Volume 99 ·  Issue 03 ·  2019

In the past 10 years, progress has been made in targeted research and treatment of key immune links such as B cells, T cells and cytokines in patients with systemic lupus erythematosus (SLE). Some therapeutic drugs have been used clinically, and many drugs have entered the clinical research stage., the era of biological targeted therapy for SLE has arrived. This article mainly reviews the clinical research hotspots, core and prospect of biological targeted therapy for SLE.

To investigate the role of T follicular helper (Tfh) subsets and T follicular helper effector memory (Tfhem) cells in circulation of patients with systemic lupus erythematosus (SLE), and explore their roles in SLE disease activity index as biomarkers.

This study enrolled 64 patients with SLE and 15 healthy controls. In peripheral blood from patients with SLE and health controls, the percentage of Tfhem (CD3⁺CD4⁺CD45RA^-CXCR5⁺CCR7^lowPD-1^high) cells, Tfh (CD3⁺CD4⁺CD127^highCD25^low CD45RA^-CXCR5⁺) subset: Tfh1 (CXCR3⁺CCR6^-Tfh), Tfh2 (CXCR3^-CCR6⁺ Tfh), Tfh17 (CXCR3^-CCR6⁺ Tfh), were detected by flow cytometry. The correlations of Tfhem/Tfh subsets with clinical indicators which we collected were analyzed.

The percentage of Tfhem was significantly increased in SLE patients compare to health controls (1.40±1.12 vs 0.51±0.24, P<0.000 1), and it was also correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P=0.015 3) and anti-dsDNA antibody (P=0.003 1), but not with complement C3 (C3), complement C4 (C4), erythrocyte sedimentation rate (ESR), and C reaction protein (CRP). In addition, the percentage of Tfh2, but not Tfh1 or Tfh17, was significantly increased in SLE patients compare to health controls (3.83±2.74 vs 2.18±1.07, P=0.000 4). As compared to anti-dsDNA antibody<25 group, the percentage of Tfh2 in anti-dsDNA antibody>25 group was increased with no significant statistical difference (4.33±3.20 vs 3.70±1.070,P=0.069 6).

Our investigation show that Tfhem is associated with SLEDAI and it is a valuable evaluation biomarker for disease process and treatment. Meanwhile Tfhem is also associated with anti-dsDNA antibody, and it plays an important role in autoantibody production in SLE pathogenesis. Tfhem may be a good therapeutic target in SLE. For the meantime, the percentage of Tfh2 is significantly increased in SLE patients, and it had certain correlation with anti-dsDNA antibody, it might be involved in the development of SLE.

To explore the function and role of innate lymphoid cells in the pathogenesis of systemic lupus erythematosus (SLE) at different disease activity levels.

From Nov 2017 to May 2018, 40 patients with SLE and 15 age-matched healthy non-immune-related diseases controls were enrolled from Anhui provincial hospital. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, the patients were divided into active group (n=20) and remission group (n=20). The frequency of ILCs, B cells, CD4+T and CD8+T cells from peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. The subsets of ILCs in each group were compared with the subsets of B cells and T cell respectively. The levels of IL-4, IL-33 and IFN-γ in each group were tested by ELISA.

Compared with the control group, ILC1 percentage was significantly increased in SLE active group [(22.33%±2.52%) vs (14.56%±1.28%), P=0.018 1]; ILC2 percentage was decreased significantly in both remission group [(19.67%±1.83%) vs (42.48%±3.46%), P<0.000 1] and active group [(8.67%±0.83%) vs (19.67%±1.83%), P<0.000 1]; ILC3 percentage was decreased significantly in active group [(5.72%±1.08%) vs (14.35%±2.40%), P=0.001 3]. SLEDAI score was negatively correlated with the percentage of ILC2 (P=0.023 9) in all patients. The percentage of ILCs in the remission group (P=0.046 2) and activity group (P=0.003 7) were both increased significantly. Moreover, the percentage of ILC2 in active group was negatively correlated with CD4+T cells (P=0.030 8), and the serum IgG was negatively correlated with ILC2% in all patients (P=0.013 8). Compared with control group or remission group, the levels of IFN-γ (F=10.91, P=0.000 1) and IL-4 (F=6.046, P=0.004 7) in active group were remarkable higher. However, IL-33 was significantly reduced in active group (F=6.645, P=0.002 7). The percentage of ILC2 (r=0.154 3, P=0.028 8) and ILC3 (r=0.313 6, P=0.001 1) in all patients with SLE were positively correlated with the level of IL-4.

The percentage of ILCs is related to disease activity, and ILCs play a "double-edged" role in the pathogenesis of SLE. Its function and mechanism are worth further exploration.

Serum anti Müllerian hormone (AMH) was used to evaluate the effect of cyclophosphamide (CTX) on ovarian function in female patients with systemic lupus erythematosus (SLE).

A total of 121 female patients who were 18-50 years old with normal menstruation were selected. Among them, 54 patients were treated with CTX as the study group and the remaining 67 cases as the control group. Before and after treatment for 6 months, the clinical characteristics, menstruation and AMH level of all patients were recorded and detected. At the same time, the method of using CTX and the cumulative measurement are recorded.

(1) Before treatment, there was no significant difference in AMH and mean age, duration of disease and SLEDAI score between the CTX treatment group and the control group. The renal injury in the CTX treatment group (44.4%) was higher than that of the control group (34.3%), and the difference was statistically significant (P<0.05). (2) After 6 months of treatment, the AMH of group CTX decreased from (2.39±1.58) μg/L to (1.56±1.42) μg/L, and the difference was statistically significant ( P<0.01). But there was no significant change in the control group. In 54 cases of CTX treatment group, 23 cases (42.6%) had different degree of menstrual abnormalities, while 67 cases had only 8 cases (11.9%) in the control group. Moreover, the AMH level of 31 cases with abnormal menstruation was (0.95±0.59) μg/L, which was significantly lower than that of the other 90 normal cases (2.36±1.58) μg/L. (3) In 54 cases of CTX treatment group, the cumulative dose of CTX was less than 3 g in 14 cases, 33 cases of 3-6 g, 7 cases greater than 6 g. AMH was all were lower than those before treatment. But there was a statistical difference between the 3 g group and 3-6 g group before treatment, and there were statistical differences between the groups.

CTX can damage ovarian function in women of childbearing age SLE. Low dose intravenous CTX may have less damage. Serum AMH can be used to monitor ovarian function in patients with SLE and to guide individualized treatment.

To analyze the 20-year survival rate, causes of death and predictors of systemic lupus erythematosus (SLE).

A retrospective analysis was performed on 217 newly SLE patients who were diagnosed and treated by Peking University People′s Hospital before June 2008. The clinical features and serologic data were studied. Survival rate of SLE patients over time, living conditions, causes of death and prognostic indicators of mortality were studied.

The 10-, 15-and 20-year cumulative survival rate was 90.3%,88.1%and 79.6%, respectively. Infection and lupus encephalopathy were the main causes of death. Cox regression analysis revealed that lupus nephritis, neuropsychiatric systemic lupus erythematosus and age at the diagnosis were independent risk determinants for mortality.

Prognosis of SLE remains to be improved. Early diagnosis, control of SLE organ damage and infection prevention are critical to improve survival of SLE patients.

To evaluate the long term change of the cervical sagittal profile in adolescent Chiari malformation type Ⅰ (CMI)/syringomyelia undergoing posterior fossa decompression (PFD) and to further evaluate the correlation between the syrinx resolution and cervical sagittal profile.

A retrospective radiographic study was performed in 32 adolescents undergoing PFD for CMI/syringomyelia from October 2011 to August 2015 with a minimum 2-year follow-up. There were 23 males and 9 females, with a mean age of (13.7±2.8) years (range, 10-16 years). The following parameters including upper cervical angle (C₀-C₂), lower cervical angle (C₂-C₇), sagittal balance (C₂-C₇SVA), cervical curvature index (CCI), syrinx size and length were compared preoperatively and at the last follow-up. The correlation of syrinx resolution and cervical sagittal parameters were further analyzed with Pearson correlation analysis.

All patients received a followed-up for 2.0-6.5 years [mean (3.9±1.1) years]. The lower cervical angle and CCI were-29.8°±11.4° and 29.1%±7.1% at the last follow-up, respectively, which were significantly higher than those before surgery (-15.2°±8.8°, 13.4%±4.2%)(t=2.917, 2.902, both P<0.05). The syrinx size and length were also obviously decreased at the last follow-up. No significant difference was found in the upper cervical angle and C₂-C₇SVA before operation and at the last follow-up (t=0.302, 0.871, both P>0.05). There were significantly positive correlations between the differences of syrinx width and the lower cervical angle, and the CCI before and after surgery (r=0.611, 0.652, both P<0.05). Significantly positive correlations were also observed between the differences of syrinx length and the lower cervical angle, and the CCI before and after surgery (r=0.504, 0.514, both P<0.05).

The cervical lordosis can be restored after PFD in adolescents with CMI/syringomyelia. The resolution of syrinx may play an important role in restoring the cervical sagittal alignment.

To investigate the short-term effect of Isobar dynamic stabilization system fixation combined with lumbar discectomy in patients with lumbar disc herniation.

From June 2015 to June 2017, 62 patients with lumbar disc herniation treated in the First Affiliated Hospital of Zhengzhou University were divided into control group and observation group according to the therapy. The 31 patients in the control group were treated with simple excision of nucleus pulposus and the 31 patients in the observation group were treated with Isobar dynamic stabilization system fixation combined with lumbar discectomy. The score of Oswestry disability index (ODI) and Japanese Orthopedic Association (JOA) score of low back pain, lumbar and adjacent stage activity, inflammatory factor levels[C reaction protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α)] were compared between the two groups before and after the operation and 6 months after the operation. The data were compared between the two groups with t test.

After the operation and 6 months after, the ODI scores of the two groups decreased and the JOA scores increased significantly (25.5±3.0, 27.5±3.2 vs 15.3±2.2 and 18.6±2.3, 23.3±2.9 vs 15.3±2.0), the ODI scores of the observation group was significantly lower than those in the control group; the JOA scores were significantly higher than those in the control group (t=0.04-10.19, all P<0.05). The operative time, hospital stay, intraoperative blood lose and complications rate in the observation group were all significantly lower than those in the control group. The total activity of lumbar vertebrae in the observation group was significantly higher than that in the control group after operation and 6 months after (t=37.67, 36.60, both P<0.05); the activity of adjacent segments in the observation group was significantly lower than that of the control group (t=9.28, 3.79, both P<0.05); the Pfirrmann grade was significantly lower than that in the control group (t=3.11, 5.05, both P<0.05). The levels of CRP, IL-6 and TNF-α in the two groups were lower than those before operation, and those were also significantly lower in the observation than the corresponding indexes in the control group (t=0.52-10.99, all P<0.05).

Isobar dynamic stable system fixation combined with lumbar intervertebral disc resection can effectively improve the lumbar function and lumbar activity in patients with lumbar intervertebral disc herniation, and reduce the level of inflammation and relapse.

To analyze the relationships between cerebral blood perfusion and impairments of cognitive function in patients with Alzheimer′s disease (AD) and mild cognitive impairment (MCI).

A total of 21 patients with AD, 18 patients with MCI and 21 healthy adults as control group (NC group) matched in age, gender and education were recruited between November 2016 and November 2017 from Northern Jiangsu People′s Hospital. All cases were performed routine head MRI, arterial spin labeling (ASL). Cognitive function evaluation including simple mental state scale (MMSE) and improved Addenbrooke′s cognitive examination revised (ACE-R) of patients were also assessed. The difference between cerebral blood perfusion signals and cognitive impairment of the three groups were analyzed.

The subtest scores of attention and orientation, memory, language fluency, language and visual space of ACE-R scores were significantly reduced (P<0.001,uncorrected) for AD when compared with MCI. Using REST1.8 software to perform single factor ANOVA, and adjusted for P<0.05. The AD group showed a decrease in total cerebral perfusion compared to the NC group, a decrease and in the frontotemporal lobe compared to MCI group; compared with the normal group, MCI group also showed decreased perfusion in frontotemporal cortex. Pearson correlation analysis was performed on the cerebral blood flow and ACE-R scores in the AD group and the MCI group,the decrease degree of CBF in multiple brain regions was positively correlated with the total score of ACE-R′s total scores, and the subtest score of ACE-R including attention and orientation, memory, language fluency, language and visual space also showed positive correlation.

ASL technology can detect the changes of cerebral blood flow metabolism in AD and MCI patients, and reveal association relationships between brain function damage and cerebral blood flow metabolism in AD and MCI patients.

To explore the application value of adaptive statistical iterative reconstruction (ASIR) combined with low tube voltage in three-stage enhanced low-dose scan of liver.

From March 2017 to November 2017, two groups which each group included 50 patients were randomly selected at the Second Affiliated Hospital of Harbin Medical University with different stages of arterial phase, delayed phase and portal vein scanning. GE Discovery CT 750 HD Liver CT Ⅲ was used during enhanced scanning. A total of 100 patients included 56 males and 44 females, aged 27-73 years old and 42 patients with hepatocellular carcinoma, 44 patients with hepatic hemangioma, and 14 patients with other diseases. The arterial and delayed period of group A patients were scanned with a low dose of 100 kV+ASIR, and the portal vein phase was conventional. Dosage scanning was 120 kV+FPP; the arterial and delayed period of group B was normal dose scanning, 120 kV+FPP, and the portal vein phase was low dose scanning, 100 kV+ASIR. At the same time, FBP reconstruction was used for all low-dose scanning phases to obtain low-dose images under normal reconstruction mode. The objective evaluation index of image quality was analyzed by completely randomized design analysis of variance, and Dunnett-t test was used to compare the two groups. For the subjective evaluation part, the rank sum test of multiple groups was used.

ASIR combined with low tube voltage enhanced low dose scanning in the third phase of the liver, and the radiation dose decreased by 37% in the low dose group compared with the normal dose group. There was no statistically significant difference between the low dose group (100 kV+ASIR) and the normal dose group (120 kV+FPP) in subjective image quality evaluation (P>0.05); objective evaluation of image quality except for low dose(100 kV+ASIR) portal stage noise slightly worse than conventional dose group (120 kV+FBP) (low dose 10.86±1.98, conventional dose 9.40±2.12, P<0.05), the other indexes in each period were superior or indifferent to the normal dose group.

ASIR technique combined with low tube voltage can be used in the third phase of liver enhanced low-dose scanning and the image quality is improved.

To explore the value of CT and autoantibody panel to diagnosis the subtype in early clinical stage lung cancer,especially lepidic predominant adenocarcinoma (LPA),and to provide the correct information for the clinical and the prognosis evaluation.

A retrospective study was conducted of 60 patients (total 63 subsolid nodules,which included 39 PSN and 24 pGGN) who underwent surgical resection or needle biopsy for stage Ⅰa or Ⅰb lung adenocarcinoma at Affiliated Tumor Hospital of Zhengzhou University between June 2017 and April 2018,age from 28 to 82 years old,and the average age was (52±7) years. All patients underwent a pretreatment chest LDCT and the peripheral blood of all patients were used to detect the tumor related antibody (including p53, GAGE7, PGP9.5, CAGE, MAGEA1, SOX2, GBU4-5) through enzyme linked immunosorbent assay. All the patients were divided into LPA group (43 subsolid nodules, which included AIS 10 subsolid nodules, MIA 11 subsolid nodules, LPA 22 subsolid nodules) and invasive predominant adenocarcinoma (IPA) group (20 subsolid nodules). The information of CT scanning was measured and assessed in lung and mediastinal windows with double blind method. The mean computed tomography (m-CT) value and the solid component/tumor ratio in three-dimensional (3D) and two-dimensional (2D) planes were measured and analyzed using computer-aided diagnosis (CAD) system.

There were 20 partial solid nodules in IPA group, 19 partial solid nodules in LPA group and 24 ground-glass nodules (χ²=19.278,P=0.000). There were 4 circular nodules, 16 irregular nodules in the IPA group, 21 circular nodules, 5 oval nodules and 7 irregular nodules in the LPA group χ ²=8.587,P=0.003). The incidence of burr, vascular aggregation and bronchial truncation in IPA group was higher than that in LPA group (40.0% vs 16.3%, 70.0% vs 18.6%, 30.0% vs 2.3%, χ ²=4.234,15.860,10.580, P=0.040,0.000, 0.001). The incidence of clear tumor lung interface in patients in LPA group was significantly higher than that in patients in IPA group (97.7% vs 65.0%, χ ²=13.146,P=0.00). Of all the quantitative analysis of nodules,the m-CT value, the solid component/tumor ratios in three-dimensional (3D) and two-dimensional (2D) planes in IPA group were higher than those of LPA group ((-180±156) vs (-410±213) HU, 0.44±0.32 vs 0.14±0.26, 0.54±0.26 vs 0.18±0.26, t=-4.208, -3.951、-5.166, P=0.000, 0.000, 0.000). Among the 60 patients with lung cancer, there were 33 cases with positive antibody in peripheral blood, with a positive rate of 55.0%. The positive rate of 7-AABs was 70.0% in IPA group and 44.2% in LPA group, which had no statistical difference (χ²=3.647, P=0.056), the positive expression of tumor-associated antibodies was independent of the patient′s age, CT value and nodular solid components and lung nodular volume ratio and area ratio, P>0.05, only in correlation with pleural traction (χ²=3.866, P=0.049).

Compared with IPA, the imaging features of LDCT about the mGGN and PGGN appearance, clear tumor-lung interface, low m-CT and the solid component/tumor ratio in two-dimensional or three-dimensional (3D) planes are benefit for the diagnosis of the LPA; the expression of tumor-associated antibody group is independent of the age of the patient and the number of nodular solid components, and is only related to pleural depression, which is not conducive to the identification of LPA and IPA.

To evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) and digital subtraction angiography (DSA) for renal artery stenosis (RAS).

Fifty-seven hypertensive patients suspected for RAS admitted in Beijing Hospital from September 2017 to August 2018 were enrolled. All 114 renal arteries were assessed by CEUS and DSA. RAS was subdivided into low-(30%-50%), moderate-(50%-69%) and high-grade (70%-99%) subgroups. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were compared between CEUS and DSA results.

Fifty-seven hypertensive patients (31 males, mean age 57.1 years) involving 114 renal arteries were included. Overall, DSA identified RAS in 71(62.3%) renal arteries, mild RAS, 34(29.8%); moderate RAS, 23(20.2%); severe RAS, 14(12.3%). With CEUS, the sensitivity, specificity, accuracy, PPV and NPV for detecting mild-grade RAS were 85.3%, 97.3%, 91.5%, 96.7% and 87.8%; for detecting moderate-grade RAS were 82.6%, 97.9%, 92.9%, 95.0% and 92.2%; for detecting high-grade RAS were 85.7%, 98.2%, 95.8%, 92.3% and 96.5%. The measure of agreement kappa was 0.92 between CEUS and DSA.

CEUS is a safe and accurate method for the diagnosis and severity classification of RAS, especially those with kidney injury.

To investigate whether the cell deformation induced by RhoA/ROCK signaling pathway plays a regulatory role in the osteogenic differentiation in human mesenchymal stem cells (hMSCs).

The primary hMSCs were cultured until the P3 generation was added to the osteogenic induction solution for 14 days, and the expression levels of RhoA and ROCK-1 proteins were detected by immunofluorescence. Another P3 generation hMSCs cells were divided into induction group, blank plus drug group and medicated group, and the induction group was induced by simple osteogenic induction; the blank drug-added group was added to the osteogenic induction solution and the solvent dimethyl sulfoxide (DMSO) for induction culture; the medicinal group was added with osteogenic induction solution and Y-27632 (RhoA/ROCK signaling pathway inhibitor) dissolved in DMSO for induction culture. The proliferation of the cells was detected by CCK-8 methods. The changes of cytoskeleton in each group were observed by fluorescence microscope. The expression changes of osteogenic genes alkaline phosphatase (ALP), osteocalcin (OCN) and runt-relatedtranscriptionfactor-2 (RUNX-2) in each group were detected by real time polymerase chain reaction (RT-PCR) and ALP staining. The t test was used for data comparison between the two groups.

There were significant differences in the expression of RhoA and ROCK-1 protein before and after osteogenic induction of hMSCs (22.7±2.1 vs 14.7±0.6 and 24.3±1.5 vs 20.3±0.6, t=-6.414, -4.243, both P<0.05). Mesenchymal stem cell proliferation on day 1, 5, 9 and day 14 in the medicated group were comparable with those in the induction group (F=0.427, 1.000, 0.298, 1.314, all P>0.05). The cytoskeleton of the medicated group showed obvious spindle-shaped changes, and the cell spreading area became smaller. From the three groups of ALP staining on the 14th day, it can be seen that the color of the medicated group was significantly lighter than that of the induction group. The results of RT-PCR showed that the expression of osteogenic phenotypic genes increased with the induction time in the induction group and the blank drug-treated group, the expression levels of osteogenic phenotype genes ALP, OCN and RUNX-2 in the drug-treated group were gradually decreased with the induction time. The expression of ALP in the drug-treated group was significantly lower than those in the other two groups at 14th day (F=25.891, P=0.001); the expression of OCN in the drug-treated group was significantly lower than those in the other two groups at 11th and 14th days (F=5.773, 25.382, both P<0.05); the expression of RUNX-2 in the drug group was significantly lower than those in the other two groups at 11th and 14th days (F=34.972,10.808, both P<0.05).

The RhoA/ROCK signaling pathway may play a role in promoting osteogenic differentiation of hMSCs through mediating cytoskeletal deformation.

To investigate the effect of Baicalin on the expression of connexin 36 (Cx36) in cerebral cortex and striatum area of 6-OHDA-induced Parkinson′s (PD) model rats and its significance.

Male Sprague-Dawley (SD) rats were randomly divided into 6 groups, 12 in each group: normal control group, PD model group (untreated group), PD model (Medopa group), PD model (Baicalin low dose group) PD model (Baicalin medium dose group) and PD model (Baicalin high dose group). Except for the normal control group, 6-OHDA was injected using microinjection under the mouse brain stereotaxic apparatus to establish the hemiparkinsonian PD model. On the basis of the success of making model, the rats were treated by Medopa and Baicalin (low, medium and high dose). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) and Cx36 expression in cerebral cortex and striatum of the 6 groups. Western-Blot technique was used to detect the cerebral cortex and striatum Cx36 expression changes, and to preliminarily study the effect of Baicalin on rat cerebral cortex and striatum Cx36 expression levels.

Immunohistochemical staining and Western blotting showed that the expression of TH-positive neurons and Cx36 in the cerebral cortex and striatum of the PD model group was lower than that of the normal control group (828±188). While expressions of Cx36 in the low, medium and high dose PD model groups of Baicalin (733±118, 759±134, 779±125) were up-regulated, compared with the untreated PD model group (487±125), and the differences were statistically significant (all P<0.05), but the difference between the doses was not statistically significant (P>0.05).

The expression of Cx36 decreases in cerebral cortex and striatum area of 6-OHDA-induced Parkinson′s disease model rats, and the expressions of TH and Cx36 in cerebral cortex and striatum increase after treatment with Baicalin, which may provide new drug research direction for Parkinson′s disease.

In this study, the expression of sphingosine phosphate receptor 2 (S1P2) in the hippocampus of rats was observed by immunohistochemistry, Western blot and immunofluorescence staining in a rat model of temporal lobe epilepsy induced by pilocarpine. It was found that the expression of S1P2 in the hippocampus of epileptic rats decreased significantly in the acute and chronic phases, and the expression of S1P2 in the hippocampal astrocytes of epileptic rats. S1P2 may be involved in the formation of temporal lobe epilepsy by affecting neuronal function and astrocytic proliferation.

A 74-year-old male patient was admitted due to a mass in the left upper abdomen with abdominal distension and abdominal pain after eating for 20 d. The abdominal magnetic resonance left lateral lobe of the liver occupies huge mass, and the diagnosis is as follows: (1) The left lateral lobe of the liver occupies huge mass, considering hemangioma; (2) Multiple lymphadenopathy in retroperitoneum, consider lymphoma. Left lateral lobectomy + retroperitoneal lymph node biopsy were performed. Pathological diagnosis: (1) Cavernous hemangioma (left outer lobe of liver); (2) Diffuse large B-cell lymphoma (left lateral lobe of liver, retroperitoneal lymph node).

Granulomatous mastitis is a refractory chronic inflammatory disease of the breast, among which the cases caused by taking antipsychotic drugs are relatively rare clinically. This patient is a 23-year-old female, unmarried and unchildless, with clinical manifestations of left breast redness, swelling and pain. She had been taking olanzapine for a long time due to schizophrenia in the past. The patient's serum prolactin level was significantly increased, and she was diagnosed with antipsychotic drug-related granulomatous mastitis. After specialist evaluation, the dosage of olanzapine was reduced, and the patient's condition improved after external application of traditional Chinese medicine Jinhuang Powder and surgical incision and drainage + sore clearance.

A 20-year-old woman with a family history of generalized verrucous xanthoma of the mouth, vulva and skin is reported. After orthopedic resection of vulvar hyperplasia, medial femoral lesion CO₂After laser therapy, the dermatology department gave acitretin capsules for oral administration, 0.03% tacrolimus ointment and adapalene gel for topical use, the condition improved.

Post-stroke depression (PSD) is one of the common complications of stroke, and there are different opinions about its risk factors. In this paper, the main risk factors of PSD were summarized from the bio-psychological-social medical model, and the possible molecular mechanisms were analyzed through the neurohumoral-immune regulation level, so as to improve the prognosis of stroke patients and increase everyone's attention to and prevention of PSD risk factors.

Osteoarthritis is a multi-factor disease, and its pathogenesis is cartilage matrix degradation, synovial inflammation, chondrocyte apoptosis and autophagy. miRNAs are a type of non-coding RNA that can play a role in the formation and development of osteoarthritis through inflammation, cartilage matrix degradation, apoptosis, autophagy, etc., and some miRNAs can be used as novel biomarkers of osteoarthritis, and some even have the potential to become therapeutic targets for osteoarthritis.

Narcolepsy is easily misdiagnosed as schizophrenia with the main clinical symptoms of uncontrollable excessive daytime drowsiness, paroxysmal cataplexy, sleep paralysis, hallucinations before falling asleep and sleep disorders at night. Narcolepsy combined with schizophrenia can also be seen clinically. It is a special subgroup with schizophrenia-like symptoms, including the comorbidity of primary narcolepsy and schizophrenia or the adverse reactions of long-term central nervous system stimulants. Its etiological mechanism has not been clarified. Because of its complexity, it is often missed or misdiagnosed clinically. The diagnosis of schizophrenia is based on clinical evaluation. Sleep monitoring and blood HLA DQB1*0602 gene detection are helpful for the diagnosis of narcolepsy, and cerebrospinal fluid detection of Hcrt-1/Orexin-1 level can confirm the diagnosis. In terms of treatment, the medication of the two diseases is contradictory, and the advantages and disadvantages need to be weighed.