Objective To investigate the changes in plasma amyloid-β (Aβ) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aβ42 and Aβ40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aβ42,Aβ40,and Aβ42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aβ42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aβ42 level showed no significant difference among the three groups (P=0.227).The plasma Aβ40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aβ42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aβ42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aβ42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aβ42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aβ levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aβ levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.
Humans ; Diffusion Tensor Imaging ; White Matter/diagnostic imaging* ; Cognitive Dysfunction ; Outpatients ; Cognition ; Amyloid beta-Peptides

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E₂ and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E₂ levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
AMP-Activated Protein Kinases ; Animals ; Cyclin D2 ; Female ; Follicle Stimulating Hormone/therapeutic use* ; Humans ; Luteinizing Hormone/therapeutic use* ; Metformin/pharmacology* ; Mice ; Mice, Inbred C57BL ; Oogonial Stem Cells/metabolism* ; Ovarian Cysts/drug therapy* ; Ovarian Neoplasms ; Polycystic Ovary Syndrome/drug therapy* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; TOR Serine-Threonine Kinases

AIM: To evaluate the effect of 0.02% mitomycin-C(MMC)on the corneal density after transepithelial photorefractive keratectomy(Trans-PRK). METHODS: Retrospective case analysis. Selected 28 patients with 56 eyes in moderate myopia who underwent Trans-PRK surgery from January 2021 to June 2021 in our hospital. They were divided into MMC group in 28 eyes with a combination of 0.02% MMC 20s during the surgery and the control group in 28 eyes was not use MMC during the surgery. The Pentacam anterior segment analyzer was used to measured the corneal density in different diameter ranges and different thickness layers before and after surgery at 14d, and after surgery at 1 and 3mo.RESULTS: The total corneal density value of MMC group was 16.60(15.70,17.10 )before the surgery, after the surgery at 14d was 16.63(15.90,17.50 ), at 1mo was 16.57(15.10,16.70 ), at 3mo was 16.04(14.60,16.60 ). The total corneal density value of control group was 16.30(15.50,17.30 )before the surgery, after the surgery at 14d was 16.20(15.20,17.10 ), at 1mo was 16.08(14.90,16.40 )and at 3mo was 15.60(14.60,16.40 ). In the zone of 0-2mm diameter was centered on the corneal vertex, the corneal density of the two groups at 14d after the surgery was higher than those before surgery(P<0.001 ). In the zone of 2-6mm diameter, the corneal density of the two groups at 1mo and 3mo after surgery was higher than those before the surgery(P<0.001). In the zone of 6-10mm, the corneal density of the two groups at 14d, 1 and 3mo after surgery was higher than those before the surgery(P<0.001). In the layer of anterior 120 μm, the corneal density of the two groups at 1mo and 3mo after the surgery was decreased than that before surgery(P<0.01). In the middle layer, the corneal density of the two groups at 1mo after the surgery was decreased than those before surgery(P<0.01).CONCLUSION:The use of 0.02% MMC during the operation can reduce the corneal density and increase the corneal light transmittance in the early postoperative period. The occurrence and prognosis of haze can be effectively quantified by observing the changes of corneal optical density in different ranges in different time periods after operation.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

OBJECTIVES: This study aims to investigate the diagnostic value of peripheral blood circulating tumor cells (CTCs) in oral squamous cell carcinoma (OSCC) and its correlation with the clinicopathological features of OSCC. METHODS: Ninety-three patients diagnosed as OSCC in the First Affiliated Hospital of Zhengzhou University from May 2019 to May 2020 were selected as the experimental group, and 20 healthy volunteers were employed as the control group. The CTCs value of peripheral blood of the patients were measured by CTCs detection technology, and its clinical significance was analyzed. RESULTS: The CTCs values in the experimental group were higher than those in the control group, and the difference was statistically significant ( CONCLUSIONS Peripheral blood CTCs has important clinical value for early screening, auxiliary diagnosis, evaluation of metastasis, and determination of malignant degree, progression, and pathological grade of OSCC and a relatively reliable tumor detection indicator.
Carcinoma, Squamous Cell/diagnosis* ; Head and Neck Neoplasms ; Humans ; Mouth Neoplasms/diagnosis* ; Neoplastic Cells, Circulating ; Squamous Cell Carcinoma of Head and Neck

Objective To explore the association between mild cognitive impairment (MCI) and the risk of falls in community populations, so as to provide a reference for preventing falls in the elderly. Methods 826 community residents aged 55 years and older were enrolled in Wuzhong, Ningxia; cognitive function was assessed during the participants attending the basic public health examination, and self-report falling events were observed through telephone call survey after half a year. The incidence of falls among different populations was compared using unconditional Logistic regression model. Results A total of 521 participants completed the follow-up study, and 127 of them met criteria of MCI at baseline. 32 participants reported falling occurred during follow-up with a incidence of 6.1% (32/521), and the incidence of falls was higher (8.85%,23/260) in females than that of males (3.45%,9/261) (RR=2.56, P=0.010). The incidence among MCI group (9.45%,12/127) was 1.86 times of that among non-MCI group (RR=1.86, P=0.073). Under the controlling of demographic variables (gender, age and education level), there was no association between MCI and falls (RR=1.41, P=0.382). Conclusions The incidence of falls in the elderly communities is common, and females has higher risk of falls than males. There is no statistical association between MCI and risk of falls. Further validation is needed with large-sample studies in the future.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

BACKGROUND: As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis. METHODS: WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC). RESULTS: Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased. CONCLUSIONS IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.
Animals ; Chemokine CXCL1 ; metabolism ; Cytokines ; metabolism ; Disease Models, Animal ; Imiquimod ; toxicity ; Interleukin-17 ; metabolism ; Interleukin-18 ; metabolism ; Mice ; Mice, Knockout ; Psoriasis ; chemically induced ; genetics ; metabolism ; Skin ; immunology ; metabolism

Subjective cognitive decline(SCD),a clinical condition in the early stage of Alzheimer's disease,manifests as a continuous decrease in the individual's self-conscious cognitive function but with normal objective cognitive indicators. Research on SCD helps to identify individuals at high risk of senile dementia and explore the effective prevention and intervention strategies. This article reviews the recent research advances in SCD,with an attempt to provide evidence for early intervention in patients with SCD.
Alzheimer Disease ; Cognition ; Cognitive Dysfunction ; Humans