OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

Microalgae possess high photosynthetic efficiency, robust adaptability, and substantial biomass, serving as excellent biological resources for large-scale cultivation. Malic enzyme (ME), a ubiquitous metabolic enzyme in living organisms, catalyzes the decarboxylation of malate to produce pyruvate, CO₂, and NAD(P)H, playing a role in multiple metabolic pathways including energy metabolism, photosynthesis, respiration, and biosynthesis. In this study, we identified the Scenedesmus quadricauda malic enzyme gene (SqME) and its biological functions, aiming to provide excellent target genes for the genetic improvement of higher plants. Based on the RNA-seq data from S. quadricauda under the biofilm cultivation mode with high CO₂ and light energy transfer efficiency and small water use, a highly expressed gene (SqME) functionally annotated as ME was cloned. The physicochemical properties of the SqME-encoded protein were systematically analyzed by bioinformatics tools. The subcellular localization of SqME was determined via transient transformation in Nicotiana benthamiana leaves. The biological functions of SqME were identified via genetic transformation in Nicotiana tabacum, and the potential of SqME in the genetic improvement of higher plants was evaluated. The ORF of SqME was 1 770 bp, encoding 590 amino acid residues, and the encoded protein was located in chloroplasts. SqME was a NADP-ME, with the typical structural characteristics of ME. The ME activity in the transgenic N. tabacum plant was 1.8 folds of that in the wild-type control. Heterologous expression of SqME increased the content of chlorophyll a, chlorophyll b, and total chlorophyll by 20.9%, 26.9%, and 25.2%, respectively, compared with the control. The transgenic tobacco leaves showed an increase of 54.0% in the fluorescence parameter NPQ and a decrease of 30.1% in Fo compared with the control. Moreover, the biomass, total lipids, and soluble sugars in the transgenic tobacco leaves enhanced by 20.5%, 25.7%, and 9.5%, respectively. On the contrary, the starch and protein content in the transgenic tobacco leaves decreased by 22.4% and 12.2%, respectively. Collectively, the SqME-encoded protein exhibited a strong enzymatic activity. Heterologous expressing of SqME could significantly enhance photosynthetic protection, photosynthesis, and biomass accumulation in the host. Additionally, SqME can facilitate carbon metabolism remodeling in the host, driving more carbon flux towards lipid synthesis. Therefore, SqME can be applied in the genetic improvement of higher plants for enhancing photosynthetic carbon fixation and lipid accumulation. These findings provide scientific references for mining of functional genes from S. quadricauda and application of these genes in the genetic engineering of higher plants.
Nicotiana/genetics* ; Photosynthesis/physiology* ; Malate Dehydrogenase/biosynthesis* ; Plant Leaves/genetics* ; Scenedesmus/enzymology* ; Carbon Cycle/genetics* ; Lipid Metabolism/genetics* ; Plants, Genetically Modified/metabolism*

The interaction between Mycobacterium tuberculosis and host, as well as the regulation of some signaling pathways in the host, were involved in pathogen latency in macrophages. microRNAs (miRNAs) regulate the gene expression and biological functions, indicating that miRNAs played a regulatory role in bacterial infections. However, whether the host's miRNAs were also involved in the process of Mycobacterium tuberculosis infection had not been thoroughly studied. This study infected macrophages with pathogenic Mycobacterium tuberculosis strain H37Rv and low virulence strain H37Ra to explore the functional miRNAs. By identifying the expression profile of miRNAs in host cells after infection, the expression of 17 miRNAs significantly changed (P < 0.05) in the human macrophage THP-1 infected with highly pathogenic H37Rv strain (Rv), H37Rv inactivated strain (Rv-), and non-pathogenic H37Ra (Ra) strains respectively, indicating that host miRNAs may be involved in the interaction of Mycobacterium tuberculosis and host. Meanwhile, 10 types of miRNAs showed significant differences in cells infected with pathogenic and non-pathogenic Mycobacterium tuberculosis, suggesting that host miRNAs may play an important role in the pathogenicity and intracellular survival of Mycobacterium tuberculosis. Further study had found that miR-449a, miR-502-5p, and miR-708 were downregulated in cells infected with Mycobacterium marinum. Overexpression of these three miRNAs displayed the significant inhibitory effect on the growth of Mycobacterium marinum, indicating that miRNAs played a pivotal role in the interaction between the host and Mycobacterium marinum. This study provided the new insights into the pathogenesis of Mycobacterium tuberculosis and the treatment of tuberculosis.

The population aging and the coming of the information era are accompanied with the growing incidence of spinal degenerative diseases, which result in heavy social and economic burdens. Under the guidance of the tendon-bone theory, rich experience has been accumulated in the prevention and diagnosis of spinal degenerative diseases with traditional Chinese medicine(TCM), which demonstrates unique advantages. China's government has placed people's health in the strategic position of development, providing a favorable environment for the realization of healthy aging. The Healthy China 2030 advocates special actions for healthy bones. As China is facing an important period of demographic transition, the Traditional Chinese Medicine for Bone Health Program has emerged, combining the needs of the national health strategy and the advantages of TCM. This paper discusses the background and significance of the program. According to the theory of five body constituents and the characteristics of musculoskeletal system diseases, this paper constructs a theoretical system of "tendon-meridian-muscle-bone-marrow" to explain the structure and function of the musculoskeletal system. From the holistic view of TCM, this system shows not only the structure and function of the musculoskeletal system but also the patterns of disease development and the mechanism of TCM treatment. The system facilitates the research on not only the comorbidities related to bone health but also the occurrence, development, and outcome of diseases. In the management of chronic degenerative diseases, attention should be paid to the establishment and improvement of the disease prevention and control system in addition to the disease treatment alone. Finally, this paper introduces the characteristic advantages of TCM in the whole process of prevention, diagnosis, treatment, rehabilitation, and health maintenance of spinal degenerative diseases, aiming to enrich the connotation of the tendon-bone theory, provide ideas and implementation strategies for TCM clinical practice, and ultimately achieve the effective management of the diagnosis and treatment of spinal degenerative diseases.
Humans ; Medicine, Chinese Traditional ; Spinal Diseases/prevention & control* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*

Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.
Animals ; Brain/growth & development* ; 5-Methylcytosine/metabolism* ; Mice ; Synapses/genetics* ; Proto-Oncogene Proteins/metabolism* ; DNA-Binding Proteins/metabolism* ; Dioxygenases/metabolism* ; Cognition/physiology* ; Gene Expression ; Mixed Function Oxygenases/metabolism* ; Epigenesis, Genetic ; Mice, Knockout ; Mice, Inbred C57BL

Objective To evaluate the effects of anterior cruciate ligament (ACL) reconstruction timing on the motor performance and proprioception by clinical evaluation as well as proprioception and motor performance tests on the patients more than 2 years after ACL reconstruction. Methods The patients who underwent ACL reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from January 2015 to January 2021 and met the inclusion criteria were followed up,and the postoperative data were collected retrospectively.Fifty-six patients who met the inclusion criteria were included in this study and categorized into two groups:early surgery (n=28,who underwent ACL reconstruction ≤3 weeks after injury) and delayed surgery (n=28,who underwent ACL reconstruction >3 weeks after injury).The basic information,clinical evaluation results,proprioception,and motor performance were compared between the two groups. Results The ACL return to sport after injury scale (ACL-RSI) score in the early surgery group was higher than that in the delayed surgery group [(68.68±22.04)scores vs. (55.82±24.87)scores,P=0.045].There was no difference in the range of motion of the knee joint,the positive rate of pivot shift test,or the scores of Tegner,Marx,Lysholm,knee injury and osteoarthritis outcome score (KOOS),and international knee documentation committee (IKDC) between the two groups (all P>0.05).Although there was no significant difference in range of motion of the knee joint between the two groups,the proportion of knee flexion and extension affected in the early surgery group was smaller than that in the delayed surgery group.Neither motor performance (isokinetic strength test,Y-balance test,and single-leg jump test) nor proprioception had difference between the two groups (all P>0.05). Conclusions Early ACL reconstruction outperformed delayed ACL reconstruction in improving the psychological health,emotions,and confidence in returning to sport,accelerating functional recovery of the patients.The timing of ACL reconstruction has no significant effect on the short-term postoperative knee stability,knee function,motor performance,or proprioceptive recovery of the patients.Early ACL reconstruction is recommended for improving the clinical outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Proprioception/physiology* ; Retrospective Studies ; Male ; Female ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Postoperative Period ; Time Factors ; Return to Sport ; Recovery of Function ; Knee Joint/physiopathology* ; Young Adult

Objective To evaluate the effects of knee flexor and extensor strength on the subjective function and motor performance of knees after anterior cruciate ligament reconstruction. Methods A total of 53 patients who underwent anterior cruciate ligament reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from June 2015 to June 2021 and met the inclusion criteria were enrolled in this study.The patients were followed up time for at least 2 years.An isometric muscle strength test system was used to measure the strength of bilateral quadriceps and hamstring muscles.The patients were grouped according to whether the limb symmetry index (LSI) of peak torque of quadriceps and hamstring muscle reached 85% at an angular velocity of 60°/s.Specifically,26 patients were classified into group A (LSI≥85%) and 27 patients were classified into group B (LSI<85%).The subjective function and motor performance of knees were compared between the two groups. Results In terms of subjective function of knees,the international knee documentation committee (IKDC) score (88.76±9.93 vs. 81.08±12.57,P=0.017) and knee injury and osteoarthritis outcome score (KOOS) (86.27±8.96 vs. 80.22±11.31,P=0.036) were different between groups A and B.There was no significant difference in Lysholm score [95.0 (79.8,100.00) vs. 86.00 (66.00,100.00),P=0.238],ACL return to sports after injury scale score (66.08±22.25 vs. 61.12±23.53,P=0.434),Marx score [6.00 (4.75,7.00) vs. 6.00 (4.00,7.00),P=0.805] or Tegner activity score [8.00 (4.00,12.00) vs. 4.00 (2.00,12.00),P=0.566] between the two groups.In terms of motor performance,the single-leg triple hop LSI (0.92±0.13 vs. 0.81±0.18,P=0.016) and single-leg crossover hop LSI (0.96±0.12 vs. 0.84±0.22,P=0.021) showed significant differences between groups A and B,while there was no significant difference in single-leg hop LSI (0.90±0.18 vs. 0.79±0.25,P=0.116) between the two groups.In addition,there was no statistical significance in proprioception [30°:8.83±4.66 vs. 10.73±4.63,P=0.143;45°:6.94±3.82 vs. 7.66±3.93,P=0.504;60°:4.10 (3.20,4.72) vs. 3.90 (2.30,5.20),P=0.493] or Y-balance test results [anterior LSI:0.98 (0.84,1.02) vs. 0.94 (0.86,0.98),P=0.328;posterolateral LSI:1.00±0.08 vs. 0.97±0.07,P=0.249;posteromedial LSI:1.00 (0.97,1.03) vs. 0.96 (0.93,1.03),P=0.179] between groups A and B. Conclusion The patients with good symmetry of quadriceps and hamstring muscle strength after anterior cruciate ligament reconstruction had better subjective function and movement performance of knees than the patients with poor symmetry,which was mainly reflected in the IKDC score,KOOS,single-leg triple hop,and single-leg crossover hop.
Humans ; Anterior Cruciate Ligament Reconstruction ; Muscle Strength/physiology* ; Male ; Quadriceps Muscle/physiology* ; Female ; Adult ; Anterior Cruciate Ligament Injuries/physiopathology* ; Hamstring Muscles/physiopathology* ; Knee Joint/physiopathology* ; Anterior Cruciate Ligament/physiopathology* ; Torque ; Knee/physiopathology*

Objective To investigate the clinical efficacy and safety of the Camrelizumab combined with Shenqi Fuzheng injection of advanced non-squamous non-small cell lung cancer(NSCLC).Methods Patients with advanced squamous NSCLC diagnosed and treated in the department of medical oncology of The First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2023 were selected as the study subjects,and all patients were treated with pemetrexed combined with carboplatin chemotherapy.On the basis of the chemotherapy regimen,patients were divided into the Camrelizumab group(treated with Carelizumab)and the Camrelizumab+SFI group(treated with Camrelizumab+SFI).The short-term and long-term efficacy were evaluated using objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),and overall survival(OS).Survival data were analyzed using Kaplan-Meier method.The occurrence of side effects the adverse drug reactions was evaluated according to the common terminology standard for adverse events(CTCAE 4.03).Results A total of 95 patients with advanced NSCLC were included in this study.Among them,48 patients were in the Camrelizumab group,and 47 patients were in the Camrelizumab+SFI group.The ORR of advanced non-squamous NSCLC patients in the Camrelizumab+SFI group and Carolizumab group were 59.57％and 45.83％,respectively(x2=1.799,P=0.180),with DCR of 78.72％and 58.33％,respectively(x2=4.569,P=0.033).The median PFS(8.87 months vs.6.30 months,P=0.001 7)and median OS(9.13 months vs.7.73 months,P=0.037)of patients in the Camrelizumab+SFI group were significantly higher than those in the Camrelizumab group.In addition,there was no significant difference in the incidence of adverse reactions between two groups(P＞0.05).Conclusion Camrelizumab combined with Shenqi Fuzheng injection can improve the disease control rate and prolong the PFS and OS of patients with advanced non-squamous NSCLC.

Objective:To explore our self-designed classification system of irreducible intertrochanteric fractures based on reduction stage and bone block position and to evaluate the reduction techniques guided by the classification system.Methods:A retrospective study was conducted to analyze the data of 115 patients with irreducible intertrochanteric fracture who had been admitted to Department of Orthopedics, Beijing Hospital from September 2014 to November 2022. There were 24 males and 91 females with a mean age of (80.9±11.0) years. The reduction for the fractures was divided into a diaphysis reduction stage (Phase Ⅰ) and a cortical reduction stage (Phase Ⅱ). Based on the relative positions of the intraoperative bone blocks, Phase Ⅰ was divided into an anterior and posterior interlocking type (Phase Ⅰa) and a distal bone block sinking displacement type (Phase Ⅰb) while Phase Ⅱ into a proximal lifting type (Phase Ⅱa), a posterior angulation type (Phase Ⅱb), a positive support type (Phase Ⅱc), and a negative support type (Phase Ⅱd). Depending on the difficulties encountered in different reduction stages, corresponding close reduction strategies (such as top rod support, percutaneous prying, and Joystick technique) were adopted to restore the proximal femoral neck shaft angle, anteversion angle, anterior medial cortex, and length of the affected limb before fixation with intramedullary nails. Recorded were the patient's surgical time, intraoperative bleeding, quality of postoperative reduction, fracture union time, and complications.Results:The surgical time for this group of patients was 70.0(60.0, 92.0) minutes, and the intraoperative blood loss 200.0 (170.0, 200.0) mL. According to the standards by Baumgaertner et al., the quality of postoperative reduction was evaluated as excellent in 103 cases and as good in 12 cases, with an excellent and good rate of 100.0% (115/115). Of the 115 patients, 86 were followed up for more than 6 months to reveal fracture union in all after a duration of 6.0 (4.0, 8.0) months. One patient died of an acute cardiovascular event in the hospital 5 days after surgery. Two patients lost their mobility within 3 months after surgery due to acute cerebral infarction. There was no internal fixation failure requiring secondary surgery or no incision infection.Conclusion:Guided by our self-designed classification system of irreducible intertrochanteric fractures based on the intraoperative reduction stage and the relative position of bone block, real time intraoperative fluoroscopy images can be used to effectively clarify the difficulty of fracture reduction in stages so that corresponding reduction strategies can be adopted, leading to fine clinical efficacy.

Objective:To establish a visualized nomogram which can predict the rate of 30-day complications in the elderly patients after hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 1,074 patients with hip fracture aged 60 years and over who had been admitted to Department of Orthopedics, Beijing Hospital from January 2010 to December 2017. There were 335 males and 739 females with an average age of (80.3±7.3) yeas, 529 intertrochanteric fractures of the femur (all fixed with intramedullary nails after closed reduction), and 545 femoral neck fractures (including 470 ones treated with artificial femoral head replacement and 75 ones treated with artificial total hip replacement). The duration between injury to operation was (6.2±3.7) d. After the complications within 30 days after surgery were recorded, the risk factors for postoperative complications were screened using the binary multi-factor logistic regression analysis. The visualized nomogram and calibration graph were established with the risk factors screened.Results:Of the 1,074 patients, 28.49% (306/1,074) suffered from 30-day complications. The multivariate regression analysis showed that age ( OR=1.050, 95% CI: 1.022 to 1.080, P=0.001), time from injury to surgery ( OR=1.043, 95% CI: 1.005 to 1.083, P=0.027), white blood cell count ( OR=1.093, 95% CI: 1.033 to 1.158, P=0.002), serum albumin level ( OR=0.930, 95% CI: 0.883 to 0.980, P=0.007), troponin I ( OR=195.983, 95% CI: 2.224 to 17,268.296, P=0.021), respiratory system comorbidities ( OR=2.020, 95% CI: 1.287 to 3.170, P=0.002),cardiovascular comorbidities ( OR=1.388, 95% CI: 1.098 to 1.754, P=0.006), and neurological system comorbidities ( OR=1.778, 95% CI: 1.346 to 2.349, P<0.001) were the risk factors for 30-day complications after surgery in elderly patients with hip fracture. Based on these risk factors, a nomogram was created, with an area under the curve of 0.714. The calibration graph showed that the incidence predicted was close to that measured. Conclusion:The present study has established a visualized nomogram which can predict the rate of 30-day complications in the elderly patients after hip fracture based on age, time from injury to surgery, white blood cell count, serum albumin levels, troponin I, and cardiovascular, respiratory and neurological complications.