Intervertebral disc degeneration (IDD) is the main cause of low back pain. Immune cells play an extremely important role in regulating the progression of IDD by interacting with nucleus pulposus (NP) cells and the extracellular matrix (ECM). Healthy NP tissue is a vascular-free and immune-privileged tissue that does not normally interact with macrophages. However, the establishment of neovascularization channels in damaged intervertebral discs has led to extensive cross-talk between NP and macrophages, with different results depending on microenvironmental stimuli. Based on this, this review reviewed the correlation between IDD and low back pain, summarized the source and function of macrophages, and discussed the possible regulatory mechanism between macrophages and discogenic pain. Finally, potential therapies targeting macrophages to delay IDD in recent years were also discussed, aiming to emphasize the important role of immunology in IDD and provide a new direction for the prevention and treatment of IDD.
Humans ; Intervertebral Disc Degeneration/complications* ; Macrophages/immunology* ; Low Back Pain/immunology* ; Nucleus Pulposus ; Animals ; Extracellular Matrix

Climate and land use changes may significantly impact the habitat distribution of Gastrodia elata, an endangered traditional medicinal plant. Accurately predicting its future potential suitable habitats is crucial for its conservation and sustainable development. This study integrates current distribution data of G. elata with 56 environmental variables and uses the MaxEnt model to predict changes in its suitable habitats under current climate conditions and four future climate scenarios(SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The results show that October precipitation and December minimum temperature are key environmental factors influencing its distribution. Under the current climate, optimal habitats for G. elata are concentrated in montane forest areas in Sichuan, Yunnan, Guizhou, and Hubei, which meet the species' requirements for understory growth. Across all future scenarios, the suitable habitat of G. elata consistently shows a stable northward shift, with a steady increase in suitable areas, extending to the middle and lower reaches of the Yangtze River and the Huang-Huai region, and even expanding into Liaoning, Jilin, and southern Heilongjiang. Land use analysis, taking into account the protection of arable land and the utilization of forest resources, indicates that by 2100, under future climate conditions, arable land in medium-to high-suitability areas is expected to increase by 30%-124%. While the conversion of non-suitable forest land into suitable habitats is projected to increase by 5%-52%, the growth of medium-to high-suitability areas within forests is relatively modest, ranging from 1% to 24%. These findings highlight the need to balance agricultural expansion with forest resource conservation to ensure the long-term sustainability of G. elata and provide scientific guidance for future suitable habitat management.
Ecosystem ; China ; Climate Change ; Gastrodia/growth & development* ; Conservation of Natural Resources ; Plants, Medicinal/growth & development*

L-tyrosine is one of the 20 amino acids that make up proteins and is an essential amino acid for mammals, often used as a nutritional supplement. The conventional methods for synthesizing L-tyrosine have some problems such as the production of many by-products, high requirements for production conditions, and environmental pollution. In this study, we designed and constructed a multi-enzyme cascade for the synthesis of L-tyrosine with alanine, glutamate, ammonium chloride, and phenol as substrates. Initially, the sources of glutamate oxidase, alanine aminotransferase, and tyrosine phenol lyase were screened and analyzed, which was followed by the identification of the rate-limiting enzyme in the reaction process. A colorimetric screening method was established, and the rate-limiting enzyme DbAlaA was engineered to enhance its activity by 40.0%. Subsequently, the reaction conditions, including temperature, pH, cell concentration, and surfactant and coenzyme dosages, were optimized. After optimization, the yield of L-tyrosine reached 9.93 g/L, with a alanine conversion rate of 54.90%. Finally, a feed-batch fermentation strategy was adopted, and the yield of L-tyrosine reached 56.07 g/L after 24 h, with a alanine conversion rate of 65.22%. This study provides a reference for the whole-cell catalytic synthesis of L-tyrosine and its industrialization.
Tyrosine/biosynthesis* ; Escherichia coli/metabolism* ; Tyrosine Phenol-Lyase/genetics* ; Multienzyme Complexes/metabolism* ; Fermentation

Objective:This study aimed to provide basic data for the prevention, diagnosis and treatment of pediatric viral myocarditis (VMC) in China through analyzing the epidemic characteristics and disease burden of pediatric inpatients with VMC from 2016 to 2021.Methods:We performed a descriptive statistical analysis to the age, genders, seasons, regions and hospitalization cost and days of pediatric VMC inpatients and the death. All of the information was obtained from 27 Children′s hospitals or Maternal and Child Health hospitals of 23 provinces of China from 2016 to 2021.Results:A total of 7 647 599 cases including 1 646 VMC inpatients were admitted into our study. The annual numbers of hospitalizations were 173, 227, 313, 301, 295 and 337, with the hospitalized constituent ratios being 14.9/100 000, 17.9/100 000, 23.0/100 000, 20.5/100 000, 26.5/100 000 and 26.4/100 000 from 2016 to 2021. In recent 6 years, the proportion of VMC hospitalizations had increased yearly ( P<0.001), and had associated with the onset age ( P<0.001). Aged 12-≤18 years owned the highest hospitalized constituent ratio. The Northeast of China owned the largest number of VMC inpatients, and the East second to it. Among the 1 646 VMC children, there were 68 deaths, with the hospitalized case fatality rate of 4.13%. There were no significant differences between genders, age, seasons, years and fatality rate of VMC inpatients. For the diseases burden, the median of hospitalization days of all VMC inpatients was 10 days (IQR 6, 21), and the median of hospitalization cost was 1 1 842.3 RMB (IQR 6 969.22, 19 714.78). The median of hospitalization days of deceased VMC children was only 1 day (IQR 1, 3), the median cost could be 8 874.03 RMB (IQR 5 277.94, 5 6 151.59). Conclusions:In this study, we found that proportion of hospitalization of VMC children increased year by year, adolescence might be a risk factor of VMC. The fatality of VMC inpatients could be up to 4.13%, and the death led to a huge economic burden of society, family and individuals.

Objective To investigate the curative effect of suture anchor(SA)repair combined with open reduction and internal fixation(ORIF)on patients with ankle joint fracture(AF)combined with deltoid ligament injury(DLI).Methods A total of 138 patients with AF combined with DLI admitted to our hospital from January 2020 to September 2022 were selected and divided into the control group(69 cases)and the observation group(69 cases)according to the random number table method.Patients in the control group were treated with ORIF,while patients in the observation group were treated with SA repair on the basis of the control group.The clinical efficacy,American Orthopedic Foot and Ankle Society(AOFAS)score,visual analogue scale(VAS)score,talus inclination angle,medial malleolar space of affected side,bone metabolic indexes[serum bone gla protein(BGP),β-collagen degradation product(β-CTX)]levels and the incidence of complications before and 3 months after treatment were compared between the two groups.Results The total effective rate in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Compared with before treatment,the talus inclination angle,medial malleolar space of affected side,VAS score,β-CTX level 3 months after treatment of patients in the two groups were reduced,while the AOFAS score and BGP level were increased,and the differences were statistically significant(P<0.05).After treatment,the AOFAS score and BGP level in the observation group were higher than those in the control group,while the talus inclination angle and medial malleolar space of affected side were smaller than those in the control group,and the VAS score and β-CTX level were lower than those in the control group,with statistically significant differences(P<0.05).The total incidence of complications in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion SA repair has a definite therapeutic effect on AF combined with DLI,which can improve patients' symptoms and promote the recovery of ankle joint function and bone metabolism.

Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.

This study aims to investigate the effects of Bushen Huoxue Decoction regulating adipose-derived stem cells(ADSCs)-exosomes(Exos) on the apoptosis of intervertebral disc nucleus pulposus cells(NPCs) and extracellular signal-regulated kinase(ERK) signaling pathway. Tert-butyl hydrogen peroxide(TBHP)-induced NPCs were divided into control, model, drug-containing serum, blank Exos, normal serum Exos, and drug-containing serum Exos groups. Cell viability and proliferation were examined by the CCK-8 assay and EdU staining, respectively. The cell cycle and apoptosis were evaluated by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin(IL)-1β, tumor necrosis factor(TNF)-α, and IL-6. The mRNA levels of aggrecan, collagen type Ⅱ alpha 1 chain(COL2A1), and ERK were determined by qRT-PCR, and the protein levels of aggrecan, COL2A1, and p-ERK were determined by Western blot. The results showed that compared with the model group, the treatments with drug-containing serum, blank Exos, and normal serum Exos enhanced the viability and proliferation of NPCs, decreased the proportion of cells in the G_0/G_1 phase, increased the proportion of cells in the S phase, reduced apoptosis, lowered the levels of IL-1β, TNF-α, and IL-6, up-regulated the mRNA and protein levels of aggrecan and COL2A1, and down-regulated the mRNA level of ERK and the protein level of p-ERK. Compared with the drug-containing serum, blank Exos, and normal serum Exos groups, the treatment with drug-containing serum Exos enhanced the viability and proliferation of NPCs, decreased the proportion of cells in the G_0/G_1 phase, increased the cells in the S phase, reduced apoptosis, lowered the levels of IL-1β, TNF-α, and IL-6, up-regulated the mRNA and protein levels of aggrecan and COL2A1, and down-regulated the mRNA level of ERK and the protein level of p-ERK. The results confirmed that the Exos secreted by ADSCs after treatment with Bushen Huoxue Decoction-containing serum promoted the proliferation of degenerated NPCs, inhibited apoptosis and the expression of inflammatory mediators, and promoted the production of proteoglycans and collagen, thus delaying the progression of intervertebral disc degeneration, the mechanism of which was related to the regulation of the ERK signaling pathway.
Intervertebral Disc Degeneration/drug therapy* ; Apoptosis/drug effects* ; Nucleus Pulposus/cytology* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Rats ; MAP Kinase Signaling System/drug effects* ; Rats, Sprague-Dawley ; Collagen Type II/metabolism* ; Humans ; Cell Proliferation/drug effects* ; Stem Cells/metabolism* ; Aggrecans/metabolism* ; Cell Survival/drug effects* ; Male ; Cells, Cultured ; Tumor Necrosis Factor-alpha/metabolism*

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens