Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To investigate the role of dendritic cells (DC) in Chlamydia muridarum ( Cm) respiratory infection and their effect on adaptive immune response. Methods:C57BL/6 mice were exposed to 1×10 3 inclusion-forming units (IFU) of Cm through inhalation to establish the mouse model of Cm respiratory infection. The proportion of CD11c + MHCⅡ + DC and the expression of costimulatory molecules (CD40, CD80 and CD86) in spleen tissues were detected by flow cytometry on 0, 3 and 7 d after infection. The expression of IL-12p40, IL-10 and IL-6 at mRNA level in spleen tissues was detected by qPCR. Mouse splenic DC isolated on 7 d after Cm infection were sorted by magnetic beads and then transferred to recipient mice. Th1 response in the recipient mice was measured using intracellular cytokine staining 14 d after infection. Results:Cm respiratory infection induced massive infiltration of DC and promoted the expression of costimulatory molecules on splenic DC. The expression of IL-12 and IL-10 at mRNA level in splenic DC reached the peak on 3 d after infection. Transferring the splenic DC of Cm-infected mice into the recipient mice could alleviate the disease condition in the recipient mice after Cm infection with reduced Cm inclusion-forming units in lung tissues and significantly increased proportion of Th1 cells in lung and spleen tissues. Conclusions:Cm respiratory infection could induce the maturation and activation of DC, which promoted Th1 immune response. DC played an important role in Cm infection.

Objective:To explore the effect of family supportive nursing on self-perception and outcome events in elderly patients with chronic diseases.Methods:A simple random sampling method was used to select 115 elderly patients with chronic diseases discharged from Henan Provincial People's Hospital from January 2019 to January 2020. They were divided into the observation group (58 cases) and the control group (57 cases) by random number table method. The control group received routine nursing, while the observation group received family support nursing. The self-perception and family function scores of the two groups were compared before the intervention and after 3 and 6 months of the intervention. The medication compliance and readmission rate were compared between the two groups.Results:After 3 months of intervention, scores of Self-Perceived Burden (SPBS) of the observation group and the control group were respectively (25.73±3.85) and (28.14±3.90) and scores of Family Adaptability Cohesion Environment Scale (FACES) were respectively (105.62±12.41) and (96.35±10.05) . After 6 months of intervention, the SPBS scores of the observation group and the control group were respectively (21.89±4.33) and (25.41±4.20) , and the FACES scores were (122.60±14.70) and (112.35±16.32) respectively. Repeated-measures analysis of variance showed that there were statistically significant differences in interaction effect, time effect and between-group effect in the comparison of SPBS and FACES total scores between the two groups (all P<0.01) . After 6 months of intervention, the rate of good medication compliance in the observation group and the control group was respectively 70.69% (41/58) and 50.88% (29/57) , and that of the observation group was higher than the control group, and the difference was statistically significant (χ 2=4.738, P=0.030) . After one-year follow-up after intervention, the readmission rates of the observation group and the control group were respectively 18.87% (10/53) and 39.22% (20/51) , and the observation group was lower than the control group, and the difference was statistically significant (χ 2=5.243, P=0.022) . Conclusions:Family support nursing can reduce the self-perceived burden of elderly patients with chronic diseases, improve their family function, improve medication compliance and reduce readmission.

Objective:To investigate the effects of Chlamydia muridarum ( Cm) respiratory tract infection on the infiltration and polarization of alveolar macrophages (AMs) and pulmonary interstitial macrophages (IMs). Methods:A C57BL/6 mouse model of Cm respiratory tract infection was established through nasal inhalation. Flow cytometry was used to detect AMs (CD45 + F4/80 + CD11c + ) and IMs (CD45 + F4/80 + CD11c -) in lung tissues at 0, 3, 7 and 14 d after Cm respiratory tract infection. The proportions of M1 (CD80 + , CD86 + , MHCⅡ + , iNOS + ) and M2 (CD206 + , Arg1 + ) macrophages in AMs and IMs were also detected. Results:(1) Cm respiratory tract infection induced the infiltration of AMs and IMs. Compared with the uninfected group (0 d), the proportions and the numbers of AMs and IMs of were significantly increased 3 d after infection ( P<0.05, P<0.01). The numbers of AMs and IMs reached the peak 7 d after infection ( P<0.001). (2) Compared with the uninfected group, the proportions of CD80 + and CD86 + cells in AMs were significantly up-regulated 3 d after infection ( P<0.05, P<0.01); the proportion of MHCⅡ + cells in AMs increased after infection and reached the peak at 14 d ( P<0.05), while the proportion of CD206 + cells decreased after infection ( P<0.05). (3) Compared with the uninfected group, the proportions of CD80 + and CD86 + cells in IMs were increased 3 d after infection ( P<0.05, P<0.001) and the proportion of MHCⅡ + cells was significantly increased 14 d after infection ( P<0.01), while there was no significant change in the proportion of CD206 + cells. (4) In AMs, the proportion of iNOS + cells increased continuously after infection ( P<0.01), while the proportion of Arg1 + cells decreased continuously after infection, especially at 7 d and 14 d ( P<0.05). In IMs, the proportion of iNOS + cells reached the peak at 7 d ( P<0.001), but the proportion of Arg1 + cells showed no significant change after infection. Conclusions:Cm respiratory tract infection induced the infiltration of AMs and IMs, stimulated the polarization of AMs and IMs towards the M1 phenotype and weakened the polarization of AMs to M2 macrophages, but had no significant influence on the polarization of IMs towards the M2 phenotype.

Objective:To investigate the public psychosocial status and regional differences of Chinese residents during the outbreak of the novel coronavirus pneumonia epidemic.Methods:A convenience sampling method was used to distribute online self-assessment tools of mental health including the Self-Reporting Questionnaire (SRQ-20), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) through WeChat and other self media platforms from January 30 to February 13, 2020. A total of 14 592 people from all over the country were evaluated on mental health. The positive detection rate was regarded as the primary outcome measure.Results:The positive detection rate of SRQ-20 was 33.2% (4 840/14 592), and that of the PHQ-9 was 53.5% (7 503/14 037), with 29.3% (4 115/14 037) for mild, 14.0% (1 967/14 037) for moderate and 10.1% (1 421/14 037) for severe depression. The positive detection rate of GAD-7 was 44.6% (6 196/13 904), with 27.8% (3 862/13 904) for mild, 10.2% (1 413/13 904) for moderate and 6.6% (921/13 904) for severe anxiety. Except for a few areas, the positive rates of these three scales were almost the same all over the country, and the anxiety level of the inhabitants in Hubei province (GAD-7:54.7%) was significantly higher than that in other provinces ( P<0.05). Conclusion:As a Public Health Emergency of International COVID-19 has brought obvious psychological impact to the nationwide people, with more prominent in anxiety and depression. The public is in a general group crisis in the early stage of the outbreak, especially in areas with serious epidemic situation. It is suggested that great attention should be paid to public mental health while fighting against the epidemic situation aiming at ensuring their life safety, so as to implement effective psychological assistance and timely psychological crisis intervention.

Objective:To investigate the public psychosocial status and regional differences of Chinese residents during the outbreak of the novel coronavirus pneumonia epidemic.Methods:A convenience sampling method was used to distribute online self-assessment tools of mental health including the Self-Reporting Questionnaire (SRQ-20), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) through WeChat and other self media platforms from January 30 to February 13, 2020. A total of 14 592 people from all over the country were evaluated on mental health. The positive detection rate was regarded as the primary outcome measure.Results:The positive detection rate of SRQ-20 was 33.2% (4 840/14 592), and that of the PHQ-9 was 53.5% (7 503/14 037), with 29.3% (4 115/14 037) for mild, 14.0% (1 967/14 037) for moderate and 10.1% (1 421/14 037) for severe depression. The positive detection rate of GAD-7 was 44.6% (6 196/13 904), with 27.8% (3 862/13 904) for mild, 10.2% (1 413/13 904) for moderate and 6.6% (921/13 904) for severe anxiety. Except for a few areas, the positive rates of these three scales were almost the same all over the country, and the anxiety level of the inhabitants in Hubei province (GAD-7:54.7%) was significantly higher than that in other provinces ( P<0.05). Conclusion:As a Public Health Emergency of International COVID-19 has brought obvious psychological impact to the nationwide people, with more prominent in anxiety and depression. The public is in a general group crisis in the early stage of the outbreak, especially in areas with serious epidemic situation. It is suggested that great attention should be paid to public mental health while fighting against the epidemic situation aiming at ensuring their life safety, so as to implement effective psychological assistance and timely psychological crisis intervention.

Objective To investigate the relationship between various loop electrosurgical excision procedure (LEEP) margin status and residual high grade squamous intraepithelial lesion (HSIL) or worse at hysterectomy following conization. Methods The relevant clinicopathological data were collected in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2014 to Dec. 2015, including 947 cases who underwent hysterectomy within 6 months of LEEP. The residual HSIL or worse at hysterectomy were analyzed among the groups. (1) Clear margins, involved margins, and without 1 mm negative margins. (2) Only one positive margin, two positive margins and three positive margins. (3) A positive margin of internal ostium of cervix, of external ostium of cervix and of the basement. Results (1) The histological evaluation of the uterine specimens showed residual HSIL or worse in 234 cases (24.7％, 234/947). The proportion of residual lesions was 7.3％ (21/286) in population with clear margins, 33.2％ (211/635) with involved margins, 7.7％ (2/26) without 1 mm negative margins, respectively. The positive margins group had significant difference at the aspect of residual rate in contrast to the negative margins group and the without 1 mm negative margins group (P<0.01). Further studies conclusively showed that the proportion of residual lesions was very similar between the negative margins group and the without 1 mm negative margins group (P>0.05). (2) The involved margins were interpretable in 621 cases. This was detected in 25.3％(111/438) patients with only one positive margin, 47.4％(74/156) with two positive margins and 77.8％(21/27) among three positive margins, respectively (P<0.01). (3) Furthermore, there were 418 cases only one positive margin was definite, and the proportion of residual lesions was 31.0％(62/200) in population with a positive margin of internal ostium of cervix, 18.2％(31/170) of external ostium of cervix and 33.3％(16/48) of the basement. The residual rates were higher in the endocervical and basal margin groups than that in the ectocervical margin group, and the differences were significant (P<0.05). Conclusions The risk of residual HSIL or worse is significantly greater with involved margins at hysterectomy following LEEP. Both the positive endocervical and basal margin are excellent predictors of residual diseases, while the without 1 mm negative margin may be not. Clinicians should avoid treating it as positive margin and prevent overtreatment.

Objective: To investigate the clinical and pathological characteristics and prognosis of ovarian clear cell borderline tumor. Methods: A total of 12 cases of ovarian clear cell borderline tumors recorded were collected from May 2011 to December 2017 at Obstetrics and Gynecology Hospital, Fudan University.Clinical histories were retrieved and pathological slides were reviewed. Results: The age of the patients ranged from 35 to 65 years with a mean age of 52 years. Seven cases were associated with cystic endometriosis of the ovary. All tumors consisted of irregular and crowded glands or cysts embedded in a fibromatous stroma. The cysts and glands were lined by mild to moderate atypical cells.CK7 and HNF-1β were expressed in all cases, and Naspin A was expressed in 11 cases. ARID1A expression was absent in 5 cases and p53 showed wild-type expression. None of the cases developed recurrence during follow-up ranging from 7 to 79 months. Conclusions Ovarian clear cell borderline tumor may be associated with endometriosis and tumor suppressor gene ARIDA. The tumor has a good prognosis without recurrence and progression to carcinoma.

Objective:To investigate the clinical and pathological characteristics of ovarian cellular fibromas.Methods:The sample con-sisted of 24 cases of ovarian cellular fibromas from February 2008 to March 2017 in the Obstetrics and Gynecology Hospital of Fudan University.Clinical histories were retrieved,and pathological slides were reviewed.Results:The age of the patients ranged from 17 to 70 years old,with a mean age of 46.5 years.Clinical symptoms included ovarian masses,abdominal pain,or pleuroperitoneal fluid.Se-rum CA125 notably increased in two patients.Of the 24 cases,13 and 10 occurred in the right and left ovaries,respectively,and one case occurred bilaterally.Tumor cells were densely cellular in all cases and were mitotically active in three cases(5-7/10 high power fields).A minor component of sex cord elements(<10% area of the tumor)was present in three cases,and luteinized cells were ob-served in four cases.None of the cases manifested recurrence during follow-up ranging from 1 month to 109 months.Conclusion:Ovarian cellular fibromas are pure ovarian stromal tumors that may manifest mitotic activity, sex cord elements, and luteinization. Some patients present with pleuroperitoneal fluid and increased CA125.Thus,the pathological features of cellular fibromas must be mastered to avoid misdiagnosis for other benign or malignant tumors and improper treatment.

Objective To evaluate the diagnostic value of six-slice coronal reformations in patients with acute midepigastric pain. Methods A total of 974 patients with acute midepigastric pain were included in this study and divided into group A(coronal reformation)and group B(non-coronal reformation).For group A,reconstructed coronal and oblique-coronal images were acquired.A comprehensive diagnosis was made based on coronal reformations and axial planes.Anatomical nomenclature was adopted,including kidney-ureter plane,abdominal aorta plane,superior mesenteric artery plane,ascending colon-appendix plane,stomach-cholecyst plane and colon-small intestine plane.For group B,the diagnosis was made based on axial planes.Finally,a comprehensive analysis was made,missed cases in these two groups were counted and compared,and statistical analysis was performed using the SPSS software(version SPSS V17).Results For group A,the missed diagnosis was made in 12 cases(1.23%)and it was 53 cases(6.58%)for group B.There was a statistically significant difference between two groups(P<0.05).Conclusion Combined with axial planes or oblique coronal reformations,six-sclice coronal reformation can reduce the the rate of missed diagnosis of acute midepigastric pain.