Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice / 中国实验方剂学杂志

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg-1）， and low-dose （4.78 g·kg-1·d-1）， middle-dose （9.56 g·kg-1·d-1）， and high-dose （19 g·kg-1·d-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

Comparison on Ameliorating Effect of Arisaematis Rhizoma and Arisaematis Rhizoma Preparatum on Allergic Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Mechanism of Dihuangyin in Treatment of Mice with Atopic Dermatitis by Regulating JAK1/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and potential mechanism of Dihuangyin on 2， 4-dinitrochlorobenzene （DNCB） -induced model mice with atopic dermatitis （AD）. MethodA mouse model with AD was established by repeatedly stimulating the back skin of mice with DNCB. After successful modeling， the mice were randomly divided into model group， Runzao group （0.78 g·kg-1）， and high， medium， and low dose （40.30， 20.15， and 10.08 g·kg-1） groups of Dihuangyin， with 12 mice in each group， and the blank group consisted of 12 mice， 72 in total. The administration groups were given the corresponding liquid by dose， and the blank group and model group were given the same dose of pure water by intragastric administration， once a day. The skin lesions and scratching times of mice were observed after continuous administration for two weeks. The back skin lesions of mice were stained with hematoxylin-eosin （HE） and toluidine blue to observe the pathology. The contents of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， and interferon-γ （IFN-γ） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of IFN-γ， IL-4， IL-6， Janus kinase 1 （JAK1）， and transcriptional activator 3 （STAT3） in skin lesion tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of JAK1， phosphorylation（p）-JAK1， STAT3， and p-STAT3 proteins in skin lesion tissue were detected by Western blot. ResultCompared with the blank group， the back skin of the model group showed large-scale scab， dryness， erosion， hypertrophy with scratching， epidermal hyperplasia with hyperkeratosis and parakeratosis， hyperacanthosis with edema， and a large number of mast cell infiltration in the dermis， some of which were degranulated. The contents of IgE， IL-4， IL-6， and IFN-γ in the serum of mice were significantly increased （P<0.01）， and the protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly increased （P<0.01）. Compared with the model group， only a small amount of dryness and desquamation were observed in the back skin of mice in each administration group， and cell edema was reduced. The inflammatory infiltration was significantly reduced， and the number of mast cell infiltration was significantly decreased. The serum IgE， IL-4， IL-6， and IFN-γ of mice were decreased to varying degrees （P<0.05， P<0.01）. The protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly decreased， and the effect of high dose group of Dihuangyin was the best （P<0.01）. ConclusionDihuangyin can improve skin lesions and pruritus in mice with AD， and its mechanism may be related to the effective regulation of cytokines on the helper T cells （Th1）/Th2 axis by interfering with the JAK1/STAT3 signaling pathway and affecting skin barrier function.

Change and continuity: On the 9th UICC/IASLC/AJCC TNM staging system for thymic tumors / 中国胸心血管外科临床杂志

@#The announcement of the 9th edition of TNM staging system for thymic tumors was one of the highlights at the World Conference on Lung Cancer 2023. The revision, based on a larger and more detailed database, provides changes and confirmation from the last system. The 9th edition of TNM staging system aims to balance statistical significance and clinical feasibility. The birth of an improved TNM staging system heralds the changes that will follow in clinical practice and scientific research.

Improvement of Skin Barrier and Anti-inflammatory Mechanism of Huangliansan on Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect of Huangliansan on atopic dermatitis （AD） model mice induced by 2， 4-dinitrochlorobenzene （DNCB）. MethodA total of 42 male BALB/c mice were randomly divided into normal group， model group， hydrocortisone group， low， medium， and high-dose groups （0.3， 0.6， 1.2 g·kg-1） of Huangliansan oil， and water extract group （0.6 g·kg-1） of Huangliansan. In addition to the normal group， DNCB was applied on the back of mice in other groups to establish the AD model. On the 15th day after DNCB stimulation， each group was given the corresponding drug or solvent， and the changes in skin lesions， dermatitis score， and frequency of scratching were observed and recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the skin and spleen. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA levels of filaggrin （FLG）， lorophane （LOR）， and involucrin （IVL） in skin， as well as immunoglobulin E （lgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interferon-γ （IFN-γ） in spleen. ResultCompared with the normal group， the model group showed symptoms of skin swelling and scab， and the score of dermatitis， the frequency of scratching， and the spleen index were increased （P<0.05）. The expression levels of FLG， LOR， and IVL in skin tissue were significantly decreased （P<0.01）， and the mRNA expressions of IgE， IL-4， IL-6， IL-1β， and TNF-α in the spleen were significantly increased， while the expression level of IFN-γ was significantly decreased （P<0.01）. Compared with the model group， the symptoms of skin erythema， scaly， and scab of mice in each drug group were alleviated to varying degrees， and the score of dermatitis， the frequency of scratching， and the spleen index were decreased （P<0.05， P<0.01）. In addition， the expression levels of FLG， LOR， and IVL in the skin of mice in the drug group were increased （P<0.05， P<0.01）， and the mRNA expression of IgE， IL-4， IL-6， IL-1β， and TNF-α in spleen were decreased. IFN-γ was increased （P<0.05， P<0.01）， and the lesions of the skin and spleen were improved to varying degrees. The medium-dose group of Huangliansan oil and hydrocortisone group had the most obvious manifestations （P<0.05， P<0.01）. The indexes in the medium-dose group of Huangliansan oil were better than those in the water extract group of Huangliansan. ConclusionHuangliansan may improve the expression level of skin barrier protein， inhibit the expression of helper T cell 2 （Th2）-related inflammatory factors， increase the expression of helper T cell 1 （Th1） inflammatory factors， restore the skin barrier function and Th1/Th2 balance in the spleen， regulate the inflammatory response in the spleen of AD mice， and thus relieve AD. Huangliansan oil is more effective than water extract.

Heridas de guerra en el Perú del siglo XIX: la lesión ocular de Andrés Avelino Cáceres / War wounds in nineteenth century Peru: the eye injury of Andrés Avelino Cáceres

RESUMEN Andrés Avelino Cáceres (1836-1923) fue un destacado político y militar peruano que ocupó la presidencia en dos periodos y lideró al ejército peruano durante la Guerra del Pacífico, por lo que es considerado un héroe nacional. Al inicio de su carrera militar, durante el sitio a la ciudad de Arequipa en 1858, sufrió una lesión ocular cuya cicatriz se observa en las fotografías que se le tomaron posteriormente a lo largo de su vida, lo que hizo que fuera apodado "El Tuerto" aunque al parecer su agudeza visual estuvo indemne. En este trabajo describiremos las circunstancias en las que se produjo la lesión oftálmica de Andrés Avelino Cáceres, las secuelas que pudo tener este traumatismo oftálmico y el tratamiento médico que pudo haber recibido, en base al propio relato del héroe y a las imágenes suyas que se conservan.

ABSTRACT Andrés Avelino Cáceres (1836-1923) was a prominent Peruvian politician and military man who held the presidency for two terms and led the Peruvian army during the Pacific War, for which he is considered a national hero. At the beginning of his military career, during the siege of the city of Arequipa in 1856, he suffered an eye injury whose scar can be seen in the photographs that were taken of him later throughout his life, which led to him being nicknamed "El Tuerto". We will describe the circumstances in which the ophthalmic injury of Andrés Avelino Cáceres occurred, the consequences that this ophthalmic trauma could have had and the treatment he could have received, based on the hero's own story and the images of him that are preserved.

Theodor Kocher (1841-1917) and his outstanding contributions to surgery

Theodor Kocher (1841-1917), an exceptional Swiss surgeon who described a technique for the safe removal of enlarged thyroid unraveled the true function of this endocrine gland but also made significant contributions to many other fields of surgery. Kocher was the first surgeon awarded the Nobel prize in Physiology and Medicine in 1909 for his work on the physiology, pathology, and surgery of the thyroid gland. He was professor and clinical director at Insel Hospital during 45 years. Kocher created the prominent Surgeon's School in Bern. He was the first president of the International Society of Surgery in 1903 and the founding president of the Swiss Society of Surgery in 1913.

Theodor Kocher (1841-1917), excepcional cirujano suizo que describió una técnica para la extirpación segura del agrandamiento del tiroides y desentrañó la verdadera función de esta glándula endocrina, pero también hizo importantes aportaciones a muchos otros campos de la cirugía. Kocher fue el primer cirujano galardonado con el premio Nobel de Fisiología y Medicina en 1909 por sus trabajos sobre la fisiología, patología y cirugía de la glándula tiroides. Fue profesor y director clínico del Hospital Insel durante 45 años. Kocher creó la destacada Escuela de Cirujanos de Berna. Fue el primer presidente de la Sociedad Internacional de Cirugía en 1903 y el presidente fundador de la Sociedad Suiza de Cirugía en 1913.

olf413 Gene Controls Taste Recognition, Preference and Feeding Activity in Drosophila melanogaster

Recognition and responsiveness to food taste becomes a crucial event in foraging and feeding behaviour of an organism. Adjusting the feeding behaviour through a sophisticated and robust taste system is critical to fulfil their nutritional needs and facilitate its survival in environment. Palatability of food sources depends on the sensory and motor cues provided by the brain, in co-ordination with the other body systems to enable decisive feeding. Drosophila melanogaster is an apt model organism to decipher these behavioural paradigms. Octopamine a neurotransmitter, is required in regulation of feeding behavioural responses. olf413, a paralogue of TH, is a gene predicted for its involvement in octopamine biosynthesis. The biological function of this gene is yet to be unravelled. Here we propose this gene function in taste recognition, food preference and feeding activity. We test the olf413 loss of function mutants for food preference between two fruit extracts using CAFE and horizontal box methods. In our study we have used olf413 gene disruption strain, olf413MI02014 homozygous and in transheterozygous condition with another allele isolated in our lab, olf413SG1.1. The results show that olf413 mutants display a severe phenotype in feeding behaviour and there is an allele specific phenotypic distinction between the two strains. Thus implying that olf413 gene function is required for taste recognition, starvation driven initiation and execution of feeding behaviour of the flies.

Opinion of Nurses on SWOT and Areas of Investment in Nursing

Nursing is the largest group in the health sector accounting for approximately 59 percent of health care professionals. Nurses play a key role in rendering preventive, promotive and rehabilitative health care services. The work of nurses at all stages of their careers and at every level of prac- tice is essential in achieving Sustainable Development Goals (SDGs). Hence an opinion on SWOT in nursing and the priority areas of investment was undertaken among nurses. A quantitative research approach and a descriptive survey design were used. This study was conducted among nurses working in educational institutions and hospitals. A non-probability convenient sampling technique and snowball sampling were used. The tool consisted of items to elicit demographic data of nurses and an opinion scale to elicit the nurses'#39; opinion about SWOT in Nursing. A rating scale was used to rate the opinion about priority areas of investment in Nursing. A Google form was developed and circulated to the nurses. A total of 213 responses were received. Incomplete responses were deleted and finally, 195 responses were included for final analysis. Both de- scriptive and inferential statistics were used. Permission from IEC and informed consent were obtained. Confidentiality was maintained. The results revealed that the majority of the nurses had high opinion by having agreement with the factors of SWOT in nursing and had high priority in the areas of investment.

The proportion of Th17 cells in patients with systemic sclerosis: a Meta-analysis / 中华风湿病学杂志

Objective:To clarify peripheral Th17 level in SSc patients and its correlation with disease.Methods:Chinese databases CNKI, CBM, Wanfang and VIP, and English databases PubMed, EMBASE, Web of Science, Cochrane Library and Science Direct were searched to collect a case-control study on the content of Th17 cells in peripheral blood of patients with SSc. The papers published when the database was first developed in 25 February 2021. Meta-analysis was conducted using Stata 12.0 software, and I2 and Egger tests were used to evaluate the heterogeneity and publication bias between studies. Results:A total of 26 case-controls were included in the study, including 1 160 patients with SSc and 778 healthy controls. Overall, the percentage of Th17 cells in SSc patients was higher than in healthy controls [SMD(95% CI)=1.85 (1.33, 2.38), P<0.001], which was most significant in IL-17 +Th17 concentration [SMD(95% CI)=1.88 (1.28, 2.48), P<0.001]. As for disease activity, the proportion of Th17 cells in active SSc patients was much higher than those of patients in remission [SMD(95% CI)=1.92 (1.12, 2.71), P<0.001]. SSc patients had a reduced Th17 level after receiving DMARDs treatment [SMD(95% CI)=-0.74 (-1.05, -0.42), P=0.029]. Conclusion:The number of Th17 cells increase significantly in the peripheral blood of patients with SSc, and is related to disease activity. DMARDs can be used to treat this disease by downregulating Th17 levels.

The spirit of the Party′s "20th Congress" illuminates the development direction of orthopedics in China / 中华创伤杂志

The 20th National Congress of the Communist Party of China held in 2022 draws a blueprint for China′s future development, which is of epoch-making historical and political significance. The spirit of the congress has provided a clear direction and guidance for the high-quality development of orthopedics in China. The orthopedics in China gains significant progress, but there still remain many problems, for which the solution needs a guiding light. The "six persistences" proposed in the report of the congress for the development of orthopedics in China lights the voyage forward. Guided by the spirit of the congress, let us orthopedic surgeons set sail, cut the waves, and strive to write a new chapter in the development of orthopedics in China!

Investigation on the incidence of IRIS in HIV patients with TB infection and its relationship with Th17/Treg, CD4 + T lymphocyte levels / 中国医师杂志

Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.

Effect of T helper 1 to T helper 2 ratio on the prognosis of patients with multiple myeloma / 白血病·淋巴瘤

Objective:To investigate the effect of T helper 1 (Th1) to T helper 2 (Th2) ratio (Th1/Th2) on the prognosis of patients with multiple myeloma (MM).Methods:The clinical data of 168 MM patients who were newly diagnosed in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2016 to January 2021 were retrospectively analyzed. Disease staging was defined according to the Chinese guidelines for diagnosis and treatment of MM (2020 edition). Risk stratification was based on the Mayo stratification of myeloma and risk-adapted therapy (mSMART) 3.0. The levels of Th1 and Th2 in peripheral blood of patients were detected by flow cytometry. Th1/Th2 was compared among patients with different disease staging and risk stratification. Using mSMART 3.0 risk stratification as the gold standard, the receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of Th1/Th2 for determining high-risk MM. According to the optimal cut-off value, patients were divided into high Th1/Th2 group (≥ optimal cut-off value) and low Th1/Th2 group (< optimal cut-off value). The progression-free survival (PFS) of the two groups was analyzed by Kaplan-Meier method. Multivariate Cox proportional hazards model was used to analyze the influencing factors of PFS.Results:There were 40, 62 and 66 patients with international staging system (ISS) stages Ⅰ, Ⅱ and Ⅲ, respectively, with Th1/Th2 [ M ( IQR)] of 19.20 (18.98), 15.93 (14.40) and 14.47 (12.01), respectively ( H = 6.68, P = 0.036). There were 31,102 and 35 patients with revised international staging system (R-ISS) stages Ⅰ, Ⅱ and Ⅲ, respectively, with Th1/Th2 of 19.67 (21.92), 14.87 (11.36) and 13.50 (12.80), respectively ( H = 7.26, P = 0.027). There were 99 and 69 patients with mSMART 3.0 high-risk and standard-risk, respectively, and the Th1/Th2 of high-risk patients was lower than that of the standard-risk patients [14.70 (11.93) vs. 17.72 (16.80), U = 2 612.00, P = 0.009]. ROC curve analysis showed that the area under the curve for Th1/Th2 to determine high-risk MM was 0.618 (95% CI 0.531-0.705, P = 0.010), and the optimal cut-off value was 16.55 and there were 81 and 87 cases in the high Th1/Th2 group and low Th1/Th2 group. With a median follow-up of 28 months (1-70 months), the median PFS time for all patients was 36 months (95% CI 29-43 months); PFS in high Th1/Th2 group was better than that in low Th1/Th2 group [median PFS time: 39 months (95% CI 26-51 months) vs. 28 months (95% CI 21-34 months), P = 0.040]. Multivariate Cox regression analysis showed that renal impairment (with vs. without: HR = 2.340, 95% CI 1.350-4.053, P = 0.002) and low Th1/Th2 (high vs. low: HR = 0.551, 95% CI 0.344-0.882, P = 0.013) were independent risk factors for PFS in MM patients. Conclusions:The imbalance between Th1 and Th2 is associated with the prognosis of MM patients, and patients with low Th1/Th2 are at high risk of progression. Th1/Th2 can be used as a prognostic indicator for MM.

Radioactivity level and risk assessment of thorium in surface water in Sichuan Province, China, 2016-2021 / 中国辐射卫生

Objective To investigate the content of thorium (Th) in surface water in Sichuan Province, China, and to evaluate Th-associated health risk via water intake for residents. Methods Twenty-three monitoring sections were set in main surface water bodies in Sichuan Province. From 2016 to 2021, the Th radioactivity level in the water bodies was measured during dry and normal-water seasons. The health risk of residents was evaluated by calculating radioactive Th intake from the surface water bodies combined with the use of a health risk assessment model. Results The Th radioactivity level of the surface water bodies in Sichuan Province was 0.02-0.67 μ./L. There was no significant difference in the Th radioactivity level of different years or different surface water bodies (P > 0.05). A significant difference was observed in the Th radioactivity level of different water seasons (P < 0.05). The total mean annual committed effective doses of Th in all age groups caused by drinking water and water immersion ranged from 3.14 × 10−8 to 8.75 × 10−7 Sv, all lower than the World Health Organization (WHO)-recommended reference level of 0.1 mSv. The overall carcinogenic risks for residents in all age groups ranged from 3.93 × 10−10 to 1.09 × 10−8, all below the most rigorous control limits issued by WHO and International Commission on Radiological Protection. Conclusion The Th-associated health risk via direct water intake and water immersion in main surface water bodies of Sichuan Province is at an acceptable level. Th in main surface water bodies of Sichuan Province is safe for all age groups.

Correlation of neutrophil extracellular traps with T cells differentiation in Hashimoto′s thyroiditis mice and vitamin D′s relief effect / 中华内分泌代谢杂志

Objective:To investigate correlation between neutrophil extracellular traps(NETs) formation and T cell subsets in mice with experimental autoimmune thyroiditis(EAT) and the impact of active vitamin D intervention.Methods:Six-week-old female BALB/c mice were randomly divided into Control group, EAT group and 1, 25 dihydroxy vitamin D 3[1, 25(OH) 2D 3] treatment group(VitD group; n=6/group). HE staining was used to observe thyroid pathology. Plasma thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and 1, 25(OH) 2D 3 were measured by ELISA. Peripheral NETs formation, Th1, Th2, and Th17 cell ratio from spleen were measured by flow cytometry. Correlation between NETs formation rate and Th1, Th2, and Th17 cell ratio was analyzed. Results:Compared with Control group, mice in EAT group had significantly increased thyroid inflammation scores, thyroiditis morbidity, TPOAb, TGAb levels, NETs formation rate, Th2(CD4 + IL-4 + or CD4 + IL-13 + )and Th17 cell proportions( P were <0.001, 0.002, 0.007, <0.001, <0.001, 0.003, 0.001, and 0.002, respectively), and significant decreased 1, 25(OH) 2D 3, Th1 cell proportions, Th1/Th2(CD4 + IL-4 + ), Th1/Th2(CD4 + IL-13 + ), and Th1/Th17 ratios( P were 0.010, 0.018, 0.010, 0.005, and 0.007, respectively). Compared with the EAT group, the VitD group had lower thyroid inflammation scores, TPOAb, TGAb levels, NETs formation rate, Th2(CD4 + IL-4 + or CD4 + IL-13 + ) and Th17 cell proportions( P were 0.044, 0.007, <0.001, 0.001, 0.014, 0.008, and 0.001, respectively), and significant higher Th1 cell ratio, Th1/Th2(CD4 + IL-13 + ) and Th1/Th17 ratio( P were 0.011, 0.009, and 0.003, respectively). The Th1/Th2(CD4 + IL-4 + ) was not significantly increased in VitD group compared with EAT group( P=0.174). NETs formation rate was positively correlated with Th2(CD4 + IL-4 + or CD4 + IL-13 + ) and Th17 cell proportion( r were 0.65, 0.59, and 0.61; and P were 0.004, 0.010, and 0.007, respectively), but not with Th1 cell proportion( r=-0.47, P=0.051). Conclusion:EAT mice were more prone to NETs formation. Active vitamin D may relieve immune imbalance with increased Th2 and Th17 cell ratio and decreased Th1 cell ratio by reducing the formation of NETs in EAT mice. Vitamin D played the protective role in thyroid by reducing thyroid pathological damage and thyroid autoantibody levels, and relived overall lymphocyte imbalance.

Spatial-temporal distribution of pulmonary tuberculosis registered in Fuling District of Chongqing during the 13th Five-Year Plan period / 中国热带医学

@#Abstract: Objective To analyze the spatial-temporal characteristics of the active pulmonary tuberculosis (PTB) and the pathogenic positive PTB in Fuling District of Chongqing during the 13th Five-Year Plan period, so as to explore the clustering areas, and provide scientific basis for the precise prevention and control of tuberculosis in Fuling District. Methods The PTB registration data of 27 townships in Fuling District from 2016 to 2020 were collected. The descriptive analysis were used to describe the temporal and spatial distribution characteristics of patients, SaTScan9.0 and ArcGis10.6 was used for spatial-temporal scanning analysis and local auto-correlation analysis. The results were visualized by ArcGis10.6. Results A total of 4 038 case of active PTB patients were registered and a downward trend was observed in PTB during the 13th Five-Year Plan period in Fuling District. The average annual registration rate of PTB was 70.17/100 000, and the annual PTB registration rate declined by 8.21%. The peak of active PTB and etiological positive PTB were mainly concentrated in March and June respectively. The top five streets of cumulative active PTB patients registered were Lizhi street, Dunren street, Chongyi street, Ma 'an street and Jiangdong street, accounting for 60.18% of the total registered PTB patients during the 13th Five-Year Plan period. The top three average annual registration rates were Dunren street (101.35/100 000), Chongyi street (101.34/100 000) and Wulingshan Township (99.21/100 000). The registered PTB from 2016 to 2020 showed a global auto-correlation (Moran's I=0.64, P<0.0001). The "high-high" area of active PTB and the etiological positive PTB all covered Lizhi street, Jiangdong street and Longqiao street. By scanning analysis of spatial-temporal, the primary cluster of active PTB concentrated in the main urban area south of the Yangtze River in Fuling during January 2016 to December 2017, and the primary cluster of pathogenic positive PTB concentrated in the main urban area south of the Yangtze River in Fuling and Jiangdong street during January 2019 to December 2020. Conclusions During the 13th Five-Year Plan period, there was the spatial-temporal clustering of PTB in Fuling District, which mainly gathered in the main urban area south of the Yangtze River in Fuling district and surrounding streets centered on Lizhi street.

Clinical efficacy of fire needling combined with cupping therapy on herpes zoster of acute stage and the effect on Th17/Treg cellular immune balance / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood.@*METHODS@#Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups.@*RESULTS@#From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group (P<0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group (P<0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group (P<0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group (P<0.05).@*CONCLUSION@#The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.

Influence of matrine on Th17/Treg balance in rats with inflammatory bowel disease by regulating IL-6/STAT3/NF-κB signaling pathway / 西安交通大学学报(医学版)

【Objective】 To investigate the influence of matrine (MT) on the balance of T helper cell 17 (Th17)/regulatory T cells (Treg) in rats with inflammatory bowel disease by regulating interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3)/nuclear transcription factor-κB (NF-κB) pathway. 【Methods】 SD rats were grouped into control check group (CK group), model group, low-dose MT group (MT-L group, 50 mg/kg), medium-dose MT group (MT-M group, 100 mg/kg), high-dose MT group (MT-H group, 200 mg/kg), mesalazine group (MSLM group, 0.42 g/kg), and MT-H+rIL-6 (IL-6 activator) group (200 mg/kg+0.05 mg/kg) according to the random number table method, with 18 in each group. Except for the CK group, the rats in other groups all received with 5% trinitrobenzenesulfonic acid (20 mg/kg) buffer solution mixed with 50% ethanol at a ratio of 1∶1 and then enema to construct a rat model of inflammatory bowel disease. After the successful modeling, they were treated with drug administration once a day for 7 weeks. The body weight of rats was measured at 1, 3, 5, and 7 weeks of administration; the changes of colon length of rats in each group were compared; HE staining was used to detect the pathological damage of rat colon tissue; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-17 and IL-10 in serum of rats were detected by ELISA; the proportions of Th17 and Treg cells in peripheral blood of rats were detected by flow cytometry; Western blottingt was performed to detect the protein expression of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein P3 (Foxp3), IL-6, p-STAT3, and p-NF-κB p65 in rat colon tissue. 【Results】 Compared with the CK group, the colon tissue of the model group was severely damaged by pathology, and the body weight (at 3, 5, and 7 weeks), the level of IL-10, the proportion of Treg cell, and the expression of Foxp3 protein were decreased, the colon length shortened, the levels of TNF-α, IL-17, the proportions of Th17 cell, Th17/Treg ratio, and the protein expression of RORγt, IL-6, p-STAT3, and p-NF-κB p65 increased (P<0.05). Compared with the model group, the corresponding indicators of the MT-L group, MT-M group, MT-H group, and MSLM group had the opposite trends (P<0.05); rIL-6 attenuated the promoting effect of high-dose MT on Th17/Treg balance in inflammatory bowel disease rats. 【Conclusion】 MT may promote Th17/Treg balance in inflammatory bowel disease rats by inhibiting IL-6/STAT3/NF-κB signaling pathway.