[Three cases of occupational chronic chloropropene poisoning].

Chronic chloropropene poisoning is a disease mainly caused by peripheral nerve damage due to close contact with chloropropene in industrial production, its clinical manifestations include varying degrees of sensory, motor, or tendon reflex disorders in the distal limbs, and neuromyography can show neurogenic damage. This article analyzed and summarized the clinical characteristics, diagnosis and treatment methods of three patients with occupational chronic chloropropene poisoning, in order to enhance the clinical understanding of occupational chronic chloropropene poisoning and provide reference for clinical diagnosis and treatment.

Determining the optimal timing of adjuvant chemotherapy initiation after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Studies on several malignancies have suggested that the time to commencement of adjuvant chemotherapy (AC) is associated with survival outcomes. There have, however, been no relevant reports of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: This clinical study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was progression-free survival (PFS). Inverse probability of treatment weighting was used to control for confounding factors. Cox models with restricted cubic splines, Kaplan-Meier method and log-rank tests were used to evaluate the relationship between AC timing and survival. RESULTS: A total of 551 patients were identified [median age, 45 years (interquartile range 36-52 years); 383 (69.5%) male]. Restricted cubic splines demonstrated that the timing of AC initiation had a U-shaped association with PFS. The risk of disease progression decreased within 37 days and subsequently increased. From 37 to 90 days, each additional 7-day delay conferred worse PFS of 1.32 months {hazard ratio (HR): 1.14 [95% confidence interval (CI) 1.01-1.28], P = 0.04}. The cut-off value of the receiver operating characteristic curve for initiation was 69.5 days. At a median follow-up of 48 months, the PFS was significantly better in patients initiated within 69.5 days [HR: 2.18 (95% CI 1.17-4.06), log-rank P = 0.009], with a higher 3-year rate [78.8% (95% CI 75.1% to 82.7%) versus 59.0% (95% CI 42.2% to 82.5%)] than beyond 69.5 days. Positive results were also observed in secondary endpoints. The initiation group was an independent prognostic factor [HR: 2.28 (95% CI 1.42-3.66), P < 0.001]. CONCLUSIONS: The optimal timing of AC initiation is ∼37 days after concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. A delay beyond 69.5 days is associated with compromised survival. Efforts should be made to address the reasons for delays and ensure the timely initiation of AC.

Precise Measurement of Born Cross Sections for e

Using data samples collected with the BESIII detector at the BEPCII collider at center-of-mass energies ranging from 3.80 to 4.95 GeV, corresponding to an integrated luminosity of 20 fb^{-1}, a measurement of Born cross sections for the e^{+}e^{-}→D^{0}D[over ¯]^{0} and D^{+}D^{-} processes is presented with unprecedented precision. Many clear peaks in the line shape of e^{+}e^{-}→D^{0}D[over ¯]^{0} and D^{+}D^{-} around the mass range of G(3900), ψ(4040), ψ(4160), Y(4260), and ψ(4415), etc., are foreseen. These results offer crucial experimental insights into the nature of hadron production in the open-charm region.

[Huangqin Qingrechubi Capsule alleviates inflammation and uric acid and lipid metabolism imbalance in rats with gouty arthritis by inhibiting the PTEN/PI3K/AKT signaling pathway].

OBJECTIVE: To investigate the effects of Huangqin Qingrechubi Capsule (HQC) on inflammation and uric acid and lipid metabolism in rats with gouty arthritis (GA) and its mechanism. METHODS: SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline, colchicine and HQC at low, medium and high doses (n=10) by gavage for 7 days. Toe swelling of the rats was detected at 4, 8, 24, 48 and 72 h after modeling, and synovial histological changes were observed with HE staining. Serum levels of interleukin-10 (IL-10), IL-18, tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), adiponectin, leptin, resistin and visfatin were measured by ELISA, and the levels of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), and uric acid (BUA) were detected. RTqPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog (PTEN), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) and the protein expressions of PTEN, PI3K, p-PI3K, AKT and p-AKT. RESULTS: The rat models of GA showed obvious toe swelling, which reached the peak level at 48 h. HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia. The rat models showed significantly increased expressions of TNF-α, TGF-ß1, IL-18, TC, TG, leptin, resistin and visfatin, BUA, p-PI3K, and p-AKT and lowered levels of IL-10, APN, HDL-C, and PTEN. Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models. CONCLUSION: HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

[Qingshen Granules alleviates renal fibrosis in mice by regulating exosomes, miR-330-3p, and CREBBP expression].

OBJECTIVE: To explore the effects of Qingshen Granules (QSG) on adenine-induced renal fibrosis in mice and in uric acid (UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes, miR-330-3p and CREBBP. METHODS: A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks. An adenoassociated virus vector was injected into the tail vein, and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9, Hsp70, and TSG101 and expressions of Col-III, α-SMA, FN, and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining. In the cell experiment, NRK-49F cells were stimulated with uric acid (400 µmol/L) followed by treatment with QSG-medicated serum from SD rats, and the changes in expressions of the exosomal markers and Col-III, α-SMA, FN, and E-cad were analyzed. Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP, whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells. RESULTS: The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9, Hsp70, and TSG101, which were decreased by treatment with QSG. The expressions of Col-III, α-SMA, and FN increased and Ecad decreased in the mouse models but these changes were reversed by QSG treatment. QSG treatment obviously alleviated renal fibrosis in the mouse models. Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p, increased CREBBP levels, and reduced fibrosis in the mouse models. Dual luciferase assay confirmed CREBBP as a target of miR-330-3p, which was consistent with the results of the cell experiments. CONCLUSION: QSG inhibits renal fibrosis in mice by regulating the exosomes, reducing miR-330-3p levels, and increasing CREBBP expression.

[Linarin inhibits microglia activation-mediated neuroinflammation and neuronal apoptosis in mouse spinal cord injury by inhibiting the TLR4/NF-κB pathway].

OBJECTIVE: To investigate the mechanism underlying the neuroprotective effect of linarin (LIN) against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury (SCI). METHODS: Fifty C57BL/6J mice (8- 10 weeks old) were randomized to receive sham operation, SCI and linarin treatment at 12.5, 25, and 50 mg/kg following SCI (n=10). Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale, inclined plane test, and footprint analysis, and spinal cord tissue damage and myelination were evaluated using HE and LFB staining. Nissl staining, immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue. In cultured BV2 cells, the effects of linarin against lipopolysaccharide (LPS)­induced microglia activation, inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining, Western blotting, RT-qPCR, and ELISA. In a BV2 and HT22 cell co-culture system, Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation. RESULTS: Linarin treatment significantly improved locomotor function (P < 0.05), reduced spinal cord damage area, increased spinal cord myelination, and increased the number of motor neurons in the anterior horn of the SCI mice (P < 0.05). In both SCI mice and cultured BV2 cells, linarin effectively inhibited glial cell activation and suppressed the release of iNOS, COX-2, TNF-α, IL-6, and IL-1ß, resulting also in reduced neuronal apoptosis in SCI mice (P < 0.05). Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF- κB signaling pathway. In the cell co-culture experiments, linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells (P < 0.05). CONCLUSION: The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF­κB signaling pathway, which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.

[Study on the impact of aging on the brain activity patterns in auditory speech comprehension dual-route regions].

Objective: To elucidate the patterns of neural activity alterations associated with auditory speech comprehension across the lifespan and the impact of varying listening environments on these dynamics. Methods: Functional near-infrared spectroscopy (fNIRS) was employed to measure the concentration of oxygenated hemoglobin in the brains of 93 adults aged from 20 to 70 with normal hearing. These participants were recruited from Beijing Tongren Hospital, affiliated with Capital Medical University, between March 2021 and February 2023. Brain activity was recorded as subjects passively listened to sentences in both silent and noise conditions with varying signal-to-noise ratios (SNR). The alterations in brain activity were analyzed to delineate the age-related trends under different auditory conditions. Statistical analysis was performed using SPSS 22.0 software. Results: The bilateral primary auditory cortex, superior temporal gyrus, and Wernicke's area, critical for sound signal discrimination and perception, exhibited enhanced activity post-stimulus presentation. Broca's area, pivotal for speech production, demonstrated an initial decrease in activity followed by an increment after stimulus onset. The ventral middle temporal gyrus and dorsal postcentral gyrus showed augmented activity in later time windows. Furthermore, it was observed that in quiet conditions and at low noise levels (SNR=10 dB), auditory cortical activity diminished with age. With increasing noise levels (SNR=5 dB), compensatory brain regions (right ventral middle temporal gyrus and dorsal postcentral gyrus) showed enhanced activity with advancing age. As noise intensity further escalated (SNR=0, SNR=-5 dB), not only did auditory cortical activity decline, but also the activity in regions associated with semantic processing and motor functions reduced with age. Conclusion: During auditory speech comprehension, dual-pathway brain regions exhibit distinct activity patterns. With heightened noise exposure, an increasing number of brain regions are influenced by aging, manifesting as a general decline in activity in most dual-pathway regions, alongside a selective augmentation in some compensatory regions on the right hemisphere.

[Expression, purification and functional validation of phage depolymerase from hypervirulent Klebsiella pneumoniae serotype K1].

Objective: To express and purify the phage depolymerase from hypervirulent Klebsiella pneumoniae (hvKp) serotype K1 and validate its function. Methods: Phage that infected serotype K1-type hvKp was isolated from hospital sewage. The biology and morphology of the phage were determined by plaque assay and transmission electron microscopy. The whole genome of the phage was sequenced by the Illumina HiSeq 2500 platform. The presence of depolymerase was determined by observing the plaque halo. Bioinformatic analysis and prokaryotic protein expression system were further used to predict and identify phage depolymerase. The depolymerase gene fragment was obtained by PCR and cloned into the pET28a expression vector, and the expression and purification of the depolymerase were completed in strain BL21. The depolymerase activities on the capsular polysaccharide of serotype K1-type hvKp clinical isolates were detected by plaque assay and low-speed centrifugation assay. Results: A lytic phage (phiA2) that infected serotype K1-type hvKp clinical isolate was isolated from hospital sewage. It was typical of the Caudovirales order and Autographiviridae family, and its whole genome was 43 526 bp in length and contained 51 coding domain sequences. The phage phiA2-derived depolymerase phiA2-dep was predicted, expressed and purified. The plaque assay and low-speed centrifugation assay indicated that the depolymerase phiA2-dep had good lytic activity on the capsular polysaccharide of serotype K1-type hvKp clinical isolates. Conclusion: Depolymerase phiA2-dep can specifically degrade the capsular polysaccharide of serotype K1-type hvKp, which has potential application value in treating bacterial infection.

[Update on Tolvaptan for the Treatment of Refractory Ascites in Liver Cirrhosis].

Ascites is the most prevalent complication of decompensated cirrhosis, and approximately 5%-10% of cirrhotic ascites will develop into refractory ascites (RA). With complicated pathogenesis, obscure treatment strategies and poor prognosis, it is still a challenge for physicians to manage RA properly. Tolvaptan (TLV) is a new type of non-peptide selective arginine vasopressin V2 receptor antagonist targeting at suppressing renal water reabsorption, promoting free water excretion and raising blood sodium levels, which provides a new option for the treatment of RA in liver cirrhosis. In this review, we summarized the mechanisms of TLV's effect and described its efficacy, safety and predictive factors of response in treating RA, intending to provide a supplement for clinical application of tolvaptan in the management of RA.

[A multicenter retrospective study discussion on maintenance treatment strategies for mantle cell lymphoma].

Objective: This study aims to explore the survival advantages of different maintenance strategies for MCL. Methods: Clinical data of 693 newly diagnosed MCL patients in multi-centers admitted from April 1999 to December 2019 were collected. 309 cases received maintenance treatment. The characteristics of patients in different maintenance treatment groups were summarized and Kaplan-Meier survival and prognosis analysis were conducted. Results: The overall 3-year and 5-year progression-free survival (PFS) rates were (73.5±2.9) % and (53.6±4.3) %, respectively. The 3-year and 5-year overall survival (OS) rates were (94.2±1.5) % and (82.7±3.2) %, respectively. The clinical features of different maintenance treatment groups were generally consistent. The 3-year PFS rates of rituximab maintenance, lenalidomide maintenance, BTK inhibitor maintenance and dual-drug maintenance were (70.4±4.1) %, (69.1±7.6) %, (86.9±5.0) %, and (80.4±5.1) %, respectively. Corresponding 3-year OS rates were (92.9±2.4) %, (97.3±2.7) %, (97.9±2.1) %, and (95.3±2.7) %, respectively. There were no significant difference in different groups (P=0.632, 0.313). Survival analysis identified the MCL International Prognostic Index (MIPI) high-risk group and achieving complete remission before maintenance treatment as independent risk factors for PFS. The MIPI high-risk group, high-dose cytarabine application, treatment lines, and early disease progression (POD24) emerged as independent risk factors for OS. Conclusion: Comparing the different maintenance strategies of MCL, the result showed that BTK inhibitors (BTKi) maintenance demonstrated preliminary advantages in survival. Meanwhile, high-risk group according to MIPI and incomplete remission before maintenance treatment were significant factors related to disease progression.

[Five-year survival analysis of gastric cancer from population-based cancer registration data in Zhejiang province, China].

Objective: To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration. Methods: The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed. Results: 51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively. Conclusion: The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.