Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

Functional neuroendocrine neoplasm, which secrete hormones and lead to diverse clinical symptoms, pose significant challenges in diagnosis and treatment. Early identification and standardized management are crucial for improving patient prognosis. This article summarized three clinically relatively common cases of Functional pancreatic neuroendocrine neoplasm (F-pNENs), focusing on analyzing their diagnostic key points and standardized therapeutic pathways. It aimed to provide reference for early clinical identification of rare tumors and improvement of standardized multidisciplinary diagnosis and treatment as well as personalized treatment strategies.

Objective Based on gender differences,this paper discusses the characteristics of facial color diagnosis in male and female patients with metaplastic chronic atrophic gastritis(CAG),and explores the pathological mechanism of different gender patients from the perspective of TCM pathogenesis,so as to provide personalized reference for TCM prevention and treatment of metaplastic CAG.Methods In this study,the complexion information of patients with chronic non atrophic gastritis(CNG)and CAG was collected by MT-BX-01 four-diagnostic instrument.The color colorimetric characteristics of male and female metaplastic CAG patients and CNG patients were analyzed by case-control study.Results In female patients,the L value and a value of liver region in CAG with mild intestinal metaplasia(IM)group,moderate and severe IM were significantly lower than those in CNG group(P<0.05).In male patients,the L value of spleen region in CAG with moderate and severe IM group was significantly higher than that in CNG group(P<0.05).Conclusion There is a certain gender difference in the facial color characteristics of patients with metaplastic CAG.The facial chromaticity value of female patients with metaplastic CAG changes most significantly in the liver area,while that of male patients mainly in the spleen area.It is suggested that the incidence of female metaplastic CAG is mostly related to liver,while that of male is mostly related to spleen,which provides a personalized method for clinical diagnosis and treatment of metaplastic CAG based on gender differences.

Objective To analyze the morphology of the pterygoid hamulus and its relationship with adjacent tissues on CBCT ima-ges,establish reference data of the anatomical structure of the pterygoid hamulus in the adult population,in order to provide a basis for clinical assisted diagnosis and treatment of pterygoid hamulus syndrome and obstructive sleep apnea hypopnea syndrome.Methods A total of 151 patients with CBCT images who met the inclusion criteria were collected from August 2020 to December 2023 in the Depart-ment of Stomatology at the Second Traditional Chinese Medicine Hospital of Jiangsu Province.The CBCT images were reconstructed u-sing the maximum intensity projection(MIP)and volume rendering(VR)modes of cone-beam CT.The morphology,length,width,vertical height,abduction angle,mucosal thickness,distance from the pterygoid hamulus to the midline of the palate,and distance from the pterygoid hamulus to the greater palatine foramen were observed and statistically analyzed in 302 bilateral cases.The differ-ences in the morphology of the pterygoid hamulus and its adjacent tissues were analyzed in different places,genders and age groups.Results The apex of the pterygoid hamulus faced inward on 6 sides and outward on 296 sides.The apex of the pterygoid hamulus was sharp on 46 sides and blunt on 256 sides.The pterygoid hamulus showed no statistically significant differences in various parameters be-tween the left and right sides,except for the width.In males,the length,width,height,distance from the pterygoid hamulus to the mid-palatal suture,and mucosal thickness on the surface of the hamulus were all greater than those in females,demonstrating statisti-cally significant differences.Females also exhibited a larger outward angle of the pterygoid hamulus than males,which was statistically significant.Moreover,with the increase of age,the length and height of the pterygoid hamulus initially increased and then decreased,exhibiting statistically significant differences.Conclusion CBCT has the advantages of low radiation dosage,convenient operation,clear imaging,stable measurement data,and clear images in the examination of pterygoid hamulus.It helps in the diagnosis and treat-ment of pterygoid hamulus-related diseases in a clinical setting.

Objective:To explore the application effect of ultrasound evaluation of atelectasis in general anesthesia.Methods:Eighty patients who underwent general anesthesia surgery at the Second Affiliated Hospital of Wannan Medical College from January 2019 to December 2020 were selected as the study subjects. The gold standard was chest CT diagnosis of perioperative atelectasis, and they were divided into atelectasis group (39 cases) and control group (41 cases). Twelve regional images, including left upper anterior chest, left lower anterior chest, right upper anterior chest, right lower anterior chest, left upper chest, left lower chest, right upper chest, right upper chest, right lower chest, right upper chest, right lower chest, right upper chest, right lower chest, right lower chest, right lower chest, left upper chest, right lower chest, left upper chest, right lower chest, left upper posterior region, left lower chest, left lower posterior region, left lower posterior region, right upper posterior region, and right lower posterior region, were collected by pulmonary ultrasound (LUS) at time points T 1 after entering the room, 30 minutes after tracheal intubation (T 2), 30 minutes after extubation (T 3), 24 hours after surgery (T 4), and 48 hours after surgery (T 5), And an improved semi quantitative scoring method for evaluating lung ventilation was used to compare the LUS scores of the two groups at 5 time points. Results:There was no statistically significant difference in LUS scores between the two groups of patients in different lung zones at T 1 (all P>0.05); There are varying degrees of differences in LUS scores for the same lung partition at different times (all P<0.05). There was no statistically significant difference in LUS scores between T 2 and T 5 for left upper anterior chest, left lower anterior chest, right upper anterior chest, left upper chest, right upper chest, left upper posterior region, and right upper posterior region (all P>0.05); The LUS scores of the T 2-T 5 atelectasis group in the lower left chest, lower right chest, lower left posterior area, and lower right posterior area were higher than those of the control group (all P<0.05). Conclusions:LUS can be used to evaluate atelectasis during general anesthesia and has broad clinical application and promotion value.

OBJECTIVE To compare the similarities and differences of the two methods in analyzing the use of opioids in third grade class A medical institutions and provide a reference for the management of opioids in medical institutions. METHODS Two methods， Defined Daily Dose （DDD） and Oral Morphine Equivalent （OME）， were used to count the opioid prescription data of five comprehensive medical institutions of third grade class A （named H1-H5） in Shanxi province in 2020， calculate consumption sum of opioid， annual per capita consumption sum， patient cost burden and drug consumption sum ratio， compare the index results presented by the two analysis methods， and explore the application scenarios of the advantages of each of the two evaluation methods. RESULTS The ranking of consumption sum of opioid and patient cost burden calculated by the two methods was the same in the five sample medical institutions， but the ranking of per capita consumption sum was different. Taking the 5 medical institutions as a whole， the top 4 rankings of consumption sum ratio for each species of opioid compared by both methods were the same， i. e. remifentanil＞sufentanil＞oxycodone＞morphine. The ratio of remifentanil was close to 50%. When comparing the ranking of consumption sum ratio in each medical institution， the ranking calculated by the two methods was different for those medical institutions except for H1 medical institutions. The consumption sum ratio of fentanyl calculated by DDD method was significantly higher than that of OME method； whereas consumption sum ratio of remifentanil calculated by OME method was significantly higher than that of DDD method. Perioperative patients had the highest consumption sum ratio， about 50%. The consumption sum ratio of critically ill patients in H3 jwsydey@163.com medical institutions and inpatient patients with cancer pain and other patients in H5 medical institutions calculated by DDD method was significantly higher than that by OME method. There were differences in the order of cost burden of different types of patients calculated by two methods. CONCLUSIONS DDD method can accurately reflect the dosage of opioid drugs and facilitate the monitoring and management of the dosage； OME method can more reflect the analgesic effect and compare the cost burden of patients.

Objective:To observe the prevention and control effect of 1% atropine on the progression of form deprivation myopia (FDM) in guinea pigs and the potential biological mechanism.Methods:Sixty-nine 3-week-old tricolor guinea pigs with normal refraction were randomly divided into a normal control group ( n=19), a FDM group ( n=19), a FDM+ atropine group ( n=19), and an atropine group ( n=12). No intervention was given to guinea pigs in normal control group.The FDM model was established by covering the right eye of guinea pigs with a semitransparent latex facemask for 4 weeks in FDM and FDM+ atropine groups.For the FDM+ atropine group, 1% atropine gel was topically administered to the form-deprived right eyes once a day for 4 weeks.For the atropine group, the right eye was treated with 1% atropine gel once a day for 4 weeks.Refraction and axial length of guinea pigs were measured by retinoscopy and ophthalmic A-scan ultrasonography respectively at baseline, experiment week 2 and week 4.In experiment week 4, eyeballs were enucleated to make sections via the paraffin wax processing procedure, and the microstructural and ultrastructural changes of the sclera were observed under the light microscope and transmission electron microscope, respectively.The isobaric tags for relative and absolute quantitation labeling combined with liquid chromatography-tandem mass spectrometry were used to identify the differentially expressed proteins.Use and care of the animals complied with the Regulation for the Administration of Affairs Concerning Experiment Animals by State Science and Technology Commission.The study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.TJYY2020111028). Results:There were statistically significant differences in the diopter of guinea pigs at different time points among the four groups ( Fgroup=138.892, P<0.001; Ftime=167.270, P<0.001). Compared with normal control group, the diopter of guinea pigs in FDM group at experiment weeks 2 and 4, and FDM+ atropine group at experiment week 4 developed toward myopia, showing statistically significant differences (all at P<0.001). Compared with FDM group, the diopter of guinea pigs in FDM+ atropine group at experiment weeks 2 and 4 developed toward hyperopia, showing statistically significant differences (both at P<0.001). There were statistically significant differences in the axial length of guinea pigs at different time points among the four groups ( Fgroup=32.346, P<0.001; Ftime=353.797, P<0.001). The axial lengths of FDM group at experiment weeks 2 and 4 and FDM+ atropine group at experiment week 4 were longer than those of normal control group, and the axial lengths in FDM+ atropine group at experiment weeks 2 and 4 were shorter than those in FDM group, and the differences were statistically significant (all at P<0.001). The collagenous fibers of posterior sclera of guinea pigs were loose and disordered in FDM group, and were regular in FDM+ atropine group.The posterior scleral thickness of normal control group, FDM group, FDM+ atropine group and atropine group was (141.74±16.98), (101.46±9.15), (112.74±6.24) and (134.30±18.19) μm, respectively, with a statistically significant difference ( F=6.709, P=0.005). The posterior sclera was significantly thinner in FDM group than in normal control group and FDM+ atropine group (both at P<0.05). The diameter of posterior scleral collagen fiber gradually increased from inside to outside in normal control group, FDM+ atropine group and atropine group, and the diameters of the inner, middle and outer posterior scleral collagen fibers were smaller in FDM group than in normal control group.Proteomic analysis revealed 85 differentially expressed proteins (fold change>1.30) between FDM group and normal control group, FDM+ atropine group and FDM group, of which 38 were up-regulated and 47 were down-regulated after atropine treatment.Gene Ontology enrichment analysis showed that biological processes mainly involved were biological regulation, cell process, localization and metabolic process.Molecular function mainly involved were binding, catalytic activity, molecular function regulator, structural molecule activity and transporter activity.Cell components mainly involved were in cellular anatomical entity, intracellular and protein-containing complex. Conclusions:Atropine can increase the diameter of scleral collagen fibers in guinea pigs of FDM model, improve the arrangement of scleral collagen fiber, inhibit scleral thinning.The mechanism of atropine to control myopia progression is closely related to the tight junction between scleral cells, cytoskeleton and extracellular matrix remodeling.

Objective:To noninvasively evaluate the clinical value of early renal function changes in patients with type 2 diabetes mellitus (T2DM) using blood oxygenation level dependent (BOLD) and arterial spin labeling (ASL) MRI.Methods:A total of 63 T2DM patients from Tianjin First Central Hospital from September 2019 to May 2022 were prospectively collected, 30 healthy volunteers (control group) were collected during the same period. According to albumin creatinine ratio (ACR), patients with T2DM were divided into normal albuminuria (NAU, ACR<30 mg/g) group and microalbuminuria (MAU, 30 mg/g≤ACR≤300 mg/g) group, there were 35 and 28 cases respectively. All subjects underwent abdominal BOLD and ASL scans. The values of renal cortical and medullary apparent relaxation rate (R 2*) and renal cortical renal blood flow (RBF) were measured. One-way ANOVA was used to compare the differences in R 2* and RBF among the three groups. Receiver operating characteristic curve was used to analyze relevant parameters to identify the diagnostic effectiveness of each group, and area under the curve (AUC) was compared by Z-test. Results:There were significant differences in renal medullary R 2* and renal cortical RBF among the control group, NAU group and MAU group ( F=45.83, 34.15, P<0.001). There was no significant difference in renal cortical R 2* ( F=2.98, P=0.056). In differentiating the control group from the NAU group, the AUC of renal medullary R 2*, renal cortical RBF and their combined parameters were 0.921 (95%CI 0.827-0.973), 0.704 (95%CI 0.578-0.811), 0.964 (95%CI 0.885-0.994), respectively. The AUC of combined parameters was significantly different from renal cortical RBF ( Z=4.07, P<0.001), but not from renal medullary R 2* ( Z=1.57, P=0.117). In differentiating the NAU from the MAU group, the AUC were 0.898 (95%CI 0.796-0.960), 0.919 (95%CI 0.823-0.973), 0.985 (95%CI 0.881-0.994), respectively. The AUC of combined parameters was significantly different from renal medullary R 2* and renal cortical RBF ( Z=2.39, P=0.017; Z=2.20, P=0.028). Conclusions:The changes of renal oxygenation level and blood flow in early stage of T2DM patients can be evaluated noninvasively and quantitatively using BOLD and ASL. Renal medullary R 2* combined with renal cortex RBF shows better diagnostic efficacy for early renal function changes in diabetes than each single index.

Objective To investigate the effect of hyponatremia on the survival of cancer patients treated with camrelizumab.Methods The clinical and follow-up data of 100 patients treated with camrelizumab for the first time in Zhongshan Hospital,Fudan University from May 2019 to May 2020 were collected retrospectively,and the patients were divided into hyponatremia group and normal blood sodium group according to the blood sodium level at baseline before immunotherapy.Chi-square test was used to compare categorical variables between the two groups.Kaplan-Meier method with log-rank test was used to analyze survival of patients.Cox regression analysis was conducted to evaluate the impact of hyponatremia on prognosis.Results There were no statistically significant differences in gender,age,body mass index,Eastern Cooperative Oncology Group performance status(ECOG PS)score,nutritional risk screening 2002(NRS2002)score,tumor site,TNM stage,metastasis site number,and concurrent medication between the two groups.The median overall survival in the hyponatremia group and the normal sodium group was 3.9 months(95%CI 2.864-5.136)and 14.967 months(95%CI 6.840-23.093),respectively(P＜0.05);the median progression-free survival in the hyponatremia group and the normal sodium group was 2.933 months(95%CI 2.420-3.447)and 7.0 months(95%CI 4.103-9.897),respectively(P＜0.05).After adjusting for primary tumor,statistically differences were also observed in both overall survival and progression-free survival between the two groups(P＜0.05).The multivariate Cox analysis showed that both the death and disease progression risks of patients with hyponatremia increased(P＜0.05).After adjusting for age,gender,primary tumor site,and TNM staging,the blood sodium level remained independent influences on both overall survival and progression-free survival of patients(P＜0.05).Conclusion Baseline hyponatremia may be associated with the prognosis of patients with malignant tumors treated with camrelizumab,and further validation is warranted through large-scale prospective studies.

OBJECTIVE: To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak. METHODS: A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed. RESULTS: A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak. CONCLUSION TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.
COVID-19/virology* ; Genome, Viral ; Humans ; Mutation ; SARS-CoV-2/genetics*