Background Polycyclic aromatic hydrocarbons (PAHs) are widely known atmospheric pollutants, which can cause serious harm to human body and ecological environment. Objective To analyze the concentrations and sources of PAHs in atmospheric PM_2.5 in Zhifu District and Longkou City during the heating period in Yantai. Methods Two monitoring sites in Zhifu District and Longkou City of Yantai were selected, and PM_2.5 sample collection was carried out from April 2023 to March 2024. Gas chromatography-mass spectrometry was applied to analyze the concentrations of PAHs in atmospheric PM_2.5 during the heating period (from November 2023 to March 2024) and the non-heating period (from April to October 2023). The concentrations of PAHs in the two periods were compared and the sources of PAHs during the heating period were analyzed by characteristic ratio method. Results During the heating period, the total concentration ranges of PAHs in atmospheric PM_2.5 at the monitoring sites in Zhifu District and Longkou City of Yantai were (1.59-23.70) ng·m⁻³ and (2.08-149.72) ng·m⁻³ respectively, and the medians (M) and the 25th and 75th percentiles (P₂₅, P₇₅) were 4.99 (2.61, 8.09) ng·m⁻³ and 15.46 (8.15, 29.05) ng·m⁻³ respectively. The PAHs concentrations in Longkou City were significantly higher than those in Zhifu District in all months (P<0.05). The highest median total concentrations of PAHs in both sites were reported in January (8.14 ng·m⁻³ and 81.56 ng·m⁻³ respectively). In the non-heating period, the M (P₂₅, P₇₅) of the total PAHs concentrations at the two sites were 1.59 (1.59, 2.78) ng·m⁻³ and 4.11 (2.94, 7.97) ng·m⁻³ respectively, much lower than those in the heating period (P<0.01). The order of composition of PAHs by ring number in PM_2.5 at both sites was 4-ring> 5-ring> 6-ring, with the 4-ring contributing the largest proportion (65.33% and 46.39% respectively). Fluoranthene had the highest concentration among PAHs at both sites, with concentrations M (P₂₅, P₇₅) of 1.29 (0.51, 1.78) ng·m⁻³ and 2.32 (1.30, 3.82) ng·m⁻³ respectively. The characteristic ratios of fluoranthene/(fluoranthene + pyrene), fluoranthene/pyrene, benzo[a]anthracene/(benzo[a]anthracene + chrysene), pyrene/benzo[a]pyrene, benzo[a]pyrene/(benzo[a]pyrene + chrysene), benzo[a]pyrene/benzo[g,h,i]pyrene, and indeno[1,2,3-c,d]pyrene/(indeno[1,2,3-c,d]pyrene + benzo[g,h,i]pyrene) in Zhifu District were 0.62, 1.65, 0.41, 4.48, 0.50, 0.93 and 0.47 respectively, and those in Longkou were 0.57, 1.35, 0.40, 2.89, 0.29, 0.79 and 0.47 respectively. The results showed that PAHs pollutants were generated by combination of coal combustion, vehicle exhaust emissions and gasoline combustion. Conclusion During the heating period in Yantai area, the total concentration of PAHs in atmospheric PM_2.5 is significantly higher than that in the non-heating period. Among them, during the heating period, the pollution level in Longkou City is significantly higher than that in Zhifu District. The local PAHs may be sourced from mixed pollution, and the main sources include gasoline, and coal combustion and vehicle exhaust emissions.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To investigate the current status of off-label drug use(OLDU)management in tertiary hospitals of Guizhou province and to provide baseline evidence for developing a unified administration regulation for OLDU in Guizhou province.Methods In line with the relevant policies and regulations,a questionnaire including basic information about the person filling out the form,basic information about the hospitals,and information about OLDU was developed.The questionnaire was sent to 84 tertiary hospitals in Guizhou province through the Wenjuanxing.Results A total of 84 questionnaires were distributed and recovered,with a response rate of 100.00%.Of the 84 hospitals,77 had OLDU,of which 68(88.31%)had established a management system for OLDU.Among the 77 hospitals with OLDU,65(84.42%),42(54.55%),58(75.32%),36(46.75%),15(19.48%),and 21(27.27%)hospitals respectively,required approval from the Committee on Drug Administration and Pharmacotherapy before OLDU,restricted the qualifications of doctors prescribing OLDU,required informed consent from patients or their families before OLDU,recorded the matters and reasons in the medical records of patients treated with OLDU,followed up patients in their files and evaluated the reasonableness of the OLDU,and carried out special reviews for OLDU.Only 30(38.96%)hospitals have set up a catalogue of OLDUs,and 58(75.32%)hospitals have urgent needs to set up a unified provincial catalogue of OLDUs.Conclusion The pharmacy administration level of OLDU in tertiary hospitals of Guizhou province is relatively low,so there is an urgent need to establish a unified OLDU management system and medication catalog.

Osteoporosis (OP) is a prevalent metabolic bone disease with a complex pathogenesis that has not yet been fully elucidated. Recent studies have revealed that the Toll-like receptor 4 (TLR4) signaling pathway plays a significant role in the development and progression of OP. TLR4, a crucial immune receptor primarily expressed in immune cells, is involved in inflammatory responses and immune regulation. The TLR4 signaling pathway influences bone metabolism and remodeling through multiple mechanisms. Therefore, investigating the role of the TLR4 signaling pathway in OP is of great significance for its prevention and treatment. Research targeting the TLR4 signaling pathway provides novel insights and approaches for OP therapy. Future studies should further explore the mechanisms of the TLR4 signaling pathway, develop therapeutic agents that modulate this pathway, and validate their efficacy in OP through clinical trials, thereby offering more options for the clinical management of OP.

Objective:To evaluate the role of G-protein coupled receptor 37 (GPR37) in cognitive dysfunction in a mouse model of neuropathic pain.Methods:SPF-grade healthy male C57BL/6 mice and GPR37 knockout (GPR37-KO) mice, aged 3 months, with a body weight of approximately 20 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (Con group), neuropathic pain group (NPP group), GPR37-KO+ control group (GPR37-KO Con group) and GPR37-KO+ neuropathic pain group (GPR37-KO NPP group). The mouse model of neuropathic pain was established by ligation of the sciatic nerve. The thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 7 days after surgery. The open field test and Morris water maze test were performed at 28 days after surgery. The mice were subsequently sacrificed, and the medial prefrontal cortex (mPFC) was obtained for determination of the level of phosphorylated calcium/calmodulin-dependent protein kinase Ⅱ(p-CAMKⅡ) and expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95). Results:Compared to Con group, no significant changes were found in the parameters in GPR37-KO Con group ( P>0.05), and TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in NPP group ( P<0.05). Compared with NPP group, TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in GPR37-KO NPP group ( P<0.05). Conclusions:GPR37 is involved in the development of cognitive dysfunction in mice with neuropathic pain, and the mechanism may be related to its modulation of synaptic plasticity.

Objective:To compare the setup errors in the supraclavicular regions of two different postures (arms placed on each side of the body, namely the body side group; arms crossed and elbows placed above forehead, namely the uplifted group) using the chest and abdomen flat frame fixation device in lung and esophageal cancer.Methods:Clinical data of patients with stage Ⅰ to Ⅳ lung or esophageal cancer who received three-dimensional radiotherapy with chest and abdomen flat frame fixation device in our institution from November 2020 to April 2021 were retrospectively analyzed. The setup errors of two postures were compared.Results:A total of 56 patients were included, including 31 patients (55%) in the body side group and 25 patients (45%) in the uplifted group. A total of 424 CBCTs were performed in the whole group. The overall setup errors in the X, Y and Z directions were similar in both groups ( P>0.05). The setup errors of sternoclavicular joint in the X and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.163±0.120) cm vs. (0.209 ±0.152) cm, P=0.033; 0.715°±0.628° vs. 0.910°±0.753°, P=0.011]. The setup errors of acromioclavicular joint in the Y, Z and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.233±0.135) cm vs. (0.284±0.193) cm, P=0.033; (0.202±0.140) cm vs. (0.252±0.173) cm, P=0.005; 0.671°±0.639° vs. 0.885°±0.822°, P=0.023]. The margins of target volume for setup errors were smaller in the X (0.45 cm vs. 0.54 cm) and Y (0.54 cm vs. 0.65 cm) directions of the sternoclavicular joint, as well as in the Y (0.59 cm vs. 0.78 cm) and Z directions (0.53 cm vs. 0.72 cm) of the acromioclavicular joint in the body side group. Conclusions:For lung and esophageal cancer patients requiring supraclavicular irradiation, the body side group yields smaller setup errors and corresponding margins of target volume than the uplifted group. In clinical practice, it is necessary to take comprehensive consideration of the accuracy of radiotherapy and additional radiation of the limbs to select appropriate posture.

Objective:To identify the biotypes of blood culture positive Brucella in patients with acute brucellosis in Xinjiang Uygur Autonomous Region (hereinafter referred to as Xinjiang), and to learn about the clinical characteristics of these patients. Methods:Among the 30 patients diagnosed with acute brucellosis in First Affiliated Hospital, School of Medicine, Shihezi University from January 2019 to July 2021, the positive strains of blood culture Brucella of 12 patients with acute brucellosis were used to identify the biotype by AMOS-PCR. Then the general and clinical data of the 12 patients were collected, including demographic characteristics, epidemiological characteristics, clinical characteristics, laboratory tests, treatment and prognosis. Results:AMOS-PCR results showed that all 12 strains were Brucella melitensis. Among the 12 patients, 9 were males and 3 were females, all of whom had a clear history of livestock contact, and the onset time was concentrated in April to September. All 12 patients showed fever, followed by headache and dizziness (9/12), weakness (8/12), digestive symptoms (8/12), hyperhidrosis (7/12), lumbago and backache (6/12), and arthralgia (6/12). One patient was complicated with pleural effusion and pericardial effusion. One patient was complicated with pleural effusion, pelvic effusion and ascites. Only ascites occurred in 2 patients. Liver function was abnormal in 3 patients, lactate dehydrogenase increased in 6 patients, and blood creatinine decreased in 9 patients. Among the 12 patients, 10 patients were treated with rifampicin combined with doxycycline. The other 2 patients were treated with levofloxacin and doxycycline, supplemented by symptomatic treatment with hepatoprotective drugs due to impaired liver function. After discharge, the patients received out-of-hospital oral anti-infectious drugs for 1-2 courses (6 weeks each course), and all indicators returned to normal at 6 months and 12 months after discharge. Conclusions:All the 12 patients with acute brucellosis in Xinjiang are infected with Brucella melitensis. In addition to the common clinical features, patients are characterized by decreased creatinine and increased lactate dehydrogenase. The standardized anti- Brucella treatment is still the main treatment strategy.

Objective:To investigate the immune response characteristics of helper T cells Th1, Th2, Th17 and their related cytokines in acute, chronic and recovery phases after Brucella infection. Methods:Using prospective study, a total of 130 patients with brucellosis in the First Affiliated Hospital of Medical College of Shihezi University from January 2017 to December 2018 were selected as the research subjects, including acute phase group (49 cases), chronic phase group (44 cases), recovery phase group (37 cases), and 30 cases of healthy physical examination during the same period were included in the control group. The peripheral blood samples of all subjects were collected, and flow cytometry was used to detect Th1, Th2 and Th17 cells in the peripheral blood; the cytometry bead array (CBA) was used to detect the serum cytokines interferon-γ (IFN-γ), interleukin (IL)-4 and IL-17A expression levels.Results:In the control, acute phase, chronic phase and recovery phase groups, the differences of the expression ratios of Th1 [(1.03 ± 0.85)%, (5.46 ± 3.54)%, (4.48 ± 2.26)%, (2.29 ± 2.25)%], Th2 [(4.72 ± 2.36)%, (7.00 ± 3.14)%, (13.99 ± 9.14)%, (5.89 ± 4.69)%], and Th17 cells [(2.09 ± 0.48)%, (3.04 ± 2.17)%, (3.61 ± 2.67)%, (2.74 ± 2.58)%] were statistically significant ( F = 20.95, 21.15, 2.90, P < 0.05). Compared with the control group, the expressions ratio of Th1, Th2, Th17 cells in acute and chronic phase groups and Th1 cells in recovery phase group were significantly higher ( P < 0.05); compared with the recovery phase group, the expressions ratio of Th1, Th2 and Th17 cells in acute and chronic phase groups were significantly higher, but the expression ratio of Th2 cells in acute phase group was lower than that in chronic phase group ( P < 0.05). The expression levels of IFN-γ, IL-4, and IL-17A in serum of control group, acute phase, chronic phase and recovery phase groups were significantly different ( F = 7.79, 15.85, 7.55, P < 0.05); compared with the control group, the expression levels of IFN-γ, IL-4, IL-17A in acute and chronic phase groups and IFN-γ, IL-4 in recovery phase group were significantly higher ( P < 0.05); compared with the recovery phase group, the expression levels of IFN-γ, IL-4, IL-17A in acute phase group and IFN-γ, IL-17A in chronic phase group were significantly higher ( P < 0.05). The expression ratio of Th1 cells in recovery phase patients who finished treatment for less than 12 months was significantly higher than that of recovery phase patients who finished treatment for ≥12 months ( t = 2.26, P < 0.05). Conclusions:After patients are infected with Brucella, Th1 cell immunity is dominant in acute phase, Th2 cell immunity is dominant in chronic phase, and there is no significant difference in the response of Th17 cell immunity between acute and chronic phases. The immune function of patients in the recovery phase may still be abnormal when the treatment time is less than 12 months. Some clinically cured patients in the recovery phase still have a relatively high proportion of Th1 cells, suggesting that the patient's immune function has not fully recovered.

Objective: To investigate the anti-tumor effect of CTL cells on colon cancer xenograft in nude mice after knocking out the immune check point CTLA-4 by CRISPR/Cas9 technology. Methods: A specific small guide RNA (sgRNA) for CTLA-4 was designed to construct sgRNA/Cas9 plasmid, which was then transfected into CTL using a lentiviral vector to obtain CTL cells with CTLA-4 deletion (CTLA-4 KO CTL). The transfection efficiency of the plasmid and the deletion efficiency of CTLA-4 were verified. BALB/c nude mice were randomly divided into two groups to prophylactically inoculate CTLA-4 KO CTL (experimental group) or CTL (control group); 3 days later, the animals of two groups were inoculated with colon cancer cell line LS174-T to observe the tumor formation rate and tumor formation time. After constructing colon cancer xenograft model in nude mice, the animals were randomly divided into two groups, respectively treated with CTLA-4 KO CTL (experimental group) and CTL (control group) cells to observe the tumor growth volume and survival time of mice. The serum levels of TNF-α and IFN-γ in nude mice were detected. Results: sgRNAwas designed and CRSIPR/Cas9 system with lentivirus as vector was successfully constructed. CTL cells were transfected with the established CRSIPR/ Cas9 system, and the highest transfection efficiency was up to (28.80±0.62)%. After transfection, the deletion efficiency of CTLA-4 was detected by Flow cytometry. The CTLA-4 expression of CTLA-4 KO CTL group was significantly lower than that of CTL group [(0.91±0.25)% vs (42.70±2.72)%, P<0.05]. In prophylactic assay, the formation rate of colon cancer xenografts in the experimental group was significantly lower than that in the control group(33.33%vs100%,P<0.05). In treatment assay, the tumor volume in the experimental group was significantly inhibited compared with the control group ([503±23.9] vs [911.2±51.4] mm3, P<0.05), and the survivaltimeoftheexperimentalgroupwassignificantlyprolonged (mediansurvivaltime:78dvs42d,P<0.05); Moreover, the secretion levels of serumTNF-α([268.93±17.04]pg/mlvs[148.26±20.07]pg/ml,P<0.05) and IFN-γ(315.38±18.67 pg/ml vs 202.92±29.32 pg/ml, P<0.05) in the experimental group were significantly higher than those in the control group. Conclusions: The lentiviral vector CRSIPR/Cas9 system is an effective gene editing method; its successful deletion of CTLA-4 in CTL cells can significantly inhibit the tumor formation rate of colon cancer xenografts in nude mice and enhance the anti-tumor effect of CTLon colon cancer xenografts.