(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Objective: To evaluate the long-term effectiveness of an intelligent blood transfusion system in intraoperative blood management by comparing its performance with clinicians' decisions. Methods: A retrospective analysis of 26 760 surgical cases (2017-2024) was conducted, comparing pre- and post-implementation (2017-2019 vs 2020-2024) metrics, including transfusion prediction accuracy, rationality of blood use, and clinical outcomes. The system, powered by XGBoost, integrated patient demographics, laboratory results, and surgical data to predict red blood cell transfusion needs. Results: The intelligent blood transfusion systems achieved an accuracy of 80.62% in predicting transfusion necessity, significantly outperforming clinicians (24.83%, P<0.001). Its blood-use rationality rate was 83.92% vs 18.02% for clinicians (P<0.001). Post-implementation, major surgeries (grades Ⅲ-Ⅳ) increased while the requested blood units decreased. High physician compliance (>75%) correlated with 88.18% rationality. Conclusion: The intelligent blood transfusion system significantly improves the accuracy of transfusion decision-making, reduces excessive red blood cell use, optimizes perioperative transfusion management, and enhances the utilization of blood medical resources.

Background With the widespread application of ionizing radiation technology in non-medical fields, the number of non-medical radiation workers has steadily increased over the years. Individual dose monitoring serves as a crucial measure to safeguard the occupational health of non-medical radiation workers, as it can accurately identify occupational health risks and optimize radiation protection strategies. Objective To analyze the individual monitoring data of radiation workers from partial non-medical sectors in Shanghai from 2016 to 2023, to obtain the status of occupational radiation exposure and to provide a reference basis for non-medical radiation hygiene supervision and protection management. Methods The study subjects consisted of radiation workers from non-medical institutions in Shanghai who recieved individual dose monitoring at a Class-A radiation health technical service institution between 2016 and 2023. Under the Specifications for individual monitoring of occupational external exposure (GBZ 128-2019), thermoluminescence dosimetry was used for measuring personal dose equivalent, H_p(10), of various occupations encompassing industrial irradiation, industrial radiography, radioisotope production, accelerator operation, other industrial applications, education, and veterinary medicine. Kruskal-Wallis H test was used for comparison among multiple groups, Bonferroni method was adopted for pairwise comparison, and Mann-Kendall test was conducted for trend analysis to analyze the per-capita annual effective dose and its variation over time across different occupational categories of radiation workers. Results A total of 13728 person-times of non-medical radiation workers were monitored from 2016 to 2023, accumulating a collective effective dose of 3025.69 person-mSv. The per-capita annual effective dose M(P₂₅, P₇₅) was 0.14(0.08, 0.25) mSv. There were statistically significant differences in the per-capita annual effective dose of radiation workers in different years (H=874.826, P< 0.05). Similarly, significant variations were identified among various occupational categories (H=115.569, P< 0.05). Among them, the per-capita annual effective dose of radiological workers engaged in the production of radioactive isotopes was the highest, at 0.21(0.14, 0.32) mSv, followed by those in veterinary medicine, at 0.17 (0.11, 0.61) mSv; the difference between these two groups was not statistically significant (Z=1.231, P > 0.05), but both were significantly higher than those in other occupational categories (Z=3.913, 9.761, P<0.05). The veterinary medicine category had the highest proportion of monitored individuals with annual effective dose exceeding 1 mSv to the total number of monitored individuals(NR₁), reaching 17.12%, and the industrial radiography category showed the highest proportion of workers exposed to more than the annual investigation level 5 mSv to the total number of monitored individuals (NR₅), at 0.16%. Conclusion From 2016 to 2023, the overall individual doses of some non-medical radiation workers in Shanghai remain low, indicating well-controlled radiation levels in workplaces and low exposure risks. It is necessary to focus on radiation workers engaged in radioisotope production, veterinary medicine and industrial radiography.

Objective To explore the effect of targeted silencing wild-type p53-induced phosphatase 1(Wip1)on paclitaxel(PTX)chemosensitivity of ovarian cancer cell line A2780.Methods The ovarian cancer cell lines A2780 served as the research object,the stable cell line Wip1-sgRNA with low expression of Wip1 was constructed by infecting cell line A2780 with lentivirus(Wip1-sgRNA group),while the control cell line was NC-sgRNA(NC-sgRNA group).The cells were treated with PTX at appropriate time and divided into the Wip1-sgRNA+PTX group and NC-sgRNA+PTX group.The CCK8 method was used to detect the cell proliferation ability,the flow cytometry was used to detect the cell apoptosis,and the Transwell invasion assay was used to detect the cell invasion ability.Results Compared with the NC-sgRNA group,the expression lev-els of Wip1 mRNA and protein in the Wip1-sgRNA group were significantly down-regulated(P＜0.001).Un-der the condition of PTX gradient treatment for the same time,the cell survival rate of the Wip1-sgRNA group was significantly lower than that of the NC-sgRNA group(P＜0.001).The half maximal inhibitory concentration(IC50)of PTX in cells of the Wip1-sgRNA group at 48 h was significantly lower than that of the NC-sgRNA group(P＜0.001).Compared with the NC-sgRNA group,the proliferation ability of the Wip1-sgRNA group was significantly weakened(P＜0.001),the rate of cellular apoptosis was significantly in-creased(P＜0.001),and the number of transmenbrane cells was significantly decreased(P＜0.001).After PTX treatment,the proliferation ability was weakened compared with corresponding control groups,the rate of cellular apoptosis was significantly increased,and the number of transmenbrane cells was significantly de-creased;additionally,compared with the NC-sgRNA+PTX group,the cellular proliferation ability of the Wip1-sgRNA+PTX group was significantly weakened(P＜0.001),the rate of cellular apoptosis was signifi-cantly increased(P＜0.001),and the number of transmenbrane cells was significantly decreased(P＜0.001).Conclusion Wip1 gene silencing could increase the chemosensitivity of human ovarian cancer cell lines A2780 to PTX.

Objective To compare the clinical effects of minimally invasive percutaneous plate osteosyn-thesis(MIPPO)and interlocking intramedullary nail(IMN)internal fixation in the treatment of segmental tibial shaft fractures.Methods A total of 41 patients with segmental tibial shaft fractures in the Affiliated People's Hospital of Jiangsu University and Northern Jiangsu People's Hospital were selected as the study subjects,including 22 cases in the MIPPO group and 19 cases in the IMN group.All patients were followed up for 1 year.The clinical data such as the intraoperative bleeding volume,total blood loss volume(the difference value of hemoglobin before operation and on postoperative 1 d),postoperative early loading time,fracture healing time,incidence rate of postoperative complications and Johner Wruhs functional score in postoperative 1 year were compared between the two groups.Results Compared with the MIPPO group,the fracture heal-ing time in the IMN group was shorter[(17.39±2.10)weeks vs.(19.34±3.22)weeks,P＜0.05)],postoper-ative loading time was early[(6.93±1.04)weeks vs.(8.71±1.38)weeks,P＜0.05],total blood loss volume was greater[(32.89±6.55)g/L vs.(18.36±4.27)g/L,P=0.177)],but the intraoperative average blood loss had no statistical difference between the two groups[(99.33±31.62)mL vs.(87.34±24.15)mL,P=0.177].There was 1 case of malunion with a forward angle of 8° in the IMN group,1 case of infection,and the incidence rate of complications was 10.53％.In the MIPPO group,there were 3 cases of bone nonunion,2 ca-ses of infection and the incidence rate of complications was 22.73％.The complication incidence rate and the excellent and good rate of Johner Wruhs functional score in postoperative 1 year had no statistical difference between the two groups.Conclusion IMN could provide the stronger fixation,shorter fracture healing time,and early weight bearing functional exercise,which is the better choice for treatment of segmental tibial frac-tures.

Objective To investigate the effects of high-definition transcranial direct current stimulation(HD-tDCS)on the modulation of the H-reflex and M-wave during ankle dorsiflexion-plantar flexion fatigue tasks to provide direction for the application of HD-tDCS in mitigating neuromuscular fatigue.Methods Twenty healthy young male participants were recruited and randomly assigned to either the real stimulation or sham stimulation group,with 10 participants in each group.The intervention consisted of a 5-day single-blind HD-tDCS application(duration:20 min;intensity:2 mA;target:Cz).Baseline measurements of the H-reflex and M-wave under resting conditions,M-wave during maximal voluntary isometric contraction(MVIC)of the dorsiflexor muscle,and MVIC torque of the dorsiflexor and plantar flexor muscles were obtained.An ankle dorsiflexion fatigue task was performed to determine the time to achieve fatigue for the task.The same fatigue task was repeated and evaluated one day after the intervention.A repeated-measures two-factor(stimulation condition x pre/post fatigue)analysis of variance(ANOVA)was used to analyze the effects of independent variables on the mechanical properties of the muscles and α-motoneuron conduction characteristics.Results After fatigue,voluntary activation(VA),maximal H-reflex(Hmax),maximal M-wave(Mmax),and dorsiflexor and plantar flexor MVIC torques in both groups were significantly reduced compared with pre-fatigue levels(P＜0.05).However,compared to the real stimulation group,the sham stimulation group showed a more significant decline in VA and plantar flexor MVIC torque(P＜0.05).Conclusions A continuous 5-day HD-tDCS intervention can effectively increase α-motoneuron activity at the spinal segment.It can also exert an inhibitory effect on reducing information transmission capacity at the peripheral neuromuscular junction under the ankle dorsi-plantarflexion fatigue task.

Phlegm and dampness are endogenous,rise and fall with Qi,reach the limbs,diffuse the whole body,and form obesity.Regulating phlegm dampness with traditional Chinese medicine can realize the early prevention and treatment of obesity.Intestinal microbiota participates in a variety of human metabolic processes.Regulating intestinal microbiota is a new way to prevent and treat obesity.Taking the close relationship between intestinal flora and its metabolites,obesity and phlegm dampness theory as the breakthrough point,and based on the existing research results,this paper discusses the possible role of intestinal microbiota and its metabolites in the formation of phlegm dampness and the prevention and treatment of obesity,It is considered that the common intestinal microbiota and its metabolites of different individuals with obesity caused by phlegm dampness may be used as specific indicators to become the new micro identification basis of obesity phlegm dampness theory.It is proposed that intestinal microbiota and its metabolites will become the key point of obesity phlegm dampness theory research,which will provide a new explanation for obesity prevention and control research,and expand new research fields for the connotation of TCM phlegm dampness theory.

【Objective】 To explore the effectiveness of using donor plasma reinfusion to flush the leukoreduction system (LRS) chamber during the final reinfusion phase with the Trima Accel automated blood collection system in preventing the reduction of CD4+ and CD8+ T lymphocytes. 【Methods】 A longitudinal and cross-sectional study was designed. CD4+ count<200 cells/μL and CD8+ count<125 cells/μL were considered as the criteria for deficiency. Eighteen first-time platelet donors were followed up. The lymphocyte count was measured at 0, 3-6 and 7-14 times of blood donation in the last 300 days. 170 healthy blood donors who have not donated blood were selected as the control group. According to the cut-off point(October 2021), 88 blood donors who mainly used automatic blood collection system to donate platelet apheresis in the last 365 days(median blood donation times ≥17.5)were divided into three groups(A, B and C)and blood samples were obtained. The time for Groups A, B and C started donating platelet apheresis were as follows: Group A: before October 2019, Group B: from October 2019 to September 2021, Group C: after October 2021. Blood samples were analyzed to obtain blood counts including CD4 + and CD8 + T lymphocytes. Blood samples were analyzed to obtain blood cell counts including CD4+ and CD8+ T lymphocytes. Through a comparative analysis, this study aimed to determine if there are any statistical differences in the detection indices between the follow-up groups with varying frequencies of blood donation, the control group, and groups A, B, and C. This approach was employed to infer the efficacy of donor plasma reinfusion in flushing the leukoreduction system (LRS) chamber for preventing the decline of CD4+ and CD8+ T lymphocytes. 【Results】 Eighteen first-time blood donors who were converted to regular platelet apheresis donors did not show a decrease of CD4 + and CD8 + T lymphocytes in the 5 th and 11 th blood donation (median number of blood donation), and there was no significant difference between the above indexes and those in the 0 th blood donation. Among the previous frequent blood donors, the CD4+ and CD8+ T lymphocyte counts in Group B and Group C are both higher than the standard value, showing no statistical difference from the control group. Among regular blood donors, the CD4+ and CD8+ T lymphocyte counts in groups B and C were higher than the criteria values, and had no statistical difference compared to the control group.The CD4+ T lymphocyte count in Group A was normal, with only one donor in Group A having a CD8+ T lymphocyte count below 125 cells/μL. This donor has donated 281 times of platelet apheresis, and the group he belongs to has started blood donation 2-21 years(median of 5 years) before the adjustment of reinfusion mode. The CD4+ and CD8+ T lymphocyte counts in Group A showed significant differences compared to the control group, with median counts (Group A/Control Group) of 359/521 and 257/372, respectively, P<0.001. In Group A, 0%(0/35) had a CD4+ count below 200 cells/μL, and 2.85%(1/35) of donors had a CD8+ count below 125 cells/μL, which was far lower than the proportion of CD4+ and CD8+ T cell deficiency found in regular apheresis donors by John M. Gansner and Mahboubeh Rahmani. The study showed that the adjustment of the plasma reinfusion mode did not further reduce the T lymphocyte counts in blood donors, but instead further restored the T lymphocyte counts in regular blood donors. This indicated that after the adjustment of plasma reinfusion mode, blood donors might not have lost CD4+ and CD8+ T lymphocytes during blood donation, or only lost a small amount, and can recover even if they donate platelet apheresis frequently. 【Conclusion】 Trima Accel automated blood collection system has a good effect on preventing CD4 + and CD8 + T lymphocytes from being reduced by flushing the LRS chamber with donor plasma.

Background Individual monitoring of occupational external exposure is an essential part of the occupational health management of radiation workers, and is an important basis for the evaluation of individual absorbed dose and the diagnosis of occupational radiation diseases. Continuous participation of monitoring service providers in intercomparison is a fundamental quality assurance for routine monitoring, which can identify problems and improve them in time. Objective Taking the Laboratory of Radiation Protection in Shanghai Institute of Preventive Medicine as an example, to evaluate the performance of an individual occupational external dose monitoring system in the laboratory, identify influencing factors of the monitoring results, and provide a basis for improving the quality of daily monitoring by analyzing the process and results of a national intercomparison of individual dose monitoring. Methods According to the Testing criteria of personnel dosimetry performance for external exposure (GBZ 207-2016), and the relevant requirements of Class II (photon) inspection, a total of 20 groups of blind sample dosimeters were measured for four consecutive years from 2018 to 2021. The radiation energy source of each group was identified, and related personal dose equivalent H_p(10), the uncertainty of measurement results, and the deviation between the reported value and the reference value were calculated. The national intercomparison process and results of individual dose monitoring were also analyzed. Results The energy sources of the blind samples in the tested laboratory for four years were N100 or Cs-137. The reported dose values of the blind samples were 0.57-4.61 mSv, the combined uncertainties were 0.043-0.365 mSv, the expanded uncertainties (k=2) were 0.09-0.73 mSv, and the relative expanded uncertainties (k=2) were 13.8%-16.4%. The single-group performance ∣P_i∣ of 20 sets of blind samples in the four years was ≤0.10, the yearly comprehensive performance of 5 sets of blind samples was ≤0.10, and the yearly Q score of the test report was >15 points. The laboratory achieved excellent results in the national intercomparison of individual dose monitoring in four consecutive years, except the Q value not reaching full score. Conclusion The laboratory exhibits standardized data processing of individual dose monitoring, generates accurate and reliable results, and meets the requirements of relevant national standards; but it should continue to participate in the national intercomparison of individual dose monitoring, strengthen the angular response research of energy identified dosimeter, improve the monitoring ability of low-dose X-rays, analyze the key points of reducing the uncertainty of measurement results, and continuously improve the monitoring ability.

Objective To investigate the quality control and protection level of medical electron linear accelerators in Shanghai, China. Methods The startified random sampling method was used to cover tertiary, secondary and ungraded hospitals, and a total of 30 medical electron linear accelerators in 15 hospitals were tested for quality control and protection level according to relevant standards. Results Five medical electron linear accelerators failed the quality control test, with an overall inspection pass rate of 83.3% and a re-inspection pass rate of 100%. The pass rate of flatness of square X-ray irradiation field (5 cm × 5 cm)-(30 cm × 30 cm) was 83.3%, the pass rate of symmetry of square X-ray irradiation field was 96.7%, and other indices were qualified. All medical electron linear accelerator rooms passed the protection test. Conclusion The protection of medical electron linear accelerator rooms in Shanghai meets the requirements of national standards, and some indices do not meet the requirements of national standards in the preliminary inspection. The quality control of medical electron linear accelerators should be further strengthened to ensure the treatment effect of patients.