients with normal cervical curvature (normal cervical curvature group) during the same period were matched, including 23 males and 30 females, aged from 21 to 44 years with an average of(31.98±6.11) years. Cervical spine X-ray films of 103 patients were taken in lateral position and open mouth position. Cervical curvature and variance of bilateral lateral atlanto-dental space(VBLADS) were measured and recorded, Pearson correlation coefficient analysis was used to study the correlation between the changes of cervical curvature and atlantoaxial instability.@*RESULTS@#Atlantoaxial joint instability accounted for 39.6%(21/53) in normal cervical curvature group and 84.0%(42/50) in abnormal cervical curvature group. There was significant difference between two groups(P<0.01). VBLADS in abnormal cervical curvature group was (1.79±1.01) mm, which was significantly higher than that in normal cervical curvature group(0.55±0.75) mm(P<0.01). Pearson correlation coefficient analysis showed that the size of cervical curvature was negatively correlated with VBLADS.@*CONCLUSION@#Cervical curvature straightening and inverse arch are the cause of atlantoaxial instability, the smaller the cervical curvature, the more serious the atlantoaxial instability.

Effect of acupuncture on serum PYY and nesfatin-1 in obese patients with insulin resistance / 针灸推拿医学（英文版）

Objective: To observe the effect of acupuncture on serum peptide YY (PYY) and nesfatin-1 in obese patients with insulin resistance. Methods: Ninety-eight obese patients with insulin resistance were divided into a control group and an observation group by the random number table method, with 49 cases in each group. The control group received exercise and dietary interventions, and the observation group received additional acupuncture treatment to the exercise and dietary interventions. The body mass index (BMI), body fat percentage, fasting insulin (FINS), fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), and serum PYY and nesfatin-1 levels were compared before and after treatment. The efficacy was evaluated after treatment. Results: The total effective rate was significantly higher in the observation group than in the control group (P<0.05). After treatment, the BMI, body fat percentage, and serum TG and TC levels decreased significantly in both groups (P<0.05), and were significantly lower in the observation group than those in the control group (P<0.05). The FINS, FPG, HOMA-IR, and serum PYY and nesfatin-1 levels of the control group were not significantly changed after treatment (P>0.05). The FINS, FPG and HOMA-IR of the observation group decreased significantly after treatment (P<0.05), and were lower than those in the control group (P<0.05). The serum PYY and nesfatin-1 levels of the observation group increased significantly after treatment (P<0.05), and were higher than those in the control group (P<0.05). Conclusion: Based on exercise and dietary interventions, acupuncture is effective for obese patients with insulin resistance. It can reduce the BMI, body fat percentage, blood lipids, blood glucose, and serum insulin levels and improve insulin resistance. The action may be associated with the up-regulation of serum PYY and nesfatin-1.

Clinical significance of suction blister transplantation in improving efficacy of ReCell technique in treatment of vitiligo / 中华医学美学美容杂志

Objective:To investigate the clinical significance of suction blister transplantation in improving the efficacy of ReCell technique in the treatment of vitiligo.Methods:Patients were divided into three groups, namely, vitiligo patients without history of suction blister therapy, patients with ineffective suction blister therapy and patients with effective suction blister therapy. There were 30 patients in each group. All patients were treated with standard procedure of ReCell technique. The color recovery effect of leukoplakia was observed 3 and 6 months after operation, and the incidence of complications was also observed.Results:The effective rate of color recovery 3 and 6 months after operation were as follow: in patients without history of suction blister group, the effective rate of three months was 53.3%, and that of six months was 63.3%; in patients with ineffective suction blister group, the effective rate was 43.3% in three months and 50.0% in six months, and in patients with effective suction blister group, the effective rate was 76.7% in three months and 90.0% in six months. No obvious complications were observed in the three groups.Conclusions:For the treatment of stable vitiligo with ReCell technique, suction blister method is a simple and effective method for screening patients.

Difference of clinical characteristics in ocular toxocariasis between adults and children and characteristics of anti-toxocaria antibody in intraocular fluids / 中华眼底病杂志

Objective:To compare the clinical manifestations of ocular toxoplasmosis (OT) in adult and children, and to preliminarily explore the role of intraocular fluid detection in the early diagnosis of OT.Methods:A retrospective study. From January 2018 to October 2019, 60 cases of OT patients with 60 eyes diagnosed in the Department of Ophthalmology of Beijing Chaoyang Hospital Affiliated of Capital Medical University were included in the study. The medical history information of patients was collected in parallel with slit-lamp microscopy, indirect ophthalmoscope examination, and canine toxoplasma antibody detection in aqueous or vitreous fluid. Fifty-eight cases underwent visual inspection; 2 cases did not underwent visual inspection, who were children. The visual acuity examination was carried out using the new version of the standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution(logMAR) visual acuity during statistics. According to age, the patients were divided into adult group and child group, with 12 eyes in 12 cases and 48 eyes in 48 cases, respectively. The clinical characteristics and main points of diagnosis and treatment of the two groups of patients were compared and observed. The comparison among the measurement data groups conforming and the normal distribution was performed by the independent t test. The comparison between the measurement data groups of the skewed distribution was performed by the Kruskal- Wallis test. The qualitative data were compared with χ 2 test. Results:Among the adult group and the child group, 7 (58.3%, 7/12) and 34 (70.8%, 34/48) patients with a clear history of contact with dogs and cats were in the adult group and the child group, respectively. The adult group was significantly lower than the child group, however, there was no different statistical significance ( χ 2=0.236, P=0.627). At the first visit, the self-reported blurred vision of the adult group and the child group was 10 (83.3%, 10/12) and 22 (45.8%, 22/48) cases, respectively. In the adult group and the child group, 3 (25.0%, 3/12) and 20 (43.5%, 20/46) eyes with logMAR visual acuity greater than 1.85, 8 (66.7%, 8/12) and 22 (45.8%, 22/46) eyes with logMAR visual acuity less than 0.3. The visual acuity of the adult group was better than that of the child group, and the difference was statistically significant ( Z=2.162, P=0.031). There was no statistically significant difference in the composition ratio of different clinical types of the two groups of eyes ( χ 2=1.908, P=0.385). The incidence of inflammation in the anterior segment of the eye in the adult group and the child group were 25.0% (3/12) and 56.3% (27/48), respectively; there was no statistically significant difference between the two groups ( χ 2=3.750, P=0.053). The concentration of antibodies in the vitreous humor of the affected eye in the adult group and the child group was greater than that of aqueous humor. The antibody concentrations of vitreous humor and aqueous humor were 36.51 (22.58) and 19.94 (21.78) U/ml in the children group; 45.95 (56.44) and 32.20 (38.64) U/ml in the adult group. Comparison of antibody concentrations in the vitreous humor and aqueous humor of the affected eyes in the child group showed statistically significant differences ( Z=-1.984, P=0.047). Conclusions:Compared with children with OT, adult patients with OT have better vision and mild inflammation or hyperplasia of the vitreous cavity. The detection of antibodies related to toxoplasma in the intraocular fluid is helpful for early diagnosis.

Proper use of examination of intraocular fluid to assist precise diagnosis and treatment of vitreoretinal diseases / 中华眼底病杂志

There are many types of fundus diseases and their causes are complex. They can be caused by metabolic factors or inflammatory factors. Fundus examination and imaging examination tools are the main methods for diagnosing fundus diseases. However, in terms of determining the cause and early diagnosis, if the intraocular fluid detection technology can be reasonably combined, the advantages will be greater. Intraocular fluid is the general term for fluid in the eyeball, including aqueous humor, vitreous humor, etc. The molecular components that can be tested include DNA, RNA, antigens, antibodies, and cytokines. With the advancement of molecular testing technology and equipment, intraocular fluid testing as an evidence-based method has gradually been incorporated into the consensus and guidelines of more fundus disease experts, and is mainly used for infectious fundus diseases and camouflage syndromes. Reasonable use of intraocular fluid testing can help improve the personalized diagnosis and treatment of fundus diseases and reduce unnecessary drug overuse. However, it is worth noting that intraocular fluid detection is only one of many tools and cannot replace other examinations and clinical experience. Excessive intraocular fluid testing not only increases the risk of clinical infections because of invasiveness, but also increases the burden on patients.

Efficacy of remimazolam combined with low-dose propofol for sedation during induction of anesthesia / 中华麻醉学杂志

Objective:To evaluate the efficacy of remimazolam combined with low-dose propofol for sedation during induction of anesthesia.Methods:A total of 228 patients of both sexes, aged 18-64 yr, with body mass index of 19-35 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic cholecystectomy, were divided into 2 groups ( n=114 each) by a random number table method: remimazolam combined with low-dose propofol group (group R) and propofol group (group P). Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, remimazolam 0.3 mg/kg, propofol 0.5 mg/kg and micuronium 0.2 mg/kg in group R, and sufentanil 0.3 μg/kg, propofol 2 mg/kg and micuronium 0.2 mg/kg in group P. Endotracheal intubation was performed when bispectral index value ≤ 50.Before induction (T 0), immediately before intubation (T 1), at 1 min (T 2) and 3 min (T 3) after intubation, mean arterial pressure (MAP) and heart rate (HR) were recorded.The anesthesia induction time and the incidence of hypotension and bradycardia were recorded in the two groups. Results:There was no significant difference in MAP and HR at T 0 between the two groups ( P>0.05). Compared with the value at T 0, MAP in two groups and HR were significantly decreased at T 1-3 in group P ( P<0.01). Compared with group P, the anesthesia induction time was significantly prolonged, and hypotension and bradycardia was decreased in group R ( P<0.05). Conclusion:The combination of remimazolam and low-dose propofol exerts better efficacy for sedation during induction of anesthesia than propofol alone.

Application progress of flow cytometry in the cytokine test and cytological examination for ocular diseases / 中华实验眼科杂志

As an advanced quantitative technology for cells, flow cytometry, which can make multi-paramter quantitative analysis and sorting of individual cells or biological particles, has been widely used in immunology, oncology, hematology and other fields of medical research and clinical diagnosis in recent years.It can quantitatively detect the expression levels of cytokines and the distribution characteristics of cell subsets in the intraocular fluid.Compared with traditional enzyme-linked immunosorbent assay, cell morphology and immunohistochemistry, it has the advantages of simple operation, smaller sample size, higher sensitivity and higher throughput.Flow cytometry has been widely used in the detection and subgroup analysis of cytokines related to eye diseases, such as intraocular angiogenesis, intraocular lymphoma, retinopathy, cataract, uveitis, sarcoidotic uveitis, infectious intraocular inflammation, etc.Flow cytometry plays an increasingly important role in the pathogenesis research and targeted therapy of eye diseases.In this article, the application of flow cytometry in the examination of cytokines and cytology in ocular fluid for ocular diseases were reviewed.

Review on the detection of tear pathogen and immune component and its clinical significance / 中华实验眼科杂志

Ocular surface diseases are common diseases in ophthalmology.It is difficult for clinicians to make early and accurate diagnosis based on symptoms, signs and serologic examination.Compared with the blood test, the tear test can reflect the condition of the local ocular surface and it has the characteristics of being non-invasive, having high diagnostic accuracy and fast diagnostic speed.Tear detection uses modern detection techniques such as polymerase chain reaction, enzyme-linked immunosorbent assay, gene chip and protein chip to detect the pathogen and immune components in tear, including microbial nucleic acid, tear antibody (IgM, IgG, IgE, IgA, antinuclear antibody, etc.) and cytokines (interleukin, tumor necrosis factor, interference factor, transforming growth factor, epidermal growth factor, etc.). Tear detection provides information about the pathogen infection and immune response on the ocular surface.At present, a large number of domestic and foreign tear detection studies show that there are certain regular changes in tear composition, not only in ocular surface diseases, uveitis, fundus diseases, thyroid related ophthalmopathy, but even in systemic diseases such as diabetes, hepatitis B, acquired immune deficiency syndrome etc.In addition, the research of tear pathogen and immune components is of great significance to study the cause, biochemical and immune process, treatment of diseases.In this paper, the latest research progress of tear collection, the clinical significance of tear pathogen and immune components and the characteristics of tear in various diseases was summarized and analyzed to provide reference for clinical practice.

A comparative study of vancomycin loaded bone cement in the treatment of Wagner Ⅱ-Ⅳ diabetic foot / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of vancomycin bone cement in the treatment of diabetic foot ulcer (DFU) ruptured Wagner gradeⅡ-Ⅳ.@*METHODS@#From March 2019 to April 2021, 32 patients with Wagner gradeⅡ-Ⅳ diabetic foot were divided into vacuum sealing drainage (VSD) group and bone cement group according to different treatment methods. There were 16 cases in VSD group, 8 males and 8 females;the age ranged from 66 to 81 (70.50±7.20) years, and the course of disease ranged from 8 to 40 (27.56±8.55) months;Wagner gradeⅡin 2 cases, grade Ⅲin 7 cases and grade Ⅳin 7 cases;debridement and VSD were used. There were 16 cases in the bone cement group, 9 males and 7 females;the age ranged from 63 to 79 (69.56±7.29) years, and the course of disease ranged from 11 to 39(22.75±11.43) months;Wagner gradeⅡ in 2 cases, grade Ⅲin 5 cases and grade Ⅳ in 9 cases;vancomycin loaded bone cement was used for treatment. The types of bacteria, negative time of bacterial culture, skin healing time, hospital stay, operation times and complications were observed and compared between two groups.@*RESULTS@#All patients were followed up for 3 to 6 (4.00±1.07) months. The bacterial negative time, skin healing time and hospital stay in bone cement group were significantly lower than those in VSD group (@*CONCLUSION@#Vancomycin loaded bone cement is effective in the treatment of Wagner grade Ⅱ-Ⅳ diabetic foot ulceration wounds. It can reduce the length of hospital stay, shorten the healing time of skin and kill pathogens as soon as possible. It is one of the effective methods to treat Wagner gradeⅡ-Ⅳdiabetic foot ulceration.

Immune characteristics of Plasmodium reinfections in mice following chloroquine cure of primary Plasmodium infections / 中国血吸虫病防治杂志

ObjectiveTo investigate the disease progression and immunoprotective characteristics in mice re-infected with homogeneous/heterogeneous Plasmodium strains following cure of Plasmodium infections with chloroquine at the peak of parasitemia. MethodsC57BL/6 mice were infected with the non-lethal P. yoelii 17XNL strain, and half of mice were given treatment with chloroquine at the peak of parasitemia (9 days post-infection), while the other mice were self-cured naturally. Then, all cured mice were re-infected with the equivalent lethal P. yoelii 17XL or P. berghei ANKA strain 90 days following primary Plasmodium infections. The parasitemia levels during primary infections and reinfections were measured by microscopic examinations of Giemsa-stained thin blood films, and the levels of the IgG antibody in sera and the percentages of memory T cell subsets in spleen cells were detected in mice using ELISA and flow cytometry before and after parasite reinfections, respectively. Results Following primary infections with the P. yoelii 17XNL strain, the serum IgG antibody levels were (5.047 ± 0.924) pg/mL in the selfcured mice and (4.429 ± 0.624) pg/mL in the chloroquine-treated mice, respectively (t = 0.437, P > 0.05), which were both significantly higher than that in the uninfected mice (1.624 pg/mL ± 0.280 pg/mL) (F = 22.522, P < 0.01). There was no significant difference in the serum IgG antibody level among self-cured and chloroquine-treated mice re-infected with the P. yoelii 17XL strain or the P. berghei ANKA strain (F = 0.542, P > 0.05); however, the serum IgG antibody levels were all significantly higher in selfcured and chloroquine-treated mice re-infected with the P. yoelii 17XLstrain[(15.487±1.173)pg/mLand(15.965±1.150)pg/mL] or the P. berghei ANKA strain [(14.644 ± 1.523) pg/mL and (15.185 ± 1.333) pg/mL] relative to primary infections (F = 67.383, P < 0.01). There was no significant difference in the proportion of CD4+ [(34.208 ± 2.106), (32.820 ± 1.930), (34.023 ± 2.289), (35.608 ± 1.779) pg/mL] or CD8+ T memory cells [(17.935 ± 2.092), (18.918 ± 2.823), (17.103 ± 1.627), (17.873 ± 1.425) pg/mL] in self-cured and chloroquine-treated mice with primary infections with the P. yoelii 17XNL strain followed by re-infections with the P. yoelii 17XL strain or the P. berghei ANKA strain (F = 0.944 and 0.390, both P > 0.05); however, the proportions of the CD4+ or CD8+ T memory cells were significantly greater in self-cured and chloroquine-treated mice with primary infections with the P. yoelii 17XNL strain followed by re-infections with the P. yoelii 17XL strain or the P. berghei ANKA strain than in mice with primary infections (F = 50.532 and 21.751, both P < 0.01). Conclusions The cure of murine Plasmodium infections with chloroquine does not affect the production of effective immune protections in mice during parasite re-infections. Following a primary infection, mice show a protection against re-infections with either homogeneous or heterogeneous Plasmodium strains, and a higher-level resistance to re-infections with homogeneous parasite strains is found than with heterogeneous strains.

Anatomical study on the feasibility of a new self-guided pedicle tap / 中国骨伤

OBJECTIVE@#To evaluate the accuracy and safety of pedicle screw placement using a new self-guided pedicle tap.@*METHODS@#According to the anatomical characteristics of the pedicle, a new self-guided pedicle tap was developed. Six adult spinal specimens including 4 males and 2 females were selected and tapped thread on the right and left sides of each pair of pedicles from the same segment T to L with traditional taps (control group) and new self-guided pedicle taps (experimental group), respectively. And the pedicle screws were placed. The screwing time was recorded and compared between two groups. CT scanning was completed to observe the accuracy and safety of the screw placement according to the Heary classification of imaging results.@*RESULTS@#The screwing time of thoracic and lumbar vertebrae in the experimental group were (5.87±1.25) min and(5.45±1.67) min, respectively. While those in the control group were (6.12±1.69) min and (6.22±2.13) min, respectively. Then there was no significant difference in screwing time of thoracic and lumbar vertebrae between two groups (>0.05). The Heary grade of the pedicle screw showed that Heary gradeⅠand Heary gradeⅠ+Ⅱwere respectively 86 (84.31%) and 96 (94.12%) in the experimental group, 72 (71.29%) and 84 (83.17%) in control group, and the difference between two groups was statistically significant (<0.05).@*CONCLUSION@#The new self-guided pedicle tap can accurately and safely insert the thoracolumbar pedicle screw, with low cost, easy operation, and good clinical application value.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study / 中华医学杂志(英文版)

BACKGROUND@#Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.@*METHODS@#We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.@*RESULTS@#At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.@*CONCLUSIONS@#The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.@*TRIAL REGISTRATION@#ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the mechanism of modified Guipitang in the treatment of Yin-Fire insomnia with anxiety with the help of network pharmacological analysis technology. Method:Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the main components and target genes of modified Guipitang. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to establish the target gene sets of insomnia and anxiety. STRING 11.0 software was used to analyze the interaction between the overlapping genes, and Cytoscape_3.6.1 software analysis and Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Based on the results of network analysis, 48 SD female rats were randomly divided into blank control group, model group, eszopiclone tablets group (0.2 mg·kg-1·d-1), modified Guipitang low，medium，and high-dose groups (0.31，1.25，5 g·kg-1·d-1). The model of insomnia with anxiety was established by intraperitoneal injection of Para-chlorophenylalanine (PCPA) and these rats were treated with corresponding drugs for 7 days. Then the frequency, time and distance of the activities were observed in the experiment of autonomic activity. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expressions of proactivated protein kinase 8 (MAPK8), RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 3 (MAPK3) and interleukin-6 (IL-6) in rat hippocampus. Result:A total of 228 active compounds were screened from TCMSP database and 181 intersecting genes of diseases and drugs were obtained by comparing with GeneCards and OMIM comprehensive database. 9 core genes, including MAPK3, MAPK8, Akt1 and IL-6 were identified by STRING software and MCC algorithm. Animal experiments showed that the number of activity times, time and distance of modified Guipitang in high and medium dose groups were significantly lower than those in the model group. The high and middle dose groups of modified Guipitang could significantly inhibit the mRNA expression of MAPK3, MAPK8, Akt1 and IL-6 in hippocampus（P<0.01）, while the low dose group had no significant effect. Conclusion:The mechanism of modified Guipitang in treating Yin-fire insomnia with anxiety may be related to the regulation of MAPK3, MAPK8, Akt1 and IL-6 genes.