Objective:To evaluate the cost-effectiveness of hepatitis C screening in general population in China, and find the age group in which hepatitis C screening can achieve the best cost-effectiveness.Methods:A decision-Markov model was constructed by using software TreeAge pro 2019 to simulate the outcomes of hepatitis C disease pregression of 100 000 persons aged 20-59 years. The cost-effectiveness of the strategies were evaluated from societal perspectives by using incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). One-way sensitivity analysis and probability sensitivity analysis were used to evaluate the uncertainty of parameters and model.Results:Hepatitis C screening was cost-effective in people aged 20- 59 years and the cost effectiveness was best in age group 40-49 years. Compared with non-screening strategy of hepatitis C in people aged 20-59 years, the incremental cost was 161.24 yuan, the incremental utility was 0.003 6 quality adjusted life years (QALYs)/per person, ICER was 45 197.26 yuan/QALY, ICER was less than the willing payment threshold. The ICER and NMB in all age groups were 42 055.06-53 249.43 yuan/QALY and 96.52-169.86 yuan/per person. Hepatitis C screening in people aged 40-49 years had the best cost-effectiveness. The results of one-way sensitivity analysis showed that the discount rate, anti-HCV detection cost, anti-HCV infection rate and the cost of direct antiviral agents were the main factors influencing economic evaluation. The results of the probability sensitivity analysis indicated that the model analysis was stable.Conclusions:Implementing hepatitis C screening based on medical institutions is cost-effective in people aged 20- 59 years, especially in those aged 40-49 years. Implementing the HCV screening strategy of be willing to test as far as possible in general population can reduce hepatitis C disease burden in China.

【Objective】 To investigate the effects of radical prostatectomy (RP) or brachytherapy (BT) on the prognosis of patients with high-risk prostate cancer as initial treatment, in order to provide a reference for the selection of clinical treatment options. 【Methods】 The clinical data of 133 191 patients diagnosed with high-risk prostate cancer and treated with RP or BT during 2005 and 2014 were extracted from the SEER database.The 5-year and 10- year cancer-specific survival (CSS) and overall survival (OS) were compared with K-M analysis and univariate and multivariate Cox regression.The clinical data of another 253 patients diagnosed with high-risk prostate cancer in Subei People’s Hospital during 2015 and 2020 were collected, including 153 patients who received RP and 100 patients who received BT.The 5-year biochemical progress-free survival (bPFS) and CSS were compared with K-M analysis. 【Results】 Univariate analysis of SEER data showed that BT was associated with a higher risk of death (HR=1.319, 95%CI: 1.256-1.386, P<0.001); age, marital status and TNM stage were associated with higher risk of death (P<0.001).Multivariate analysis, adjusted for relevant variables, showed that BT did not result in a higher risk of death compared with RP (HR=0.964, 95%CI:0.924-0.996, P=0.808). The OS curve showed that the longer the observed survival time, the better OS of RP as compared to BT (P<0.001); however, the CSS survival curve showed that the longer the observed survival time, the better CSS of BT compared to RP (P<0.001).The single-center data analysis showed no significant difference between BT and RP in the 5-year bPFS (P=0.263) and CSS (P=0.946). 【Conclusion】 For patients with high-risk prostate cancer, there is a significant difference in the prognosis of the two treatments if there is no adjustment of age, marital status, TNM stage and other factors, and the efficacy of RP is better than that of BT, especially in patients with survival more than 10 years.However, there is no statistically significant difference in the prognosis after the possible confounding factors are adjusted.Therefore, the initial treatment choice for these patients should be weighed from multiple perspectives, and patients’ choices must be respected after they are fully informed.

Objective To investigate the effects of remote ischemic conditioning(RIC)on neurological function,brain injury markers and vascular inflammatory mediators in patients with acute ischemic stroke(AIS)after intravenous thrombolysis.Methods Ninety AIS patients admitted to the Department of Neurology of Zhengzhou Central Hospital Affiliated to Zhengzhou University from May 2022 to October 2022 were selected as the research subjects.The patients were divided into the RIC group(n=29),the pseudo-RIC group(n=30)and the control group(n=31)according to the treatment method.All patients in the three groups were treated with intravenous thrombolysis with alteplase.After 24 hours of thrombolysis,the patients in the RIC group were given RIC treatment,the patients in the pseudo-RIC group were given pseudo-RIC treatment,and the patients in the control group were not given RIC treatment.All patients in the three groups were treated for 14 days.Clinical data of patients in the three groups were collected,including age,gender,and history of smoking,drinking,hypertension,diabetes mellitus,coronary artery disease and stroke.About 4-5 mL of the fasting peripheral venous blood was drawn from the patients within 24 hours after admission to the hospital and was centrifuged to obtain the serum.The levels of triacylglycerol(TG),total cholesterol(TC),glycated hemoglobin(HbA1c)and serum creatinine(Scr)were detected;the levels of fibrinogen(FIB)and D-dimer were detected by using a blood coagulation analyzer.The peripheral venous blood(4-5 mL)was drawn from the patients in the three groups before treatment and on the 7th and 14th days of treatment and was centrifuged to obtain the serum.The levels of S100 calcium-binding protein β(S100β),lipoprotein-associated phospholipase A2(Lp-PLA2)and interleukin(IL)-6 were detected by using the enzyme-linked immunosorbent assay(ELISA).The neuron specific enolase(NSE)level was detected by using the double antibody sandwich ELISA.The National Institutes of Health Stroke Scale(NIHSS)and the modified Rankin scale(mRS)were used to assess the neurological impairment of patients in the three groups.The adverse reactions during RIC treatment in the three groups were recorded.Results The overall effective rates of patients in the control group,pseudo-RIC group and RIC group were 90.32％(28/31),90.00％(27/30)and 100.00％(29/29),respectively;there was no statistically significant difference in the overall effective rate among the three groups(x2=3.059,P＞0.05).There was no statistically significant difference in the serum TG,TC,HbA1c,Scr,FIB and D-dimer levels of patients among the control group,pseudo-RIC group and RIC group before treatment(P＞0.05).Before treatment,there was no statistically significant difference in the serum Lp-PLA2,IL-6,S100β and NSE levels among the three groups(P＞0.05).The serum Lp-PLA2,IL-6,S100β and NSE levels of patients on the 7th and 14th days of treatment were significantly lower than those before treatment in the three groups(P＜0.05).On the 7th and 14th days of treatment,the serum Lp-PLA2,IL-6,S100β and NSE levels of patients in the RIC group were significantly lower than those in the pseudo-RIC group and control group(P＜0.05),and these indexes showed no statistically significant difference between the control group and the pseudo-RIC group(P＞0.05).There was no statistically significant difference in the NIHSS and mRS scores of patients among the three groups before treatment(P＞0.05).The NIHSS scores on the 7th and 14th days of treatment and the mRS scores on the 14th,90th days of treatment of patients were significantly lower than those before treatment in the three groups(P＜0.05).The NIHSS score on the 14th day of treatment and the mRS score on the 90th day of treatment in the RIC group were significantly lower than those in the pseudo-RIC group and control group(P＜0.05);there was no significant difference in the NIHSS and mRS scores between the control group and the pseudo-RIC group at each time points(P＞0.05).In the RIC group,2 patients developed upper limb pain and numbness during the treatment,and the symptoms disappeared after the treatment was suspended;no adverse reactions occurred in the pseudo-RIC group and the control group.Conclusion RIC therapy after intravenous thrombolysis can significantly promote neurological recovery,attenuate brain damage,and reduce the expression levels of vascular inflammatory mediators and brain damage markers in patients with AIS.

Objective:To investigate the effect and mechanism of the V-set and immunoglobulin domain-containing 4 ( VSIG4 ) gene mutation on the function of microglia in retinitis pigmentosa (RP). Methods:Localization of VSIG4 in the retina was detected by immunofluorescence.HMC3 cells (human microglial cells) were transfected with wild-type (Len-WT) VSIG4 gene, mutant type (Len-Mut) VSIG4 gene and empty vector virus (Len-Cont) and stimulated by the presence or absence of lipopolysaccharide (LPS), then divided into control group, LPS-Len-Mut group, LPS-Len-WT group, LPS-Len-Cont group, Len-Mut group, Len-WT group and Len-Cont group.The mRNA expression levels of the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by real-time fluorescence quantitative PCR.Protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4), nuclear transcription factor-κB (NF-κB) p65 subunit (P65), and phosphorylated P65 (PP65) were detected by Western blot.Cell phagocytic function was detected by phagocytosis assay.Cell migration ability was detected by cell scratch and transwell migration assay.LPS- stimulated HMC3 cells were co-cultured with 661W cells (mouse retinal photoreceptor cells), and the expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins of the cells were detected by Western blot.The number of apoptotic cells was determined by apoptosis assay. Results:VSIG4 was localized to microglia in mouse retina.The real-time fluorescence quantitative PCR results showed that compared with LPS-Len-WT group, the relative expression levels of IL-1β and TNF-α mRNA in HMC3 cells were significantly increased in LPS-Len-Mut group (both at P<0.05).The Western blot results showed that compared with LPS- Len-WT group, the protein expression levels of Nrf2, HO-1, and GPX4 in HMC3 cells were significantly reduced in LPS-Len-Mut group, and the PP65/P65 ratio was significantly increased (all at P<0.05).The phagocytic experiment results showed that the phagocytic rates of HMC3 cells in Len-Cont group, LPS-Len-Cont group, LPS-Len-WT group, and LPS-Len-Mut group were (35.67±3.22)%, (63.67±10.07)%, (84.00±3.46)%, and (64.67±2.31)%, respectively, showing a statistically significant difference ( F=59.06, P<0.001).Compared with LPS-Len-WT group, the phagocytic rate of HMC3 cells was significantly reduced in LPS-Len-Mut group ( P<0.05).The results of cell scratch and transwell migration assay showed that compared with LPS-Len-WT group, the migration rate of HMC3 cells at 24 and 48 hours and the number of invading cells per unit area at 24 hours were significantly reduced in LPS-Len-Mut group (all at P<0.05).Compared with LPS-Len-WT group, the expression ratio of Bax/Bcl-2 protein and the number of cell apoptosis were significantly increased in the LPS-Len-Mut group under the co-culture system (both at P<0.05). Conclusions:VSIG4 is localized to mouse retinal microglia.When the VSIG4 gene in RP mutates, HMC3 cells under LPS stimulation exhibit a series of changes, including activation of the NF-κB signaling pathway, decreased activation of the Nrf2/HO-1 signaling pathway, increased secretion of inflammatory cytokines, reduced phagocytic and migratory abilities, and increased cell apoptosis in co-culture systems.

Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein(FTO)in the ferroptosis in testicular interstitial cells induced by di(2-ethylhexyl)phthalate(DEHP).Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group(corn oil)and 3 dosed DEHP treatment groups(5,250 and 500 mg/kg),and received an intragastric infusion of corresponding agents for 35 d,respectively.After mouse testicular interstitial TM3 cells was treated with 0,100,200 and 400 μmol/L mono-2-ethylhexyl phthalate(MEHP)for 24 h,corresponding plasmids were transfected to construct Fto overexpressing TM3 cells.Serum testosterone level was detected by ELISA,expression of testicular proteins was detected with immunohistochemical assay,and contents of Fe2+,malondialdehyde(MDA)and lipid peroxides in the testicle were detected by colorimetry.Methylated RNA immunoprecipitation,RT-PCR,and Western blotting were used to detect the level of N6-methyladenosine(m6A)modification.Results In the mice exposed to 250 and 500 mg/kg DEHP,the serum testosterone level was significantly reduced(P＜0.01),contents of Fe2+,MAD and lipid peroxides in testicular tissue were obviously increased(P＜0.01),and protein levels of RNA demethylase FTO,and ferroptosis related molecules ferritin heavy chain 1(FTH1)and glutathione peroxidase 4(GPX4)were significantly down-regulated(P＜0.05),while those of transferrin receptor(TFRC),ferroportin(FPN),cyclooxygenase-2(COX-2),and acyl-CoA synthetase long-chain family member 4(ACSL4)were notably up-regulated(P＜0.05).MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells,increased production of intracellular reactive oxygen species(ROS),reduced mitochondrial membrane potential(MMP)(P＜0.01),down-regulated mRNA and protein levels of Fto(P＜0.01),and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue,indicating ferroptosis in testicular interstitial cells.Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells(P＜0.05),and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA(P＜0.05).Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.

Chronic fatigue syndrome(CFS)is a chronic comprehensive disease with a slow course and often accompanied by a variety of physical and psychiatric symptoms.At present,the incidence rate is on the rise.Based on the theory of"qi-pulse smooth and unobstructed",the pathogenesis of CFS is considered to be the loss of spleen and kidney and the deficiency of qi-pulse as the root;liver and lung disorders,qi-pulse stagnation as the pivot;wind fire invasion,phlegm blood stasis as the superficiality.Treatment should focus on tonifying the spleen and tonifying the kidneys to treat its root cause.According to the degree of deficiency of spleen and kidney and the emphasis of deficiency of qi-blood yin-yang,Buzhong Yiqi Decoction,Guipi Decoction,Shengyang Yiwei Decoction,Linggui Zhugan Decoction and Shenqi Pills should be selected flexibly.The methods of soothing the liver and regulating the lungs to regulate their pivot,harmonizing the liver and lungs,and using both ascending and descending functions should be used.Chaihu Shugan Powder,Xiaoyao Powder,Sini Powder,Guizhi Decoction,Shengmai Powder,etc.could be selected flexibly according to the disease location and disease focus.Clearing wind and clearing heat,eliminating phlegm and promoting blood circulation should be used to treat its superficiality,emphasizing tonifying deficiency and resolving depression.According to the different pathogenesis of patients,the corresponding treatment method should be flexibly chosen to supplement with medication.One medical case was attached in this article as the evidence,in order to provide reference for the TCM treatment of CFS.

【Objective】 To explore the clinical efficacy and safety of pelvic floor magnetic and electrical stimulation combined with Kegel exercise training in the treatment of stress urinary incontinence (SUI) after minimally invasive surgery for benign prostatic hyperplasia (BPH). 【Methods】 A total of 52 patients with SUI after minimally invasive surgery for BPH treated during Jan.2016 and Feb.2022 were randomly divided into test group (n=26) and control group (n=26). The test group received pelvic floor magnetic and electrical stimulation and Kegel exercise training, while the control group received Kegel exercise training only. The treatment lasted for 3 months. The scores of International Consultation on Incontinence Modular Questionnaire Short Form (ICIQ-SF), 1 h pad test, International Prostate Symptom Score (IPSS) and Incontinence Quality of Life Questionnaire (I-QoL) were recorded and compared between the two groups before and after treatment. The adverse reactions were observed. 【Results】 The scores of ICIQ-SF, IPSS and I-QoL and 1 h pad test significantly decreased in both groups after treatment (P<0.05). Before treatment, there were no significant differences of the above indicators between the two groups (P>0.05), but after treatment, the scores of ICIQ-SF,IPSS,I-QoL and 1 h pad test were significantly lower in the test group than in the control group (P<0.05). No severe adverse reactions were observed. 【Conclusion】 Pelvic floor magnetic stimulation combined with Kegel exercise training is safe and effective for SUI after minimally invasive surgery for BPH.

Objective:To detect the levels of γ-glutamyl transferase (GGT) in the amniotic fluid of normal pregnancies at 19-23 +6 gestational weeks and to analyze the changes in GGT level with gestational age. Methods:This study retrospectively collected the amniotic fluid supernatant from 383 singleton pregnant women (102, 103, 82, 68 and 28 cases at 19-19 +6, 20-20 +6, 21-21 +6, 22-22 +6, 23-23 +6 weeks of gestation, respectively) who underwent amniocentesis for prenatal diagnosis but had normal genetic diagnosis results in Cheeloo Hospital of Shandong University from January 2021 to September 2022. The levels of GGT in the amniotic fluid supernatant were tested and the statistical parameters including xˉ± s, min-max, median ( M), P1, P2.5, P5, P95, P97.5 and P99 values of GGT levels at each gestational week were calculated. GGT were non-normal data and converted into natural logarithms (lnGGT), and a least square linear regression equation was established to analyze the relationship between lnGGT and gestational week. Results:At 19-19 +6, 20-20 +6, 21-21 +6, 22-22 +6, and 23-23 +6 gestational weeks, the xˉ± s of amniotic fluid GGT were (385.8±235.7), (331.8±219.4), (253.7±197.9), (226.7±166.4), and (155.3±96.8) U/L, and the weekly declines were 14.0%, 23.5%, 10.6%, and 31.5%, respectively; the M values were 311.0, 288.0, 199.0, 160.5, and 105.5 U/L, and the weekly declines were 7.4%, 30.9%, 19.3%, and 34.3%, respectively; the P1- P99 were 67.1-1 404.5, 63.2-1 189.1, 36.0-849.8, 44.0-787.3, and 32.0-375.6 U/L, respectively. lnGGT was negatively correlated with gestational age ( R 2=0.148, P<0.001). Conclusions:In normal pregnancies at 19-23 +6 gestational weeks, GGT levels in amniotic fluid decrease with gestational age. Therefore, gestational age should be considered when establishing the reference value for amniotic fluid GGT in normal pregnancies.

Review of historical literature showed that the understanding of the indicated disease location of Modified FuMai Decoction （复脉汤加减方） has evolved from the upper jiao （焦） to the middle and lower jiao. Initially， it is used for the treatment of yin deficiency of both yin and yang in the upper jiao， changes to supplement stomach and produce fluids in the middle jiao， and is used to protect yin， clear the pathogens， conslidate yin and subdue yang so as to store the true yin of lower jiao. The unchanging principle of Fumai Decoction modifications is nourishing yin， while the changing aspects are determining the secondary treatment methods based on disease location of sanjiao， concomitant disease natures， internal injury or external contraction， warm disease or cold damage， thereby choosing the corresponding added or subtracted herbs， and providing reference for the application of classical formulas.

In the perspective of the theory of “circular movement of yang qi ascending and descending”， the author explores the four-season pathogenesis and treatment of insomnia based on the seasonal changes of the body's yin-yang balance. It is believed that the core pathogenesis of insomnia lies in the spleen and stomach deficiency and the internal buildup of dampness. The four-season pathogenesis of insomnia focuses can be categorized into four aspects： abnormal ascending of yang qi in the spring， leading to the liver fire inflammation or the liver qi stagnation； Predominance of yang qi in the upper side of the heart and gallbladder fire in the summer； Lung disorder and abnormal descent of yang qi， resulting in yang-heat conversion into dryness or disharmony between nutrient qi and defensive qi； Abnormal hiding of yang qi， manifesting as floating yang or deficiency in both yin and yang in the winter. It is advocated to dynamically grasp the pathogenesis of insomnia in accordance with the changes in time. A treatment framework called “restoring ascending and descending of yang qi” is proposed， with the core focus on resolving dampness and strengthening the spleen， while also addressing the liver and strengthen the spleen， clearing and descending the heart and gallbladder， purifing and descending the lung qi， and suppressing hyperactive the yang and invigorating the kidneys in different seasons. This enrichment of the traditional Chinese medicine time medicine research in insomnia treatment， based on the characteristics of seasonal rhythmic time， aims to better serve clinical practice and provide ideas for the clinical diagnosis and treatment of insomnia.