(+)-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 investigate the safety and feasibility of the domestic SA-1000 single-port single-arm robot-assisted laparoscopic system in total hysterectomy.Methods Data from 16 patients who underwent total hysterectomy using the SA-1000 system at the Department of Obstetrics and Gynecology,The Second Affiliated Hospital of Naval Medical University,between Mar.2023 and Jan.2024 were retrospectively collected.Surgical parameters were analyzed.Postoperative pain was assessed using the visual analogue scale(VAS)at 24 h after surgery and before discharge.Incision cosmesis was evaluated 3-5 weeks postoperatively using the body image questionnaire(BIQ,score range 3-24).Results All 16 procedures were successfully completed using the SA-1000 system without conversion to open surgery,achieving a 100.0%procedural success rate.The mean whole surgery time was(234.40±56.24)min.The median robotic arm setup time was 8.0(4.0,13.5)min,and the median console operating time was 128.0(100.0,151.0)min.The median intraoperative blood loss was 100.0(100.0,200.0)mL.No perioperative complications,such as hemorrhage,infection,injury to adjacent organs(ureters,bladder,bowel),poor wound healing,or incisional hernia,were observed.The mean wound pain score at 24 h postoperatively was 3.81±1.64,decreasing to a median of 3.0(2.0,4.0)before discharge.The BIQ score assessed at 3-5 weeks postoperatively was 21.88±1.15.Conclusion The application of the domestic SA-1000 single-port single-arm robot-assisted laparoscopic system for total hysterectomy is safe and feasible,demonstrating favorable surgical outcomes.It holds promise for broader implementation and promotion in domestic medical centers.

Objective To analyze the application effect of multidisciplinary collaborative nursing based on the Information-Knowledge-Attitude-Practice(IKAP)theory in patients undergoing lobectomy via thoracoscopy.Methods A total of 168 patients undergoing lobectomy via thoracoscopy were se-lected,and randomly divided into control group and observation group using a random number table,with 84 patients in each group.The control group received routine nursing,while the observation group received multidisciplinary collaborative nursing based on the IKAP theory in addition to routine nurs-ing.The postoperative recovery,pulmonary function indicators[forced vital capacity(FVC),maxi-mum voluntary ventilation(MVV)and ratio of forced expiratory volume in the first second to forced vi-tal capacity(FEV1/FVC)],self-efficacy[General Self-Efficacy Scale(GSES)score]and self-man-agement ability[Chronic Disease Self-Management Questionnaire(CDSMQ)score]before and after intervention were observed and compared between the two groups.Results The observation group had shorter first ambulation time,first flatus time and length of hospital stay compared with the control group(P＜0.05).Before intervention,there were no statistically significant differences in FVC,MVV,FEV1/FVC,CDSMQ scores and GSES scores between the two groups(P＞0.05).After inter-vention,the observation group had higher FVC,MVV,FEV1/FVC,CDSMQ scores and GSES scores compared with the control group(P＜0.05).Conclusion Multidisciplinary collaborative nursing based on the IKAP theory can effectively promote the recovery process in patients undergoing lobec-tomy via thoracoscopy,improve postoperative pulmonary function,self-management ability,and self-efficacy,thereby enhancing the quality of rehabilitation.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective To explore the role and mechanism of exosomes derived from bone marrow mesenchymal stem cells(BMSCs)overexpressing transglutaminase 2(TGM2)in lactate-mediated oxidative stress-induced apoptosis in nucleus pulposus cells.Methods Twenty 6-week-old male SD rats(350±50 g)were used to extract nucleus pulposus cells.Lactic acid was utilized to establish a model of oxidative stress-induced apoptosis in primary nucleus pulposus cells.Lentiviral vectors carrying TGM2 were employed to transfect BMSCs to overexpress the protein,and then exosomes were extracted from the BMSCs and identified.Subsequently,to investigate the potential mechanisms of TGM2-overexpressing exosomes against oxidative stress-induced apoptosis in nucleus pulposus cells,flow cytometry was used to detect the production of reactive oxygen species(ROS),and Western blotting and immunofluorescence assay were applied to measure the expression levels of Bax,Bcl-2,Cleaved-Caspase3,p-PI3K,p-Akt,n-Nrf2,c-Nrf2 and HO-1,and Nrf2 nuclear translocation.The rate of oxidative stress-induced apoptosis in nucleus pulposus cells and changes in the PI3K/Akt/Nrf2 pathway were assessed in 4 groups of cells(n=3):control group,lactate treatment group,lactate+control exosome group,and lactate+TGM2-overexpressing exosomes group.Results Lactic acid of 10 mmol/L was found to be more effective in inducing oxidative stress-induced apoptosis in nucleus pulposus cells(P＜0.05).Both control BMSCs and TGM2-overexpressing BMSCs could produce exosomes and stably overexpress TGM2(P＜0.05,P＜0.01).Compared with the lactate treatment group,the nucleus pulposus cells in the lactate+TGM2-overexpressing exosome group and the lactate+control exosome group showed reduced apoptotic rates(P＜0.05),as well as decreased ROS level(P＜0.05).The lactate+TGM2-overexpressing exosome group exhibited better anti-apoptosis and ROS accumulation effects(P＜0.05).Additionally,the expression of Bax and Cleaved-Caspase3 was decreased(P＜0.05),that of Bcl-2 protein was increased(P＜0.05),the phosphorylation of PI3K/Akt was enhanced(P＜0.05),and both Nrf2 nuclear translocation and the expression of the antioxidant stress factor HO-1 were increased in nucleus pulposus cells.The lactic acid+TGM2-overexpressing exosome group showed stronger anti-apoptotic effects and activation of the PI3K/Akt/Nrf2 pathway(P＜0.05).Conclusion Exosomes derived from BMSCs overexpressing TGM2 can inhibit lactate-mediated oxidative stress-induced apoptosis in nucleus pulposus cells,and the mechanism may be related to the activation of the PI3K/Akt/Nrf2 pathway.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To analyze the current status,research hotspots and development trends in the field of immune responses in the microenvironment after spinal cord injury(SCI). Methods Literatrues about immune responses in the microenvironment after SCI were searched from CNKI and the Web of Science Core Collection,from inception to March,2024.VOSviewer and CiteSpace were used to conduct a vi-sual analysis of authors,countries,institutions,journals,co-cited references and keywords. Results A total of 152 Chinese and 455 English studies were included.The number of publications increased annually,and China and the United States were leading research efforts in this field.In the Chinese literature,Zhu Yue was the most prolific author,and China Medical University was the leading institution.In the English literature,Phil-lip Popovich was the most prolific and highly cited author,and Ohio State University was the leading institution.Journal of Neuroscience and Experimental Neurology were identified as key journals.The research hotspots in both languages focused on immune activation,inflammatory response and functional recovery.Researches on stem cell transplantation,macrophage and traditional Chinese medicine were particularly prominent in the regu-lation of immune responses after SCI. Conclusion Immune responses in the microenvironment have emerged as a central focus in SCI research.The emphasis of current researches is shifting from mechanistic exploration to the investigation of immunomodulatory strate-gies,with several cutting-edge technologies showing significant potential in this regard.Moving forward,increas-ing collaboration across regions and institutions are essential to promote information sharing,accelerate scientific progress,and facilitate clinical translation,ultimately enhance patient rehabilitation outcomes.

Objective To observe the effect of family-involved nursing model under the concept of rapid recovery in perioperative nursing for patients with pulmonary nodules. Methods A total of 180 patients with surgical treatment for pulmonary nodules were selected and randomly divided into control group and observation group, with 90 cases in each group. The control group was conducted with routine nursing, while the observation group was conducted with family-involved nursing model under the concept of rapid recovery. The time-related outcomes, preoperative anxiety, family burden, and postoperative training enthusiasm were compared between the two groups. Results The duration of chest tube indwelling and total hospital stay in the observation group were significantly shorter than those in the control group (P<0.05). After the intervention, the scores of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the Family Burden Scale (FBS) in the observation group were significantly lower than those in the control group (P<0.05). The level of postoperative training enthusiasm in the observation group was significantly higher than that in the control group (P<0.05). Conclusion The implementation of family-involved nursing model under the concept of rapid recovery can promote early recovery of patients with pulmonary nodules after surgery, alleviate preoperative anxiety, reduce family burden, and improve the enthusiasm of patients for postoperative rehabilitation training.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.