Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides.

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

Implementation of Individualized Low-Dose Computed Tomography-Guided Hook Wire Localization of Pulmonary Nodules: Feasibility and Safety in the Clinical Setting.

Background: CT-guided hook-wire localization is an essential step in the management of small pulmonary nodules. Few studies, however, have focused on reducing radiation exposure during the procedure. Purpose: This study aims to explore the feasibility of implementing a low-dose computed tomography (CT)-guided hook wire localization using tailored kVp based on patients' body size. Materials and Methods: A total of 151 patients with small pulmonary nodules were prospectively enrolled for CT-guided hook wire localization using individualized low-dose CT (LDCT) vs. standard-dose CT (SDCT) protocols. Radiation dose, image quality, characteristics of target nodules and procedure-related variables were compared. All variables were analyzed using Chi-Square and Student's t-test. Results: The mean CTDIvol was significantly reduced for LDCT (for BMI ≤ 21 kg/m2, 0.56 ± 0.00 mGy and for BMI > 21 kg/m2, 1.48 ± 0.00 mGy) when compared with SDCT (for BMI ≤ 21 kg/m2, 5.24 ± 0.95 mGy and for BMI > 21 kg/m2, 6.69 ± 1.47 mGy). Accordingly, the DLP of LDCT was significantly reduced as compared with that of SDCT (for BMI ≤ 21 kg/m2, 56.86 ± 4.73 vs. 533.58 ± 122.06 mGy.cm, and for BMI > 21 kg/m2, 167.02 ± 38.76 vs. 746.01 ± 230.91 mGy.cm). In comparison with SDCT, the effective dose (ED) of LDCT decreased by an average of 89.42% (for BMI ≤ 21 kg/m2) and 77.68% (for BMI > 21 kg/m2), respectively. Although the images acquired with the LDCT protocol yielded inferior quality to those acquired with the SDCT protocol, they were clinically acceptable for hook wire localization. Conclusions: LDCT-guided localization can provide safety and nodule detection performance comparable to SDCT-guided localization, benefiting radiation dose reduction dramatically, especially for patients with small body mass indexes.

Evaluation of diagnostic efficacy of NRP-1/CD304 in hematological diseases.

BACKGROUND: Previous studies had explored the diagnostic or prognostic value of NRP-1/CD304 in blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and B-cell acute lymphoblastic leukemia (B-ALL), whereas the expression and application value of NRP-1/CD304 in other common hematological diseases have not been reported. METHODS: Bone marrow samples from 297 newly diagnosed patients with various hematological diseases were collected to detect the expression of NRP-1/CD304 by flow cytometry (FCM). The diagnostic efficacy of NRP-1/ CD304-positive diseases was analyzed by receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) was compared. RESULTS: In the research cohort, the total positive rate of NRP-1/CD304 was 14.81% (44/297), mainly distributed in BPDCN (100%, 6/6), B-ALL (48.61%, 35/72), and AML (4.48%, 3/67), with statistically significant differences (p < 0.01). Other diseases, such as T-cell acute lymphoblastic leukemia (T-ALL), B-cell non-Hodgkin lymphoma (B-NHL), T/NK-cell lymphoma and plasma cell neoplasms, did not express NRP-1/CD304. The AUC of NRP-1/CD304 was 0.936 (95% CI 0.898-0.973), 0.723 (95% CI 0.646-0.801), and 0.435 (95% CI 0.435) in BPDCN, B-ALL and AML, respectively. Besides, CD304 was commonly expressed in B-ALL with BCR-ABL1 gene rearrangement (p = 0.000), and CD304 expression was positively correlated with CD34 co-expression (p = 0.009) and CD10 co-expression (p = 0.007). CONCLUSIONS: NRP-1/CD304 is only expressed in BPDCN, B-ALL and AML, but not in other common hematological diseases. This indicates that NRP-1/CD304 has no obvious diagnostic and follow-up study value in hematological diseases other than BPDCN, B-ALL, and AML.

Association Between Perivascular Adipose Tissue Density and Atherosclerosis in the Descending Thoracic Aorta.

Radiodensity measured by computed tomography (CT) in Hounsfield Units (HU) is emerging as a clinical tool for detecting perivascular adipose tissue (PVAT) inflammation. In the present study, we hypothesized that PVAT radiodensity might predict the risk of descending thoracic aorta atherosclerosis. A total of 73 subjects who underwent CT angiography to investigate aortic disease were retrospectively analyzed. PVAT radiodensity, aortic complex plaque (ACP), mean plaque-burden score (MPBS), and plaque density were measured, and the association between them was analyzed. Perivascular adipose tissue radiodensity (HU) in patients with different aortic plaques grades (grade 1, 2, 3, and 4) were -93.71 ± 2.50, -93.63 ± 3.93, -90.24 ± 4.49, and -89.90 ± 5.18, respectively, and the difference was significant (P = .010). In the regression analysis, PVAT radiodensity was an independent predictor of ACP, with an OR of 1.263. In the linear analysis, PVAT radiodensity was an independent predictor of MPBS, with a ß-coefficient of .073. In the univariate analysis, only the PVAT radiodensity was significantly associated with plaque density, with a ß-coefficient of -1.666. In conclusion, PVAT density was independently related to descending thoracic aorta atherosclerosis.

Association between exposures to phthalate metabolites and preterm birth and spontaneous preterm birth: A systematic review and meta-analysis.

Emerging evidence from observational studies proves the association between preterm birth (PTB) and phthalate metabolites; however, such findings are inconsistent and inconclusive. This meta-analysis aimed to clarify this association by accessing the connection between 11 phthalate metabolites and PTB, and 6 phthalate metabolites and spontaneous PTB. The PubMed, Embase, and WOS (Web of Science) databases were searched up to July 2020. Seven prospective studies met the inclusion criteria. Pooled odds ratios (OR) with 95 % confidence intervals (CIs) were calculated for risk estimation. Our results indicated that mono-n-butyl phthalate (MBP), sum of di-2-ethylhexyl phthalate (ΣDEHP), and mono 3-carboxypropyl phthalate (MCPP) significantly correlated with the risk of PTB (MBP: OR = 1.23, 95 % CI = 1.05-1.45; ΣDEHP: OR = 1.21, 95 % CI =1.01-1.44; MCPP: OR = 1.09, 95 % CI = 1.00-1.19). Pooled results showed that spontaneous PTB was associated with higher urinary levels of mono-ethyl phthalate (MEP), MCPP, mono-isobutyl phthalate (MIBP), and MBP (MBP: OR = 1.27, 95 % CI = 1.02-1.58; MEP: OR = 1.19, 95 % CI = 1.01-1.40; MCPP: OR = 1.15, 95 % CI = 1.02-1.30; MIBP: OR = 1.38, 95 % CI = 1.12-1.71). Overall, we conclude that during pregnancy, MBP, ΣDEHP, and MCPP levels are associated positively with PTB. MBP, MEP, MCPP, and MIBP levels had increased odds of spontaneous PTB. No significant associations were observed between other phthalate metabolites and PTB or spontaneous PTB. Further research is needed to verify these findings and elucidate the association of phthalate levels and PTB.

Pharmacological Validation of ASIC1a as a Druggable Target for Neuroprotection in Cerebral Ischemia Using an Intravenously Available Small Molecule Inhibitor.

Acidosis is a hallmark of ischemic stroke and a promising neuroprotective target for preventing neuronal injury. Previously, genetic manipulations showed that blockade of acid-sensing ion channel 1a (ASIC1a)-mediated acidotoxicity could dramatically alleviate the volume of brain infarct and restore neurological function after cerebral ischemia. However, few pharmacological candidates have been identified to exhibit efficacy on ischemic stroke through inhibition of ASIC1a. In this work, we examined the ability of a toxin-inspired compound 5b (C5b), previously found to effectively inhibit ASIC1a in vitro, to exert protective effects in animal models of ischemic stroke in vivo. We found that C5b exerts significant neuroprotective effects not only in acid-induced neuronal death in vitro but also ischemic brain injury in vivo, suggesting that ASIC1a is a druggable target for therapeutic development. More importantly, C5b is able to cross the blood brain barrier and significantly reduce brain infarct volume when administered intravenously in the ischemic animal model, highlighting its systemic availability for therapies against neurodegeneration due to acidotoxicity. Together, our data demonstrate that C5b is a promising lead compound for neuroprotection through inhibiting ASIC1a, which warrants further translational studies.

Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits.

The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired in adulthood. These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the MEC and nectin3 level in the CA1. Postnatal suppression of nectin1 but not nectin3 level in the MEC impaired spatial memory, whereas conditional inactivation of nectin1 from MEC excitatory neurons reproduced the adverse effects of early-life stress on MEC-dependent memories and neuronal plasticity in CA1. Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits.

Associations Between Polybrominated Diphenyl Ethers Concentrations in Human Placenta and Small for Gestational Age in Southwest China.

BACKGROUND: Prenatal exposures to polybrominated diphenyl ethers (PBDEs) may affect fetal growth. Small for gestational age (SGA) is a measure based on birth weight and gestational age at birth and represents a good indicator of fetal growth but it has been used only in a small number of studies. The present study aimed to examine the associations between PBDEs exposure and the risk of SGA among participants from a birth cohort in Southwest China. METHODS: The concentrations of eight common PBDE congeners (BDE-28, BDE47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209) in 996 human placental samples collected between May to October 2020 were determined. A questionnaire survey was administered regarding maternal characteristics. The outcome data of the newborns were obtained from the medical record. The Mann-Whitney U test and binomial logistic regression analysis were used to assess associations between PBDEs concentrations (as a continuous or categorical variable) and SGA. RESULTS: All PBDE congeners were detected in more than 73% of samples. The median concentrations of ΣPBDEs were 10.08 ng/g lipid weight (lw). BDE-209 was the most abundant PBDE congener, contributed 28% to ΣPBDEs. There were 114 (11.4%) SGA infants. The levels of BDE-99, BDE-100, BDE-209, and the total levels of ΣPBDEs in the SGA group were significantly higher than those in the controls. When classifying the PBDEs concentrations as two categories: low and high, high level of ΣPBDEs was associated with increased risk of SGA [odds ratio (OR): 2.203, 95% confidence interval (CI): 1.453-3.340] after adjusting for potential covariates. The association remained significant when stratifying the data by gender of the newborn (OR: 2.572, 95% CI: 1.337-4.947 for boys; OR: 2.385, 95% CI: 1.315-4.325 for girls). CONCLUSION: The present study adds to the literature by using placenta to measure PBDEs exposure during pregnancy, and provides evidence that prenatal exposure to PBDEs may be associated with the risk of SGA, at least at the levels of exposure in our population.

[Perioperative Antiplatelet Therapy in Patients with Coronary Stents Undergoing Elective Non-Cardiac Surgery].

Among patients undergoing elective non-cardiac surgery (NCS), those with coronary stent implants are gradually becoming a patient group that cannot be easily overlooked. Previous history of heart disease, coronary stents and antiplatelet agents expose these patients to dual perioperative risks of thrombosis and bleeding. Formulating appropriate plans for perioperative antiplatelet therapy will help reduce the risks and ensure the safety of patients. We herein reviewed and analyzed various aspects of perioperative antiplatelet therapy for patients with coronary stent implants undergoing elective NCS, and discussed prospective research directions in the field.

Tuberculosis treatment delay and nosocomial exposure remain important risks for patients undergoing regular hemodialysis.

BACKGROUND AND OBJECTIVE: Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case-control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients. METHODS: Adult (aged ≥20 years) patients with incident ESRD over 2000-2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio. RESULTS: Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p < 0.001). Nosocomial exposure increased active TB risk (adjusted odds ratio [OR; 95% confidence interval, CI]: 1.60 [1.55-1.66] per month of exposure), particularly when the exposure time was either within 6 months before the index case was diagnosed or 6-15 months before the ESRD patient became an incident active TB case. For patients with active TB, cough-related medication prescriptions (proxy for cough symptoms) exponentially increased over 6 months before TB treatment. CONCLUSION: Nosocomial exposure attributed to delay in the diagnosis of index pulmonary TB is important in TB transmission among patients undergoing regular hemodialysis. Additional studies investigating how TB can be diagnosed and treated early are warranted. SUMMARY AT A GLANCE: Our study revealed that nosocomial exposure, attributed to delay in pulmonary TB diagnosis, is important in TB transmission among patients undergoing regular hemodialysis. Strategies to diagnose and treat TB early are crucial to infection control, and they warrant further investigations.

A rare complication of pelvic perforation by an excessive medial slide of the helical blade after treatment of an intertrochanteric fracture with proximal femoral nail anti-rotation: A case report and literature review.

Intertrochanteric fractures have become a severe public health problem in elderly patients. Proximal femoral nail anti-rotation (PFNA) is a commonly used intramedullary fixation device for unstable intertrochanteric fractures. Pelvic perforation by cephalic screw is a rare complication. We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture. The patient underwent surgery with PFNA as the intramedullary fixation device. Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation. We performed a cemented total hip arthroplasty as the savage procedure. At the latest follow-up of 12 months after total hip arthroplasty, the patient had no pain or loosening of the prosthesis in the left hip. Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device, especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation. The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.

Hemodialysis acutely altered interferon-gamma release assay test result and immune cell profile.

Patients receiving hemodialysis (HD) are at risk of TB development. IGRA-positive patients showed significant decrease in quantitative IGRA result with alterations in CD3+CD4+CD45RO+, NK cell, and monocyte subsets immediately upon HD procedure. Our result suggested that the timing of IGRA testing is crucial in end-stage renal disease population.

A nerve conduit filled with Wnt5a-loaded fibrin hydrogels promotes peripheral nerve regeneration.

AIMS: Peripheral nerve injury is a significant clinical problem with a substantial impact on quality of life, for which no optimal treatment has been found. This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect. METHODS: The Wnt5a-loaded fibrin hydrogel was synthesized by mixing a Wnt5a solution with thrombin and fibrinogen solutions. The loading capacity and release profile of Wnt5a-loaded fibrin hydrogel and the effect of Wnt5a on Schwann cells were evaluated in vitro. We also assessed the in vivo repair status via histological analysis of the regenerative nerve and gastrocnemius muscle, electrophysiological examination, gait analysis, and muscle wet weight. RESULTS: We developed a nerve conduit filled with Wnt5a-loaded fibrin hydrogel (Fn) as a sustained-release system to repair a 10-mm rat sciatic nerve defect. In vitro, Wnt5a could promote SC proliferation and the gene expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and cholinergic neurotrophic factor (CNTF), as well as the protein secretion of VEGF and NGF. In vivo, the Wnt5a/Fn group was superior to the hollow, fibrin hydrogel, and Wnt5a groups in terms of axonal growth, myelination, electrophysiological recovery, target organ innervation, and motor function recovery 12 weeks after the operation. CONCLUSION: The Wnt5a/Fn nerve conduit can promote peripheral nerve defect regeneration, with potential clinical applications. The mechanism for this may be the facilitation of multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.

The automated processing algorithm to correct the test result of serum neuron-specific enolase affected by specimen hemolysis.

INTRODUCTION: Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test. METHODS: The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots. RESULTS: The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = -0.069, p = 0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%). CONCLUSION: The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

Awareness regarding and vaccines acceptability of human papillomavirus among parents of middle school students in Zunyi, Southwest China.

The objective of this study was to investigate the parent cognition of information regarding the human papillomavirus (HPV) and their willingness toward HPV vaccination of their middle-school-aged children in Zunyi, Guizhou Province, China.The results provide a basis for improving the awareness concerning HPV-related information as a key vaccination strategy for implementing the HPV vaccine in the local context. Methods include the random cluster sampling method and questionnaires to survey parents. General descriptive and single-factor analyses were used to assess cognition to determine factors influencing vaccine willingness. Of 1,074 parents, 28.2% (302) and 38.0% (408) had heard of HPV and its vaccine before the survey, and when given HPV-related information, 73.9% (794) parents were willing to vaccinate their children. Reasons why parents did or did not want the vaccination were surveyed, with lack of sufficient knowledge about HPV and its vaccine being the primary reason to refuse vaccination. Concerns about safety, effectiveness, and perceiving low risk are the biggest obstacle in promoting vaccination. When the price is <1000, most parents (56.1%) are willing to vaccinate their children; thus, cost is also one of the concerns. Therefore, strategies for improving public awareness regarding the risk of cervical cancer and confidence in vaccination must be considered by policymakers.If the national authority confirms that the vaccine is safe and effective, the vaccine should be included in the national immunization program to increase publicity, address safety concerns, and allow for price regulation.

[Experience in treatment of cervical spondylotic radiculopathy by relaxing the sinew of hand three yang meridians with the tendon-bone needling therapy of Chinese medicine].

The clinical experience of professor WU Han-qing in treatment of cervical spondylotic radiculopathy (CSR) with the tendon-bone needling therapy of Chinese medicine is introduced. Professor WU believes that the pathogenesis of CSR is the damage on the neck and the sinew of hand three yang meridians, the formation of clustered nodules, obstruction in meridians and the stagnation of qi and blood. In treatment, the tendon-bone needling therapy is mainly adopted to relaxing clustered nodules and the sinew of hand three yang meridians and promoting qi and blood circulation. Regarding the acupoint selection, the "three-yangguan localization method" is used. The three hand-yangguan points and the three wrist-yangguan points are selected. The knotted points corresponding to the affected transverse processes of cervical vertebra are selected as well. Meanwhile, the adjuvant treatment points are selected on the base of the principle as "selecting the points along the affected meridian sinew". During treatment, according to needling sites and layers, the different needling techniques are optioned flexibly. Besides, the attentive experience in needling sensation in physician and the interaction between physician and patient are emphasized so as to improve the safety of treatment.

The noncanonical role of the protease cathepsin D as a cofilin phosphatase.

Cathepsin D (cathD) is traditionally regarded as a lysosomal protease that degrades substrates in acidic compartments. Here we report cathD plays an unconventional role as a cofilin phosphatase orchestrating actin remodeling. In neutral pH environments, the cathD precursor directly dephosphorylates and activates the actin-severing protein cofilin independent of its proteolytic activity, whereas mature cathD degrades cofilin in acidic pH conditions. During development, cathD complements the canonical cofilin phosphatase slingshot and regulates the morphogenesis of actin-based structures. Moreover, suppression of cathD phosphatase activity leads to defective actin organization and cytokinesis failure. Our findings identify cathD as a dual-function molecule, whose functional switch is regulated by environmental pH and its maturation state, and reveal a novel regulatory role of cathD in actin-based cellular processes.

Health economic evaluation of primary human papillomavirus screening in urban populations in China.

BACKGROUND: On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example. METHODS: We use an extensively validated platform ('Policy1-Cervix'), calibrated to data from Shenzhen city and Guandong Province. We evaluated a range of strategies that have previously been implemented as pilot studies in China, or recommended as guidelines within China and globally, spanning primary HPV, cytology and co-testing strategies. We additionally considered alternate triaging methods, age ranges and screening intervals, resulting in 19 algorithms in total. RESULTS: Of the 19 strategies considered, the most effective approach involved primary HPV testing. At 3- to 10-yearly intervals, primary HPV testing reduced the age-standardized cancer mortality rate by 37-71 %. The most cost-effective strategy was 5-yearly primary HPV testing with partial genotyping triage for ages 25-65, discharging to 10-yearly screening for low-risk women (ICER = US$7191/QALYS using 2018 costs; willingness-to-pay threshold<1xGDP [US$9771]). This strategy gave an incidence and mortality reduction of 56 % and 63 %, respectively. This remained the most cost-effective strategy under most conditions in sensitivity analysis. CONCLUSION: Primary HPV testing would be cost-effective in Shenzhen and could more than halve cervical cancer incidence rates to 6 per 100,000 over the long term. In order to achieve rates below 4 per 100,000, the elimination threshold set by the World Health Organization, vaccination will likely also be necessary.