Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Genotype-Phenotype Correlation Analysis of WT1 Gene Variants in Denys-Drash Syndrome and Frasier Syndrome / 罕见病研究

ObjectiveThis study aims to explore the association between different genotypes of WT1 gene variations and the phenotypes of Denys-Drash syndrome (DDS) and Frasier syndrome (FS).MethodsThrough searching and summarizing the case information of WT1 gene variations recorded in NCBI PubMed and CNKI databases from January 1, 1991 to October 31, 2023, we analyzed the association between variation types, occurrence locations, and phenotypes such as progressive renal function impairment, genitourinary developmental abnormalities, nephroblastoma, and gonadal tumors between DDS and FS.ResultsA total of 128 articles, including 304 subjects, were included in this study, and 86 pathogenic variations of the WT1 gene were detected.The distribution characteristics of these variations were as follows: the most common occurrence was in exon 9(24/86, 27.9%) and exon 8 (23/86, 26.7%); the most common variation type was missense mutation(51/86, 59.3%), followed by splice site mutation (13/86, 15.1%).The disease types caused by WT1 gene variations were as follows: DDS had the highest number of cases (174/304, 57.2%), followed by FS (83/304, 27.3%); DDS was mainly caused by missense mutations on exon 9 and exon 8 (143/174, 82.2%), while FS was mainly caused by splice site mutations on intron 9 (76/83, 91.6%).ConclusionsThe missense variants in exon 9 and exon 8 on the WT1 gene mainly resulted in DDS, while the splice variants in intron 9 mainly resulted in FS. Infants and children with progressive renal injury should undergo a comprehensive evaluation of the genitourinary system, and early genetic diagnosis should be established to improve prognosis.

Application status of risk assessment models for periodontal disease / 口腔疾病防治

@#Risk assessment models for periodontal disease provide dentists with a precise and consolidated evaluation of the prognosis of periodontitis, enabling the formulation of personalized treatment plans. Periodontal risk assessment systems have been widely applied in clinical practice and research. The application fields of periodontal risk assessment systems vary based on the distinctions between clinical periodontal parameters and risk factors. The assessment models listed below are commonly used in clinical practice, including the periodontal risk calculator (PRC), which is an individual-based periodontal risk assessment tool that collects both periodontal and systemic information for prediction; the periodontal assessment tool (PAT), which allows for quantitative differentiation of stages of periodontal disease; the periodontal risk assessment (PRA) and modified periodontal risk assessment (mPRA), which are easy to use; and the classification and regression trees (CART), which assess the periodontal prognosis based on a single affected tooth. Additionally, there are orthodontic-periodontal combined risk assessment systems and implant periapical risk assessment systems tailored for patients needing multidisciplinary treatment. This review focuses on the current application status of periodontal risk assessment systems.

Study on quality control method of the roots and rhizoma of Toricellia angulata / 中国药房

OBJECTIVE To establish the quality control method for the roots and rhizoma of Toricellia angulata. METHODS The properties of the roots and rhizoma of T. angulata were observed and microscopic identification was conducted. The moisture， total ash， acid-insoluble ash and ethanol-soluble extract were examined according to the method stated in the 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata were established， common peaks were identified and the similarity was evaluated by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）. The contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol were determined by HPLC. RESULTS The properties and microscopic identification of the roots and rhizoma of T. angulata were obvious. The average contents of moisture， total ash， acid-insoluble ash and ethanol-soluble extract were 7.54%， 2.18%， 0.15% and 7.81%， respectively. There were 16 common peaks marked in the HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata， with similarities of 0.856-0.960； five of them were identified， such as coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol. The contents of the above five components were 0.047 2-0.401 6， 0.836 8-8.697 9， 1.245 3-10.950 0， 0.139 0-0.437 8 and 0.016 4-0.635 3 mg/g， respectively. CONCLUSIONS The established method is stable and accurate， which can be used for the quality control of the roots and rhizoma of T. angulata. It is preliminarily proposed that the moisture in the roots and rhizoma of T. angulata is not more than 11.0%， the total ash is not more than 4.0%， the ethanol-soluble extract is not less than 5.0%， the contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D- glucopyranoside and syringaresinol are not less than 0.04，0.83， 1.24， 0.13， 0.01 mg/g， respectively.

Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia / 中国药房

OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients， and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th， 2021 to Jun. 30th， 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software， and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard， the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study， among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia， with an incidence of 6.41%. After the false positive patients were excluded， 473 patients were included finally， including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR＝1.043， 95%CI （1.017， 1.070）]， estimated glomerular filtration rate （eGFR） [OR＝0.988，95%CI（0.977， 0.998）]， baseline platelet （PLT） [OR＝0.989， 95%CI（0.982， 0.996）]， nutritional risk [OR＝3.863， 95%CI（1.884， 7.921）] and cumulative defined daily doses （DDDs） [OR＝1.082， 95%CI（1.020， 1.147）] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia （P＜0.05）. The C-index values of the training set and the internal validation set were 0.824 [95%CI （0.759， 0.890）] and 0.828 [95%CI （0.749， 0.933）]， respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 （P＝0.802） and 1.804 （P＝0.406）. In the external validation set， the C-index value was 0.808 [95%CI （0.672， 0.945）]， the χ 2 value of the Hosmer-Lemeshow test was 0.899 （P＝0.638）. CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age， baseline PLT， eGFR， nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability， which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.

Comparison of intravitreal injection of Ranibizumab versus Conbercept in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Viral pathogen spectrum analysis of acute intestinal infection in Hanzhong in 2019-2022 / 公共卫生与预防医学

Objective To explore the viral pathogen spectrum characteristics of acute intestinal infection in Hanzhong from 2019 to 2022. Methods Fecal samples from patients with acute intestinal infection in the outpatient clinic of 3201 Hospital from January 2019 to December 2022 were collected. Common enteroviruses such as enterovirus 71 (EV-A71), coxsackievirus 16 (CV-A16), CV-A10, CV-A6, CV-A2, CV-A4, and CV-B3 were detected and analyzed by real-time fluorescence quantitative PCR. Results A total of 5 194 fecal samples were collected, and the positive rate of nucleic acid detection was 23.95%. In terms of the enteroviruses, the highest detection rate was 9.82% for EV-A71, followed by 4.58% for CV-A16 and 3.37% for CV-A6. The positive detection rate of common enteroviruses showed statistical difference among different age groups (P0.05). EV-A71 infection showed no seasonal characteristics, whereas the detection of CV-A16 and CV-A6 infections was concentrated in summer and autumn. There were 106 cases of mixed infection, and the prevalence rate was 2.04%, with EV-A71 and CV-A6 mixed infections accounting for the majority of cases. Conclusion The main pathogens of acute intestinal infections in the Hanzhong area from 2019 to 2022 are EV-A71, CV-A16, and CV-A6. It is necessary to strengthen the monitoring of acute intestinal infections in children aged 4 years and below.

Ethical Thoughts on the Quality Evaluation of the Kidneys from Expanded Criteria Donors / 中国医学伦理学

In the case of extremely shortage of donor kidney sources, the number of Expanded Criteria Donors (ECD) with relatively poor kidney quality and transplantation effect is increasing. In order to alleviate the contradiction between supply and demand by using transplantable kidneys as much as possible and avoid the failure or poor effect of transplantation caused by poor quality kidneys, the quality assessment and evaluation criteria of ECD kidney have become a research hotspot in the field of kidney transplantation. This paper analyzed the possible ethical defects in the research process, and put forward some suggestions for the transplantation team to strictly follow the ethical principles of "no harm", "beneficial" and "informed consent", and the organ transplantation ethics committee to pay attention to the ethical review of the quality evaluation process of ECD donor kidney.

Discussion on the legal attributes of provincial Chinese herbal pieces processing norms / 中国药房

OBJECTIVE To provide a reference for the definition of the legal attributes of the provincial Chinese herbal pieces processing norms and the improvement of legal expression for the drug standards in Drug Administration Law. METHODS Based on the legal evolution of local drug standards in China， the composition of national drug standards for Chinese herbal pieces and the composition of current provincial Chinese herbal pieces processing norms were analyzed； at the same time， based on the method of legal interpretation， the legal connotation of the provincial Chinese herbal medicine processing norms in Drug Administration Law was investigated. RESULTS & CONCLUSIONS In the practice of drug supervision， the provincial Chinese herbal pieces processing norms are essentially local drug standards. The newly revised Drug Administration Law defines the drug standards specifically， but does not stipulate the legal attribute of drug standards for the provincial Chinese herbal pieces processing norms， and there are certain legislative technical defects. It is suggested that when amending the Drug Administration Law， the legal attributes of the drug standards of the provincial Chinese herbal medicine processing norms should be clarified.

A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys / 神经科学通报·英文版

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

The effects of drainage tube on pain and functional recovery after unicompartmental knee arthroplasty / Efeitos do tubo de drenagem na dor e recuperação funcional após artroplastia unicompartimental do joelho

ABSTRACT Objective: The objective of this study was to evaluate the impact of drainage tube placement on postoperative pain, recovery, and opioid consumption within a 72-hour period following unicompartmental knee arthroplasty (UKA). Methods: Patients with medial knee osteoarthritis who underwent UKA from January 2019 to August 2020 were enrolled in the study and divided into two groups based on whether they received a drain postoperatively. Results: The drainage group had significantly lower VAS scores on day 1, day 2, and day 3, in addition to significantly smaller changes in the circumference of the knee joint within 3 days postoperatively (P <0.05). The ROM in the drainage group significantly increased at 3 days and 1 month post-surgery, with a statistically significant difference in morphine consumption between the two groups at 3 days (P<0.05). The incidence of postoperative nausea and vomiting (5 cases) and wound bleeding (1 case) was lower in the drainage group compared to the non-drainage group (P<0.05). Conclusions: The placement of a drainage tube in UKA may reduce the swelling of knee joint and pain, which not only reduces the use of Opioid but also facilitates early functional activities of the knee joint. Level of Evidence III; Retrospective Comparative Study.

RESUMO Objetivo: O objetivo deste estudo foi avaliar o impacto da implantação do tubo de drenagem na dor pós-operatória, na recuperação e no consumo de opioides em um período de 72 horas após a artroplastia unicompartimental do joelho (UKA). Métodos: Pacientes com osteoartrite medial do joelho submetidos à UKA de janeiro de 2019 a agosto de 2020 foram incluídos no estudo e divididos em dois grupos com base no fato de terem ou não recebido um dreno no pós-operatório. Resultados: O grupo de drenagem apresentou escores EVA significativamente menores no dia 1, no dia 2 e no dia 3, além de alterações significativamente menores na circunferência da articulação do joelho em 3 dias de pós-operatório (P <0,05). A ADM no grupo de drenagem aumentou significativamente em 3 dias e 1 mês após a cirurgia, com uma diferença estatisticamente significativa no consumo de morfina entre os dois grupos em 3 dias (P<0,05). A incidência de náuseas e vômitos no pós-operatório(5 casos) e sangramento da ferida (1 caso) foi menor no grupo de drenagem em comparação com o grupo sem drenagem (P<0,05). Conclusão: A utilização de tubo de drenagem na UKA pode reduzir o edema articular do joelho e a dor, reduzindo o uso de opioides e facilitando as atividades funcionais iniciais da articulação do joelho. Nível de Evidência III; Estudo Comparativo Retrospectivo.

Preliminary application of foldable pedicled latissimus dorsi myocutaneous flap for repairing soft tissue defects in shoulder and back / 中国修复重建外科杂志

OBJECTIVE@#To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back.@*METHODS@#Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage.@*RESULTS@#All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site.@*CONCLUSION@#The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.

Remyelination Regulated by microRNAs in Neurodegenerative Diseases： A Review / 中国实验方剂学杂志

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Lactic Acid Inhibits the Cytotoxicity of NK-92 Cells via Activating the Lactate Receptor GPR81

Aims: Lactate acid functions as not only an energy source but a signaling molecule through the lactate receptor GPR81 under physiological conditions. However, the pathological role of lactic acid in the tumor microenvironment remains unclear, particularly for immune cells. Methodology: NK-92 cells were treated with L-lactic acid solutions at final concentrations of 10, 20, 30, and 40 mM, and its cell viability and cytotoxicity on A549 cells and A375 cells were evaluated by CCK8 assay and crystal violet assay, respectively. Furthermore, qPCR was used to assess the expression of GPR81 and cytotoxicity-related genes in NK-92 cells treated with antagonist and agonist. And their relationship between lactate/GPR81 pathway and cytotoxicity-related genes were analyzed by Pearson’s correlation. Results: The viability of NK-92 cells was inhibited by L-lactic acid with increasing concentration. Additionally, the cytotoxic activity against tumor cells of NK-92 cells treated with L-lactic acid decreased with increasing concentration. Moreover, qPCR results demonstrated that GPR81 can be activated by lactic acid or agonist (3,5-DHBA) and downregulate the expression cytotoxicity-related genes which included FASLG gene(Fas Ligand),TNF-? gene(Tumor necrosis factor-?), INFG gene (Interferon-?), RPF1 gene (Perforin 1), GZMA gene (Granzyme A), GZMB gene (Granzyme B), GZMH gene (Granzyme H), GAMK gene (Granzyme K) and GZMM gene (Granzyme M). And the expression of GPR81 returned to near-control level when treated with L-lactic acid in the presence of antagonist (3-OBA), the expression of cytotoxicity-related genes did as well. Pearson’s correlation analysis of cytotoxicity-related genes with GPR81 revealed that their correlation coefficient seems negative. Conclusion: Lactic acid can activate the GPR81 to downregulate the expression of cytotoxicity-related genes, subsequently lower the cytotoxicity of NK-92 cells.

Treatment of Menopausal Syndrome Based on Phlegm，Stagnation，and Fire / 中医杂志

Menopausal syndromes are mostly based on kidney deficiency， which could be expalined that kidney governing essence storage and controlling innateness， so when the kidney water was deficient and the liver fail to nourish， then led to liver depression and transform into fire； deficiency of the kidney， loss of warmth of the spleen， and inability to transport and transform the water and dampness will easily lead to phlegm and fire； the decline of the kidney yin and loss of water and fire will easily cause the exuberance of heart fire. Therefore， clinical symptoms of hot flashes， insomnia， and palpitations are common due to phlegm， depressions， and fire. Based on this， at the beginning of the treatment， we should treat the symptoms firstly by resolving phlegm， relieving depression and clearing fire， and commonly use Huanglian Wendan Decoction （黄连温胆汤）， Yigan Powder （抑肝散）， Chaihu plus Longgu Muli Decoction （柴胡加龙骨牡蛎汤）， and Qingxin Zishen Decoction （清心滋肾饮）， etc. After improving the symptoms of hot flashes and sweating， irritability， dreaming and frightening， then we should give the prescriptions to tonify kidney yang and nourish kidney yin， in order to eliminate the pathogens and reinforce healthy qi， and to treat both the manifestations and the root cause， so that the symptoms of the patients can be better alleviated.

Risk factors and prediction model of perioperative esophagogastric anastomotic leakage after esophageal cancer surgery / 中国胸心血管外科临床杂志

@#Objective    To analyze the risk factors for esophagogastric anastomotic leakage (EGAL) after esophageal cancer surgery, and to establish a risk prediction model for early prevention and treatment. Methods    Clinical data of patients undergoing esophagectomy in our hospital from January 2013 to October 2020 were retrospectively analyzed. The independent risk factors for postoperative EGAL were analyzed by univariate and multivariate logistic regression analyses, and a clinical nomogram prediction model was established. According to whether EGAL occurred after operation, the patients were divided into an anastomotic fistula group and a non-anastomotic fistula group. Results    A total of 303 patiens were enrolled, including 267 males and 36 females with a mean age of 62.30±7.36 years. The incidence rate of postoperative EGAL was 15.2% (46/303). The multivariate logistic regression analysis showed that high blood pressure, chronic bronchitis, peptic ulcer, operation way, the number of lymph node dissected, anastomotic way, the number of intraoperative chest drainage tube, tumor location, no-supplementing albumin in the first three days after operation, postoperative pulmonary infection, postoperative use of bronchoscope were the independent risk factors for EGAL after esophageal cancer surgery (P<0.05). A prognostic nomogram model was established based on these factors with the area under the receiver operating characteristic curve of 0.954 (95%CI 0.924-0.975), indicating a high predictive  value. Conclusion    The clinical prediction model based on 11 perioperative risk factors in the study has a good evaluation efficacy and can promote the early detection, diagnosis and treatment of EGAL.

Association between dietary quality and perceived stress based on the CHNS database / 公共卫生与预防医学

Objective To explore the association between dietary quality and perceived stress among adult Chinese. Methods The China Health and Nutrition Survey (CHNS) was used to investigate the association between dietary quality and perceived stress in Chinese adults. The Chinese Perceived Stress Scale (CPSS) was used to assess the perceived stress in Chinese adults. Binary logistic regression models were utilized to explore the relationship between diet quality and perceived stress. Restricted cubic splines (RCS) were utilized to clarify the dose response relationship between diet quality and perceived stress. Results Binary logistic regression models revealed that adults with CHEI score ranged from P25 to P50 and higher than P75 had 15.1% (OR=0.849，95%CI：0.738-0.977) and 23.0% (OR=0.770，95%CI：0.666-0.891) reduced risk of high perceived stress after multivariable adjustment when compared with adults with CHEI score less than P25. RCS results showed that the OR value of high perceived stress risk decreased gradually with increasing CHEI score in the overall population, but this association was not statistically significant in adults with lower CHEI score. Conclusion High dietary quality is associated with a reduced risk of high perceived stress. This study provides a theoretical reference for the health effects of high dietary quality on high perceived stress risk reduction.

Dilemma and optimization strategies of school psychological crisis intervention from multiple perspectives / 中国学校卫生

Objective@#To understand the dilemma of different participants in school psychological crisis intervention, so as to provide guidance for the implementation of comprehensive psychological crisis intervention from multiple perspectives.@*Methods@#From March 2022 to January 2023, a total of 10 psychological consultants, 10 counselors, 10 peer students, 10 parents and 10 clients were selected from a certain university using convenient sampling method was interviewed with semi structured interviews, and the transcribed data were analyzed according to grounded theory.@*Results@#The predicaments of psychological crisis intervention mainly involved three core themes: early warning, ethical dilemma and negative emotion. Early warning approaches mainly included three core themes: school, social media and other institutions, and 50 participants reported mainly on peer students in schools(18 cases) and online media in social media(18 cases). Ethical dilemmas mainly focued on the conflict between confidentiality breaches and privacy protection. The negative emotions mainly include three core themes of anxiety, fear and powerlessness, which were characterized by dispersion. The optimization expectation of psychological crisis intervention mainly consisted of two core themes: professional expectation and collaborative expectation, both of which were the common expectation of the people involved.@*Conclusion@#School psychological crisis intervention should pay attention to the establishment of crisis early warning system and dialectic between confidentiality breaches and privacy protection. Schools should prevent the dispersion of negative emotions of participants, deepen professional construction and the coordination between home and school, and implement psychological crisis intervention from a comprehensive perspective.

Expression of p21-activated kinase 2 in laryngeal squamous cell carcinoma and its correlation with clinicopathological characteristics and chemosensitivity / 肿瘤研究与临床

Objective:To investigate the expression of p21-activated kinase 2 (PAK2) in laryngeal squamous cell carcinoma and its relationship with the clinicopathological characteristics and chemosensitivity of patients.Methods:Transcriptome sequencing (RNA-seq) data for laryngeal squamous cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) database, and 123 patients were included in the study (12 cases had cancer tissues and normal tissues data, and the remaining 111 only had cancer tissues data). Differential expression of PAK2 in cancer and para-cancer tissues was analyzed by using R software, and the potential function of PAK2 in laryngeal squamous cell carcinoma was investigated by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database signaling pathway enrichment. A total of 34 patients with primary laryngeal squamous cell carcinoma tissues and corresponding para-carcinoma 34 tissue specimens who underwent surgical resection were retrospectively selected from Chaoyang Central Hospital between April 2016 and June 2021, and 20 cases of normal laryngeal mucosa tissues were selected as the controls. Immunohistochemistry was used to detect the expression of PAK2 in various tissues, and its correlation with clinicopathological factors was analyzed. A total of 35 supraglottic primary laryngeal squamous cell carcinoma patients were retrospectively collected before induction chemotherapy during the same period, including 20 patients sensitive to chemotherapy and 15 patients resistant to chemotherapy. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of PAK2 mRNA in cancer tissues.Results:Analysis of TCGA database data showed that PAK2 expression was increased in cancer tissues compared with that in para-cancer tissues ( P = 0.012); KEGG database signaling pathways showed that the high expression of PAK2 in laryngeal squamous cell carcinoma was related to signal transduction pathways, cell cycle, and cancer. Immunohistochemistry showed that the proportion of PAK2 positive in 34 cases of laryngeal squamous cell carcinoma tissues was higher than that in adjacent tissues and normal tissues [58.82% (20/34) vs. 0.03% (1/34), 0 (0/20), all P < 0.001]. There were statistically significant differences in the proportion of PAK2 positive patients stratified with different degrees of differentiation [high differentiation vs. low or middle differentiation: 33.33% (6/18)vs. 87.50% (14/16)], lymph node metastasis [presence vs. absence: 90.91% (10/11) vs. 43.48% (10/23)], TNM staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 82.35% (14/17) vs. 35.29% (6/17)] (all P < 0.05), and PAK2 positive patients were not associated with clinical type, tumor size, smoking history, drinking history, and age (all P > 0.05). qRT-PCR showed that the relative expression level of PAK2 mRNA in the chemotherapy-resistant group was higher than that in the chemotherapy-sensitive group (3.89±0.12 vs. 0.78±0.23, P < 0.001). Conclusions:The expression level of PAK2 in laryngeal squamous cell carcinoma tissues is increased, and the high expression of PAK2 is closely related to the malignant clinical characteristics of patients with laryngeal squamous cell carcinoma. The high expression of PAK2 may indicate the insensitivity to traditional chemotherapy regimens, and PAK2 may be a potential gene that targets and regulates the chemosensitivity of laryngeal squamous cell carcinoma.