In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective:To study the experience and efficacy of treating the isolated left vertebral artery (ILVA) during total aortic arch replacement combined with stent-trunk surgery in patients with Stanford type A aortic dissection (TAAD) combined with ILVA.Methods:The clinical data of 21 patients with TAAD combined with ILVA from July 2017 to March 2022 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All patients were treated with ILVA-left common carotid artery transplantation and total arch replacement combined with stent-trunk surgery under moderate hypothermia cardiopulmonary bypass and selective cerebral perfusion (SCP). Among them, aortic root repair surgery was in 15 cases, Bentall surgery in 6 cases, coronary artery bypass grafting performed simultaneously in 2 cases. The surgical details, postoperative complications and length of stay were recorded. The patients were followed up 1 and 12 months after surgery for CTA examination to observe the patency of transplanted ILVA. The follow-up was performed until October 1, 2022, and survival, aorta-related death and ILVA patency rate were recorded.Results:Three hundred and thirty-five TAAD patients were admitted during the same period, including 21 (6.27%) with ILVA. ILVA was reconstructed successfully in all patients. No complications related to ILVA were observed. Three cases died during the perioperative period: 1 case had preoperative myocardial infarction due to coronary artery involvement and the CPB could not be removed after operation; 1 case died of postoperative liver and renal failure due to severe organ hypoperfusion; 1 case suffered from postoperative acute renal failure and died of low cardiac output. The patients did not experience damage to the vagus nerve or recurrent laryngeal nerve, lymphatic leakage, chylothorax, ILVA thrombosis, paraplegia or cerebral vascular complications. The other 18 patients recovered and discharged from hospital. The median duration of follow-up was 30 (6 to 62) months. During the follow-up, aortic-related death did not observe, ILVA was unobstructed, and there were no manifestations of anastomotic stenosis or arterial stenosis.Conclusions:ILVA is a supra-aortic trunk variant, it is not so rare. ILVA may pose additional difficulties during total arch replacement surgery. The clinical effect of prior reconstruction of ILVA by ILVA-LCCA transposition is satisfactory, and it may be a simple and efficient method to complete reconstruction and optimize arch surgery before cardiopulmonary bypass.

Aim To study the effect of liraglutide on myocardial metabolites and related metabolic pathways in diabetic cardiomyopathy(DCM)rats.Methods Among 60 SPF male SD rats aged 3 weeks,10 rats were randomly selected as normal control group(n=10),and the remaining 50 rats were established by peritoneal injection of streptozoto-cin combined with high-sugar and high-fat diet for DCM rat model.A total of 36 rats were successfully modeled for DCM and randomly divided into DCM model group(DCM group,n=12),low-dose liraglutide treatment group(LL group,n=12)and high-dose liraglutide treatment group(HL group,n=12).Rats in LL group(100 μg/kg)and HL group(200μg/kg)were given intraperitoneal injection of liraglutide once a day.And after 12 weeks of intervention,the rats were killed under anesthesia after echocardiography to detect cardiac function,and the heart tissues were taken for metabolomics detection.The differential metabolites and related pathways that may be related to liraglutide improving myocardial metab-olism in DCM rats were screened and enriched.Results Compared with normal control group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in DCM group were significantly decreased,and the ra-tio of early to late diastolic mitralflow velocities(E/A)was significantly increased(P＜0.05).Compared with DCM group,LVEF and LVFS in LL group and HL group were significantly increased,and E/A ratio was significantly decreased(P＜0.05),suggesting that the impairment of left ventricular systolic and diastolic function in LL group and HL group was significantly alleviated.395 metabolites were detected by metabolomics,among which 239,116 and 187 different metab-olites and 13,6 and 20 metabolic pathways were enriched in DCM group and normal control group,LL group and DCM group,HL group and DCM group.In the above three groups,29 key differential metabolites were identified related to 3 metabolic pathways including choline metabolic pathway,caffeine metabolic pathway and valine,leucine and isoleucine bi-osynthesis pathway,among which choline metabolic pathway had the most significant differences.Conclusion These results indicated that liraglutide can ameliorate cardiac dysfunction in DCM rats through improving myocardial metabolism in which choline metabolism pathway may play a key role.

Objective:To assess the effects of the scanning parameters of cone beam computed tomography(CBCT)on image quality,positioning error and additional radiation dose for patients with cervical cancer after tube voltage was reduced,so as to explore scanning conditions that was suitable to patients with cervical cancer.Methods:Seventy-two patients with cervical cancer who received radiotherapy in Deyang People's Hospital from January 2020 to August 2022 were selected.According to different scanning parameters,they were divided into low-dose group A(120 kV,154.4 mAs),low-dose group B(120 kV,228.8 mAs)and conventional group[adopted business-supplied scan sequences(120 kV,675.8 mAs)].The CBCT scan image was obtained by decreasing the tube voltage and tube current,and reducing scanning angle.The registration results of positioning error of low-dose group A,B and conventional group on three directions included left and right(x-axis),head and foot(y-axis)and abdominal and back(z-axis)were respectively obtained,and the results were analyzed by variance analysis.The Catphan503 phantom of X-ray volumetric imaging(XVI)was used to measure the image quality of the corresponding 3 groups,and the further comparison was conducted.Results:There were no significant differences between the three groups in the scanning parameters on x,y and z axis directions for positioning error of patients with cervical cancer(P＞0.05).The scanning times of low-dose group A and B were approximately 1 minute,and the scanning time of conventional group was approximately 2 minutes.The noises of low-dose group A and B,and conventional group were respectively 36.51％,26.09％and 18.37％,and the radiation dose that was generated by CBCT image scanning in group A was correspondingly reduced.Conclusion:The reductions of scanning speed and collimator size of CBCT scanning parameters do not affect the positioning error and image quality,and it can decrease the scanning time and additional radiation dose of patients in undergoing radiotherapy.

Objective:To analyze the efficacy and safety of integrase inhibitor-based single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and lamivudine/dolutegravir (3TC/DTG) in the treatment-na?ve patients with acquired immunodeficiency syndrome (AIDS).Methods:This study was a retrospective cohort study. The clinical data of treatment-na?ve AIDS patients initiating anti-retroviral therapy (ART) with B/F/TAF or 3TC/DTG and on ART for greater than or equal to 24 weeks from October 2020 to July 2023 in Shanghai Public Health Clinical Center, Fudan University were collected. The baseline human immunodeficiency virus (HIV)-1 RNA, CD4 + T lymphocyte counts at baseline and 12 weeks of treatment, and the rates of virological suppression and virological failure at 24 weeks of treatment, and levels of total cholesterol, serum creatinine, uric acid before and after treatment were compared between the B/F/TAF group and 3TC/DTG group. Independent sample t test, corrected t test, Mann-Whitney U test, Wilcoxon signed rank test, chi-square test were used for statistical analysis. Results:Among 189 treatment-na?ve AIDS patients, 141 cases were in B/F/TAF group and 48 cases in 3TC/DTG group. The HIV-1 RNA level at baseline was 1.77(0.78, 4.52)×10 5 copies/mL in the B/F/TAF group and 0.97(0.24, 2.20)×10 5 copies/mL in the 3TC/DTG group. There was a statistically significant difference between the two groups ( U=2 221.00, P=0.006).There were 77.3%(109/141) patients on B/F/TAF achieved complete virological suppression with no virological failure at week 24, and 85.4%(41/48) on 3TC/DTG achieved complete virological suppression with one (2.1%) virological failure at week 24. At 12 weeks of treatment, 92.2%(130/141) of the patients in the B/F/TAF group and 85.4%(41/48) of the patients in the 3TC/DTG group had an increase in CD4 + T lymphocyte count by more than 30% compared with baseline. The proportion of CD4 + T lymphocyte count increased by more than 100/μL from baseline in the B/F/TAF group was 67.4%(95/141), and that in the 3TC/DTG group was 52.1%(25/48). There were no significant differences between the two groups ( χ2=1.91 and 3.61, respectively, P=0.167 and 0.733).The levels of total cholesterol ( W=2 036.00, t=-5.42, respectively), serum creatinine ( W=1 098.00, 234.00, respectively), uric acid ( W=2 188.00, 299.00, respectively) and the proportion of patients with mild to moderate renal insufficiency ( χ2=22.29, 8.22, respectively) in the B/F/TAF group and 3TC/DTG group after 24 weeks of treatment were significantly higher than those before treatment (all P<0.01). Conclusions:Both B/F/TAF and 3TC/DTG are effective in terms of virological suppression and immunological recovery and have good safety profiles in treatment-na?ve patients with AIDS.

Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.

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.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.

BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.