HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective To explore the differences in stress distribution and stability of the planta pedis in the patients with unilateral and bilateral plantar fasciitis(PF)through plantar stress and center of pressure(COP)analysis.Methods A total of 100 patients with PF visiting in this hospital were enrolled,among them 50 cases were unilateral heel pain(unilateral heel pain group)and 50 cases were bilateral heel pain(bilateral heel pain).Meanwhile,50 healthy subjects were included(healthy group).In the health group and bilateral heel pain groups,the average stress value of both planta pedis surfaces of each subject was taken and named as the J0 group and H2 group,respectively.In the unilateral heel pain group,the plantar stress in 50 healthy feet and 50 affected feet were named as the J1 group and H1 group,respectively.The plantar pedis was divided into 10 regions for analysis and comparison[the first foot toe(T1),T2-5,the first-fifth metatarsal bones(M1-M5),the mid foot(MF),heel medial side(MH),heel lateral side(LH)].The subjects in 3 groups conducted the static and dynamic tests respectively,and the differences in plantar stress distribution and COP parameters among the J1,H1,H2 and J0 groups were compared respectively.Results In the static tests,the maximum pressure of the LH regions in the group J1 was increased when compared with the group J0,the contact area of LH regions in the group H1 was reduced when compared with the group J0,the maximum pressure of the M2 and M3 regions in the H1 group was increased when compared with the group J0,the contact areas of the MH and LH regions in the H2 group were decreased when compared with the group J0,the maximum pressure of the M1 region was increased when compared with the group J0,and the differences were statistically significant(P<0.05).In the dynamic tests,the maximum pressure of the T2-5 regions in the J1 group was increased when compared with the J0 group,the maximum pressure of the M3 region in the group H1 was increased when compared with the group J0,the maximum pressure of the M3 and M4 region in the group H2 was in-creased when compared with the group J0,and the differences were statistically significant(P<0.05).The COP 95%confidence ellipse area in the health group was the smallest,followed by the bilateral heel pain group,and finally the unilateral heel pain group,and the differences among 3 groups were statistically signifi-cant(P<0.05),there was also statistically significant difference between pairwise comparisons in 3 groups(P<0.05).Conclusion In the static condition,the pressure of the healthy heel and affected forefoot in the patients with PF is increased;while in the dynamic condition,the pressure of the toes of the healthy foot and forefoot of the affected foot in the patients with PF is also increased.The distribution of plantar stress in the patients with PF has larger difference compared with the healthy population,and the stability is poor.Meas-ures can be taken to improve the abnormal force on the foot,reduce pain and reduce the risk of falling.

Objective:To investigate the correlation among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students.Methods:Seventy college students with mild depressive symp-toms who conformed to the standard of the Self-Rating Scale for Depression(SDS)of 53-62 and 70 normal col-lege students were recruited.The frontal alpha power was measured under quiet and closed-eye state,and the total physical activity(PA)was assessed with the International Physical Activity Questionnaire.Results:The college students with mild depressive symptoms had lower Total PA scores,right frontal alpha power and frontal alpha a-symmetry(FAA)than the normal controls(P＜0.001).In college students with mild depressive symptoms,the to-tal PA scores(r=-0.29,P＜0.05)and FAA(r=-0.41,P＜0.001)were negatively correlated with SDS scores,and the total PA scores were positively correlated with FAA(r=0.34,P＜0.01).Conclusion:The college students with mild depressive symptoms may have reduced physical activity and asymmetric right lateralization of frontal alpha power.There is a correlation among depressive symptoms,physical activity and frontal alpha power a-symmetry in college students with mild depressive symptoms.

Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related death worldwide, with anaplastic lymphoma kinase (ALK) fusion mutations accounting for approximately 4%-9% of cases. In recent years, there are increasing clinical evidences suggesting that the combination of ALK inhibitors with surgical treatment holds significant potential for clinical application in resectable early and locally advanced non-small cell lung cancer (NSCLC) patients. This review aims to summarize the advances in neoadjuvant targeted therapy for ALK fusion positive NSCLC and discuss its advantages and challenges in clinical practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Anaplastic Lymphoma Kinase/antagonists & inhibitors* ; Lung Neoplasms/enzymology* ; Neoadjuvant Therapy/methods* ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use*

The red gene is the crystallization of the ideas and wisdom of the Chinese Communist Party’s century-long struggle, and plays an irreplaceable and decisive role in cultivating socialist hospital culture and medical professionals in the new era. The Chinese Academy of Medical Science (CAMS) Cancer Hospital has a distinctive red gene trait. For more than 60 years since its establishment, through the protection of the red gene inheritance carrier, the enrichment of the content and expression form of the red gene inheritance, and the exploration and demonstration of the role model in the red gene inheritance, it has always integrated the red gene inheritance into the whole process of hospital construction, development and spiritual culture cultivation, and has achieved remarkable results, accumulated rich practical experience, and provided a useful reference for the spiritual and cultural construction of public hospitals.

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Objective:To understand the incidence of HIV infections and associated factors among men who have sex with men (MSM) in Jiangsu province.Methods:Based on national AIDS sentinel surveillance in 2019, MSM from 13 cities in Jiangsu were recruited for questionnaire interview and laboratory testing during April to July, 2019. Seropositive samples were tested with Limiting-antigen avidity enzyme immunoassay to detect recent HIV infections. The incidence of HIV infection in MSM were calculated according to the formula and parameters from China CDC. Multivariable logistic regression analysis was used to identify factors associated with recent infection of HIV.Results:A total of 4 469 MSM were subjects and the incidence of HIV infection were 4.5% (95% CI: 3.4%-5.5%).Multivariate logistic regression analysis results showed that compared with these aged ≥40 years, recruitment ways from MSM venues, awareness of AIDS knowledge, non-unprotected anal sex in the past 6 months and non-syphilis infection, those who aged 18-24 years (a OR=2.083,95% CI:1.087-3.990), recruitment ways from VCT clinics (a OR=2.125,95% CI:1.175-3.843), unawareness of AIDS knowledge (a OR=2.456,95% CI:1.109-5.437), unprotected anal sex in the past 6 months (a OR=3.553,95% CI:2.143-5.889) and syphilis infection (a OR=2.414,95% CI:1.033-5.462) were higher risk of HIV infection. Conclusion:The new infection rates of HIV were high in MSM in Jiangsu province. Health education, condom use and HIV/syphilis screening promotions should therefore be top priority in the prevention and control of HIV infection in MSM.

Objective:To evaluate the effect of clinic standardized blood pressure measurement model (SBPM) applying to first blood pressure measurement among community population aged 35 years old and above.Methods:SBPM was implemented in the community health service center of Dapuqiao street, Huangpu district of Shanghai from June 1, 2018, and the data between June 1 and December 31, 2018 was used as the SBPM data. The first-diagnosis blood pressure measurement data in this center between June 1 and December 31, 2017 was used as the conventional measurement (CM) model data. The detection rate of elevated blood pressure under SBPM was standardized according to the gender and age distribution of subjects in CM. The equilibrium of the value distribution of the end digit of blood pressure value in different pressure-measuring models and difference of elevated blood pressure rate of subjects with different characteristics and seasons were analyzed by using the χ 2 test, and the difference of standardized elevated blood pressure rate in different pressure-measuring models was analyzed by using the U test. Results:The SBPM included 1 548 subjects and 639 (41.28%) of them were males. The CM included 2 952 inpatients and 1 196 (40.51%) of them were males. The frequency of the end digit of blood pressure in SBPM ranged from 9.04% to 10.72%, and both systolic and diastolic blood pressure showed a balanced distribution of end digit ( P values were 0.996 and 0.981 respectively). The frequency of blood pressure end digital in the CM ranged from 0.37% to 67.92%, and both systolic and diastolic blood pressure showed an unbalanced distribution (both P values <0.001). The crude rate and standardized elevated blood pressure rate in SBPM were 23.19% (359/1 548) and 23.05%, which were higher than that in CM, about 7.22% (213/2 952) (both P values <0.001). The elevated blood pressure rate in SBPM in summer, autumn and winter was 18.85% (141/748), 26.72% (152/591) and 31.58% (66/209), respectively, which was higher than that in CM, about 6.28% (91/1 450), 7.20% (82/1 139) and 11.02% (40/363), respectively (all P values <0.001). Conclusion:The quality of blood pressure data and the efficiency of hypertension screening of SBPM are better than those of CM when applying to first blood pressure measurement among community population aged 35 years old and above.

Objective:To evaluate the effect of clinic standardized blood pressure measurement model (SBPM) applying to first blood pressure measurement among community population aged 35 years old and above.Methods:SBPM was implemented in the community health service center of Dapuqiao street, Huangpu district of Shanghai from June 1, 2018, and the data between June 1 and December 31, 2018 was used as the SBPM data. The first-diagnosis blood pressure measurement data in this center between June 1 and December 31, 2017 was used as the conventional measurement (CM) model data. The detection rate of elevated blood pressure under SBPM was standardized according to the gender and age distribution of subjects in CM. The equilibrium of the value distribution of the end digit of blood pressure value in different pressure-measuring models and difference of elevated blood pressure rate of subjects with different characteristics and seasons were analyzed by using the χ 2 test, and the difference of standardized elevated blood pressure rate in different pressure-measuring models was analyzed by using the U test. Results:The SBPM included 1 548 subjects and 639 (41.28%) of them were males. The CM included 2 952 inpatients and 1 196 (40.51%) of them were males. The frequency of the end digit of blood pressure in SBPM ranged from 9.04% to 10.72%, and both systolic and diastolic blood pressure showed a balanced distribution of end digit ( P values were 0.996 and 0.981 respectively). The frequency of blood pressure end digital in the CM ranged from 0.37% to 67.92%, and both systolic and diastolic blood pressure showed an unbalanced distribution (both P values <0.001). The crude rate and standardized elevated blood pressure rate in SBPM were 23.19% (359/1 548) and 23.05%, which were higher than that in CM, about 7.22% (213/2 952) (both P values <0.001). The elevated blood pressure rate in SBPM in summer, autumn and winter was 18.85% (141/748), 26.72% (152/591) and 31.58% (66/209), respectively, which was higher than that in CM, about 6.28% (91/1 450), 7.20% (82/1 139) and 11.02% (40/363), respectively (all P values <0.001). Conclusion:The quality of blood pressure data and the efficiency of hypertension screening of SBPM are better than those of CM when applying to first blood pressure measurement among community population aged 35 years old and above.

Objective A lentivirus-mediated colon cancer cell line stably overexpressing human SAMHD1 gene was constructed to observe the effect of this gene on the ability of the cells to resist herpes simplex virus type 1 (HSV-1) infection. Methods p CDH-EF1-MCS-SAMHD1-T2 A-GFP recombinant plasmid was constructed using pCDH-EF1-MCS-T2 A-copGFP lentiviral vector. After confirming successful synthesis with sequencing, the recombinant plasmid and lentivirus packaging plasmids were co-transfected into 293 T cells. The pseudovirus solution was collected and concentrated, then human colon cancer cells were infected with the concentrated solution. The cell line overexpressing SAMHD1 gene was infected with HSV-1 in contrast to the control group, and the virus infection efficiency was assessed by Western blotting and immunofluorescence analyses. Results The pCDH-EF1-MCS-SAMHD1-T2 A-GFP recombinant plasmid was successfully constructed and verified by gene sequencing. Western blotting confirmed the overexpression of the SAMHD1 gene with higher levels of the gene in the transfected cells in contrast to control human colon cancer cell line. Western blotting and immunofluorescence showed that the cell line overexpressing human SAMHD1 gene could effectively inhibit the infection of HSV-1. Conclusion Lentivirus-mediated stable cell line overexpressing human SAMHD1 gene was effective in inhibiting HSV-1 replication and could help us to further investigate the function of SAMHD1.