Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

AIM: To evaluate the safety and efficacy of allogeneic intrastromal lenticule implantation combined with corneal collagen cross-linking(CXL)in patients with moderate to advanced keratoconus.METHODS: A retrospective case series analysis was conducted. A total of 19 patients(20 eyes)with moderate to advanced keratoconus who underwent combined allogeneic intrastromal lenticule implantation and CXL at the Jinan Mingshui Eye Hospital from June 2021 to December 2023 were included. The uncorrected distance visual acuity(UCVA), thinnest corneal thickness, central corneal epithelial thickness, anterior corneal flat keratometry(Kf), steep keratometry(Ks), and mean keratometry(Km), as well as the first applanation time(A1T), the first applanation length(A1L), the velocity during the first applanation moment(VIN), the second applanation time(A2T), the second applanation length(A2L), the velocity during the second applanation moment(VOUT), highest concavity time(HCT), highest concavity radius(HCR), peak distance(PD), deformation amplitude(DA), stiffness parameter at first applanation(SP-A1), integrated radius(IR), central corneal thickness(CCT), intraocular pressure(IOP), corneal thickness-corrected IOP, biomechanically intraocular pressure IOP(bIOP), and corneal thickness variation rate(ARTH)were compared between the two groups before surgery and at 1 wk, 1, 3 and 6 mo after surgery.RESULTS: All patients successfully completed the surgery without any intraoperative complications. No significant differences were observed between pre-operative and post-operative measurements for UCVA or the corneal biomechanical parameters, including A1L, A2L, PD, A1T, A2T, VIN, VOUT, DA, IOP, and bIOP(all P>0.05). Significant differences were found between pre-operative and post-operative values for corneal thinnest point thickness, central corneal epithelial thickness, Kf, Ks, Km, and the corneal biomechanical parameters, including HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.05). The anterior corneal curvature demonstrated an initial increase followed by a decrease post-operatively. Furthermore, significant differences were observed between pre-operative and post-operative values for HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.005).CONCLUSION: Allogenic intrastromal lenticule implantation combined with corneal collagen cross-linking demonstrates favorable safety and stability in treating moderate-to-advanced keratoconus. This combined procedure effectively increases corneal thickness and rigidity, resulting in corneas that are more resistant to deformation postoperatively.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research. METHODS From September 2021 to September 2023， fracture patients admitted to 33 medical institutions were collected retrospectively. Patients who received conventional treatment were divided into control group （n＝3 750）， and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group （n＝ 3 706）. Self-reported indicators of patients were collected through telephone follow-up at 0， 4， 7 and 14 days after treatment. The improvement values of pain score， swelling score and health utility value， as well as effective rate and adverse drug reactions were compared between 2 groups. The propensity matching score （PSM） method was adopted to perform baseline matching on patient’s age， gender， fracture site， fracture severity， surgical type， type of hospital， and other indicators. Statistical analysis was performed on each therapeutic effect indicator. RESULTS After PSM， a total of 6 425 patients were included， of which 3 055 were in the observation group and 3 370 were in the control group. After 14 days of treatment， the observation group showed significant improvement in pain score （4.768 vs. 4.353）， swelling fangshiyuan2008@126.com grading score （2.979 vs. 2.391）， and life quality utility value （0.430 vs. 0.363）， as well as effective rate （87.20% vs.75.99%） compared to the control group （P＜0.05）. The results of subgroup analyses conducted by gender， age， hospital type， and fracture site were consistent with the aforementioned results. In terms of safety， the observation group had no serious adverse reactions， with a total of 29 cases of mild adverse reactions such as dizziness， stomach pain， and allergies， with an incidence rate of 0.78%. CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain， swelling， quality of life， and effective rate in patients with fractures， and have good safety.

Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.

Objective:To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification.Methods:A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically.Results:There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P<0.001). Conclusions:GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

【Objective】 To understand factors associated with children′s attendance at nursery care institutions (NCIs) and the basic characteristics of the NCIs children were enrolled in, so as to provide scientific evidence for policymakers. 【Methods】 During November 2020 and January 2021, parents who visited the Department of Child Health Care in six selected maternal and children′s hospitals, as well as nearby NCIs in Zhejiang were invited to finish an online questionnaire. Information such as children′s sociodemographic characteristics, parents′ knowledge, attitude and practice regarding nursery and feeding, etc. were collected. A total of 1 756 questionnaires were collected. 【Results】 Compared to children who were not in NCIs, children enrolled in NCIs were older (94.4% of children ≥24 months vs. 30.1%, χ²=835.27), more likely to be from the local area (87.2% vs. 81.4%,χ²=12.25), more likely to have parents with a college degree (mother: 83.6% vs. 74.2%, χ²=35.29; father: 79.9% vs. 70.0%, χ²=27.01), had a higher prevalence of family annual income >200 000 CNY (49.5% vs. 28.2%, χ²=110.49), and were less likely to have their grandparents available to take care of them (16.7% vs. 26.8%, χ²=31.4) The difference all have great significant.(P<0.05). In a multivariate Logistic regression model, the older the child, the more likely they were to attend an NCI (for children aged 6 - 23 months, OR=6.70; for children aged 24 - 35 months, OR=134.03; and for children aged 36 - 42 months, OR=699.33; P<0.05). Family annual income was positively associated with children′s attendance at NCIs (for those earning 100 000 - 200 000 CNY/year, OR=1.63; for those earning 200 000 - 500 000 CNY/year, OR=2.96; and for those earning >500 000 CNY/year, OR=4.62, P<0.05). Conversely, the higher the level of grandparent involvement in daily care, the lower the attendance at NCIs (for children cared for by both parents and grandparents, OR=0.57; for those primarily cared for by grandparents, OR=0.26, P<0.05). For children who used to stay at NCIs, 82.8% stayed at institutions that only recruited children aged 0 - 3 years, 97.4% spent their whole day in NCIs, and 71.4% spent less than 3 000 CNY per month for NCI services. Additionally, over 95% of parents were satisfied with the food and care services in NCIs, as well as their children′s physical development in NCIs. However, 32.1% of NCIs were reported by parents as having no room for breastfeeding. 【Conclusions】 Children′s age, grandparent involvement in routine care, and family annual income are the main factors associated with children′s attendance at NCIs. There is a greater need for more affordable and community-based NCIs, particularly for children under 2 years old. Additionally, more attention should be paid to the quality surveillance, assessment and management of NCIs.

Objective To investigate the effect and mechanism of naringin on acute lung injury(ALI)in septic mice.Methods The acute lung injury mouse model of sepsis was established by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide.The mice were randomly divided into control group(injected with equal amounts of saline and phosphate buffer),model group(mouse model of sepsis acute lung injury),naringin group(50 mg·kg-1 naringin injected intraperitoneally 1 hour prior to lipopolysaccharide modeling)and BzATP group(50 mg·kg-1 naringin+5 mg·kg-1 BzATP injected intraperitoneally 1 hour prior to lipopolysaccharide modeling).After modeling,lung tissues were taken 24 h later,lung coefficients were calculated;lung tissue interleukin(-ILβ-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay;the expression of purinergic 2X7 receptor(P2X7R),nucleotide-binding oligomerization structural domain-like receptor protein 3(NLRP3)and nuclear factor-κB(NF-κB)proteins were detected by Western blotting.Results The lung coefficients in the control,model,naringin and BzATP groups were(6.26±0.31),(9.09±1.02),(7.02±0.45)and(8.79±0.55)mg·g-1;the contents of TNF-α were(56.41±0.35),(174.68±1.58),(85.23±1.68)and(162.97±3.42)pg·mL-1;the contents of IL-1β were(44.18±7.37),(119.91±17.16),(85.41±2.14)and(104.57±3.39)pg·mL-1;the contents of IL-10 were(50.82±2.89),(28.31±1.86),(42.82±1.98)and(25.19±1.69)pg·mL-1;P2X7 protein expression levels were 0.45±0.16,1.33±0.10,0.64±0.09 and 1.05±0.18;NF-κB protein expression levels were 0.38±0.19,1.29±0.09,0.57±0.11 and 0.92±0.07;NLRP3 protein expression levels were 0.72±0.14,1.28±0.23,0.75±0.09 and 1.27±0.23.Compared with the model group in the control group and naringin group,compared with the naringin group in the BzATP group,the differences of the above indexes were statistically significant(P＜0.01,P＜0.05).Conclusion Naringin attenuates acute lung injury in septic mice by inhibiting the P2X7 receptor-mediated NF-κB/NLRP3 signaling pathway.