Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

Objective To establish an analytical method based on ultra-high performance liquid chromatogra-phy-tandem mass spectrometry(UPLC-MS/MS)technology for simultaneous detection of serum folate and its metab-olites 5-methyltetrahydrofolate,formyl tetrahydrofolate,and methotrexate concentration.Methods Target an-alytes in samples were concentrated and enriched using solid-phase extraction,separated by an Acquity UPLC HSS T3 chromatographic column(2.1 mm×100 mm,1.8 μm),and eluted with a gradient using 0.1％formic acid water and acetonitrile as the mobile phase.The method was established using an ultra-high performance liquid chromatography-tandem quadrupole mass spectrometer(UPLC I-Class Xevo TQ-S micro IVD)and ac-cording to CLSI C62-A and other documents,the performance of this method in terms of quantification limit,linear range,precision,accuracy,dilution effect,carrying contamination,specificity,interference testing and so on was evaluated.Results The quantitation limit for folate was 1 ng/mL,and the quantitation limits for 5-methyltetrahydrofolate,formyltetrahydrofolate,and methotrexate were 5 ng/mL.Folate had a good linear re-lationship in the concentration range of 1-200 ng/mL(R2＞0.99),and 5-methyltetrahydrofolate,formyltet-rahydrofolate,and methotrexate had linear ranges of 5-2 000 ng/mL(R2＞0.99).The intra-day precision ranged from 1.7％to 13.9％,and the inter-day precision ranged from 2.7％to 14.6％.The spiked sample re-covery rates ranged from 93.6％to 108.9％,showing good precision and accuracy.Other examination results,such as dilution effect,carryover,and specificity,met evaluation requirements.Conclusion This study estab-lished an accurate and efficient UPLC-MS/MS method that allows for the simultaneous detection of serum fo-late and its metabolites and methotrexate blood concentrations.This method not only aids clinicians in simul-taneously monitoring methotrexate blood concentration and calcium formyl tetrahydrofolate concentration,but also enables dynamic observation of changes in total folate and active folate levels in patients during the treat-ment process.It lays the foundation for developing a reasonable rescue plan for calcium folinate and further improving the safety and effectiveness of methotrexate treatment.

The five core indicators(the case mix index, the proportion of level-4 surgery, the proportion of technical service income in medical income, the proportion of personnel expenditure in business expenditure, and the proportion of fixed part in personnel salary) and target values determined by the pilot goal of high-quality development of high-level public hospitals jointly built by National Health Commission and Provincial Government had become the core indicators for evaluating the quality and efficiency of public hospital development. The authors proposed the optimization and improvement measures for the five core indicators one by one from the internal reform and innovation in hospitals, as well as the synergetic development and governance of " insurance-medical-medicine linkage", combined with the current situation of a pilot hospital. The authors also proposed the starting points and driving force for promoting the high-quality development of public hospitals through the synergetic development and governance of " insurance-medical-medicine linkage", including implementing government investment responsibilities, streamlining the price evaluation of medical services, deepening the reform of medical insurance payment, accelerating the expansion of drug and consumable procurement, and promoting the application of advanced technologies and products, in order to provide reference for the in-depth promotion of high-quality development of public hospitals.

Objective:To analyze the internal conditions and external environment of high-quality development of high-level public hospitals and establish a high-quality development strategy model, for reference of public hospitals to formulate and implement high-quality development strategies.Methods:The case hospital was a pilot in high-quality development of high-level public hospitals. SWOT method was used to analyze the influencing factors, AHP analytic hierarchy process was used to compare the importance of each influencing factor, and then the four-quadrant coordinate system method was used to establish a high-quality development strategy model.Results:The total strength(S), the total weaknesses(W), the total opportunity(O), and the total threat(T)were 0.095, 0.063, 0.065 and 0.024 respectively, reflecting that the strength of internal conditions was greater than the weaknesses, and the opportunities of external environment were greater than the threats. In the four-quadrants, the growth strategy model had the largest triangle area(0.003), and the strategic quadrilateral center of gravity was located in the opportunity area of the growth strategy.Conclusions:High-level public hospitals as represented by the case hospital had entered a period of important strategic opportunities, which the external opportunities were greater than its own strength. These hospitals were recommended to fully leverage the external opportunities, adopt a positive growth oriented(SO)strategy, formulate a development strategy with their own characteristics, promote the interaction of internal conditions and external environment to form new momentum, hence achieving high-quality development.

Objective:To develop an evaluation index system for the management ability of general practice team leaders in community health service centers.Methods:Based on literature review, key insider interviews and other methods, the framework and indicator pool for management capability of general practice team leaders were formed. Two rounds of Delphi consultations with 15 experts were conducted from July to October 2021, and the evaluation index system of general practice team leaders' management ability established.Results:All 15 experts had at least 5 years of work experience, including 10 engaging in clinical general practice, 3 in public health and 2 in community management. The response rates for the two rounds of expert consultation was 15/15, and the expert authority coefficient was 0.84, with Kendall's W coefficient of 0.35 ( P<0.001) and 0.46 ( P<0.001), respectively. Finally, the evaluation index system of the management ability of general practice team leaders was established, which consisted of 5 primary indicators (personal quality, special business management, organizational management, teaching and research management, strategy and culture building), 11 secondary indicators and 37 tertiary indicators. Conclusions:The management capability evaluation index system general practitioner team leaders of the community health centers has been established in this stu, which may be used for the training and selection of general practice team leaders in the community health centers.

Objective:To investigate the effects of anxiety and depressive symptoms in mediation of pain catastrophizing on disability in patients with low back pain.Methods:A cross-sectional survey was conducted among 97 patients with low back pain in the Changjiang Subdistrict community health center from July to October 2021. Oswestry Disability Index, pain catastrophic subscale in Coping Strategies Questionnaire-24, Generalized Anxiety Disorder Scale-short version, Patient Health Depression Questionnaire-short version were used to evaluate the activity dysfunction, pain catastrophic cognition and anxiety and depression levels of patients,respectively. Path analysis was implemented to test the mediation model, and the indirect effects were assessed using the bootstrap procedure with bias-corrected 95 %CI. Results:Results suggested significant positive correlations among pain catastrophizing, anxiety, depressive symptoms and disability of patients. In addition, both anxiety and depressive symptoms significantly mediated the impact of pain catastrophizing on disability (standardized indirect effects were 0.183 and 0.197, P<0.05). Patients with higher levels of pain catastrophic cognition showed higher levels of anxiety and depressive symptoms (β=0.757, 0.720; P<0.01), and reported more severe motor dysfunction (β=0.241, 0.274; P<0.05). Conclusions:Our findings suggest that anxiety and depression may be the psychological pathways through which pain catastrophizing predicts disability in patients with low back pain. Effective psychological interventions, such as emotion regulation and stress reduction strategies should be considered in treatment and supportive care for patients with low back pain.

Microcystis aeruginosa, a type of algal bloom microalgae, is widely distributed in water, causing serious deteriorated effects on humans and the ecological environment. As a biocontrol microorganism, Bacillus subtilis can synthesize various bioactive substances through non-ribosomal peptide synthetase, to inhibit the growth of M. aeruginosa. Thus, it is imperative to investigate the non-ribosomal peptide (NRP) metabolites of B. subtilis fmb60. Three NRP metabolites from B. subtilis fmb60 including bacillibactin, surfactin and fengycin were extracted and identified by genome mining technology. The growth inhibition of M. aeruginosa was studied by adding various concentrations of NRP metabolites. The half-effect concentration value (EC50.4 d) of M. aeruginosa was 26.5 mg/L after incubation for 4 days. With the increasing concentration, the inhibitory effects of NRP metabolites of B. subtilis fmb60 on M. aeruginosa was enhanced significantly. Compared with the control group, with the addition of 50 mg/L NRP metabolites to the M. aeruginosa, the content of Fv/Fm, Fv/Fo and Yield parameter after cultured for 4 days were decreased by 2.8%, 1.7% and 2.0%, respectively. Those findings indicate that the NRP metabolites of B. subtilis fmb60 can significantly inhibit the photosynthesis and metabolism of M. aeruginosa, which provides a theoretical foundation for the development of biological algae inhibitor of B. subtilis.
Bacillus subtilis ; Humans ; Microcystis ; Peptides ; Photosynthesis

Objective:To investigate the effect of volar plate internal fixation with modified Henry approach with pronator quadratus preservation for distal radius fractures in elderly patients.Methods:A retrospective case control analysis was performed on 78 elderly patients with distal radius fractures treated with volar plate internal fixation from February 2016 to December 2018 in Second Affiliated Hospital of Wenzhou Medical University and People's Hospital of Qingtian. There were 36 males and 42 females, aged 60-79 years [(66.5±5.6)years]. According to AO classification, there were 16 patients with type B1 fractures, 15 with type B2, 11 with type B3, 12 with type C1, 14 with type C2 and 10 with type C3. Of all, 40 patients were operated using modified Henry approach with pronator quadratus preservation (improvement group) and 38 using Henry approach with pronator quadratus cutting (traditional group). All patients were treated with volar plate internal fixation. The fracture healing, internal fixation and complications were observed. The wrist pain visual analogue score (VAS), forearm rotation range and grip strength were compared between the two groups at 1 week, 1 month, 3 months and 12 months postoperatively. The wrist joint function score of the two groups was compared by using the upper limb function assessment table (DASH) at 3 months and 12 months postoperatively.Results:All patients were followed up for 12-24 months [(15.2±6.3)months]. All fractures were healed after 3 months. The position of internal fixation was good, and there were no complications of infection, nonunion, plate loosening and tendon injury. During the follow-up period, 2 patients in traditional group had carpal tunnel syndrome, which was relieved after removal of internal fixation. The VAS in improvement group was lower than that in traditional group at 1 week, 1 month and 3 months postoperatively [(6.17±0.40)points vs. (6.80±0.45)points, (5.54±0.40)points vs. (6.08±0.70)points, (3.18±0.30)points vs. (3.75±0.40)points, respectively] ( P<0.05). The forearm rotation range in improvement group was larger than that in traditional group at 1 week, 1 month and 3 months postoperatively [(49.40±17.5)% vs. (40.3±13.2)%, (66.7±14.3)% vs. (54.2±18.7)%, (87.3±7.2)% vs. (80.7±8.1)%, respectively] ( P<0.05). There was no significant difference in VAS and forearm rotation range between the two groups at 12 months postoperatively ( P>0.05). There was no significant difference in grip strength between the two groups at 1 week, 1 month, 3 months and 12 months postoperatively ( P>0.05). There was no significant difference in DASH score between the two groups at 3 months and 12 months postoperatively ( P>0.05). Conclusion:For elderly patients with distal radius fracture, modified Henry approach with pronator quadratus preservation combined with volar plates is relatively better in alleviating postoperative pain, improving early rotation function and promoting early functional recovery.

Objective This paper focuses on the field of clinical medicine,with the aim of verifying the feasibility of interdisciplinary literature evaluation model based on feature matching method,to provide support for further interdisciplinary scientific research evaluation.Methods Feature matching method,Delphi expert enquiry,and normalization method were adopted to establish an evaluation system in clinical medicine,which was further verified by case studies.Results The normalization coefficient reflects the difficulty of publishing articles with high impact factors.Through the process of feature matching and normalization,it was found that compared with the fields of Neurology,Psychiatry and Surgery,researchers in the fields of Oncology and Internal Medicine were more likely to publish articles with high impact factors.Conclusions Through case analysis,this study verifies the feasibility of interdisciplinary scientific paper evaluation system.The interdisciplinary paper evaluation system based on feature matching method and normalized evaluation method comprehensively considers the characteristics of various disciplines of clinical medicine and provides a new idea for the evaluation of clinical scientific research talents.

Objective To establish a BALB/c mouse model of total hysterectomy and to investigate and analyze its characteristics and formation mechanism. Methods The control group was fed conventionally without any treatment. The mice in the model group were anesthetized and performed hysterectomy. The animals in the sham-operated group had abdominal cavity opened and only exposing the uterus. The changes of body weight were observed dynamically,and at the end of the fourth weeks. The concentration of serum estradiol was determined and histological structure of the ovaries was examined. Results The general status of all the mice after operation was good without obvious inflammation, and the incision healed completely. There was no significant difference in the body weight before operation among the mice, whereas the weight of model group mice was higher than the control group and sham-operation group at the end of the second,third and forth weeks(P< 0.05). The estradiol contents of the model group was significantly lower than that in control group and sham operation group(P< 0.01). The histological structure of ovaries in the control group and sham-operation group was normal,however the model group showed differences,such as irregular shape of the ovaries,changed number of mature follicles, loosely distributed granulosa cells, and apoptosis. Conclusions The mouse model of total hysterectomy established in our study can well simulate the clinical manifestations of ovarian dysfunction after operation, and is an ideal model for the study of complications after ovariectomy and screening of drugs.