The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

An etiological analysis of a diarrhea outbreak attributed to C.perfringens was conducted.Anal swab and envi-ronmental smear samples were collected and subjected to fluorescence PCR detection of C.perfringens plc and cpe,as well as isolation and culture of C.perfringens before and after enrichment culture.The isolated colonies underwent fully automated bi-ochemical identification and time-of-flight mass spectrometry analysis.Whole genome sequencing of isolates identified as C.perfringens was performed to analyze the strain carrying virulence and resistance genes,and the genetic aggregation based on single nucleotide polymorphisms in the core genome for all isolates.The positivity rates for plc and cpe genes without bacterial enhancement were 46.15％(6/13)and 53.85％(7/13),respectively.The positivity rates for plc and cpe genes after 24 h anae-robic bacterial enhancement in BHI were 38.46％(5/13)and 53.85％(7/13).All ten isolated CP belonged to the F biotype,with virulence gene characteristics of plc+/cpb-/etx-/iA-/cpe+/cpb2+/netB-.The phylogenomic tree indicated that all ten case-patient isolates except P1 isolate(lineage 1)were closely related and clustered together in a single clade(lineage 2).Lineage 1 belonged to ST589 and carried the macrolide re-sistance gene erm(Q),whereas lineage 2 belonged to ST149 and carried the tetracycline resistance gene tetB(P).The outbreak was caused by type F C.perfringens,and most ca-ses were infected with a group of highly clonogenic cpe+col-onies.Whole genome sequencing technology can be applied to etiology analysis of C.perfringens outbreak events,and the enrichment culture and molecular screening methods for C.per-fringens based on anal swab samples should be further developed and applied.

Cervical cancer, the most common gynecological malignancy, significantly and adversely affects women's physical health and well-being. Traditional surgical interventions and chemotherapy, while potentially effective, often entail serious side effects that have led to an urgent need for novel therapeutic methods. Photothermal therapy (PTT) has emerged as a promising approach due to its ability to minimize damage to healthy tissue. Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects. In this study, we developed a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe, S-NBD, which demonstrated robust PTT performance. This innovative probe is capable of activating NIRF/PA signals to enable the detection of biothiols with high emission wavelength (838 nm) and large Stokes shift (178 nm), allowing for in vivo monitoring of cancer cells. Additionally, the probe achieved an outstanding photothermal conversion efficiency of 67.1%. The application of laser irradiation (660 nm, 1.0 W/cm², 5 min) was able to achieve complete tumor ablation without recurrence. In summary, this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging, incorporating features from PTT for the first time. This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

ObjectiveTo establish a more accurate and sensitive liquid chromatography-ultraviolet (LC-UV) method for the determination of uric acid in rat serum, and compare the results with those of commercial kits, providing a new method for the accurate determination of uric acid in the rat hyperuricemia model induced by potassium oxonate.Methods A hyperuricemia model was established by intraperitoneal injection of potassium oxonate (300 mg/kg) into SPF-grade male SD rats, and the control group was administered an equal amount of 0.5% sodium carboxymethylcellulose solution. Blood samples were collected from the posterior orbital venous plexus and centrifuged to obtain serum samples. After precipitation with 0.1% trifluoroacetic acid-acetonitrile (containing the internal standard 3,4-dihydroxybenzylamine hydrobromide), the supernatant was injected for analysis. Uric acid was separated on a Waters XBridge HILIC column (150 mm×4.6 mm, 3.5 μm) using acetonitrile (containing 0.5% formic acid and 2 mmol/mL ammonium formate) as the organic phase and methanol solution (methanol∶water=1∶1, containing 0.5% formic acid with 2 mmol/L ammonium formate) as the aqueous phase for isocratic elution and detection at 290 nm. Serum samples treated with activated carbon were used as substitute matrices for the methodological verification. Serum uric acid levels in rats with potassium oxonate-induced hyperuricemia were measured using the established LC-UV method and commercially available kits (uricase and phosphotungstic acid methods), and the accuracies of the three methods were compared.Results Serum uric acid showed a good linear relationship (R>0.999) at mass concentration of 10–200 μg/mL in rats, the lower limit of quantification was 10 μg/mL, the accuracy ranged from -2.17% to 2.21%, the intra-batch precision ranged from 0.52% to 1.95%, the inter-batch precision ranged from 3.04% to 4.90%, and the extraction recovery ranged from 83.12% to 89.91%. In the rat model, the results obtained using the commercially available phosphotungstic acid method kit were significantly higher than those of the LC-UV method, and those obtained using the commercially available uricase method kit were significantly lower than those of the LC-UV method, but the LC-UV method showed the best recovery of the spiked sample (95.90%–99.96%).ConclusionThe LC-UV method developed in this study can determine the concentration of uric acid in rat serum with higher accuracy than commercially available kits and is recommended for the determination of serum uric acid in the rat model of hyperuricemia induced by potassium oxonate.

Objective:To explore the mediating role of self-control in the relationship between alexithymia and internet addiction.Methods:From August to September 2019, a total of 433 college students were selected from three universities in Jiangxi province by cluster random sampling method. The Chinese internet addiction scale-revised, the twenty-item Toronto alexithymia scale and brief self-control scale were used for questionnaire testing. SPSS 23.0 software was used for descriptive statistics, Pearson correlation analysis and PROCESS V3.5 macro program was used to test the mediating effect.Results:The total scores of alexithymia, internet addiction and self-control were (53.61±9.44), (45.31±9.84) and (41.91±6.09), respectively. Pearson correlation analysis showed that alexithymia was significantly positively correlated with internet addiction ( r=0.47, P<0.01), and significantly negatively correlated with self-control ( r=-0.37, P<0.01). The negative correlation between self-control and internet addiction was significant ( r=-0.46, P<0.01). Multivariate hierarchical regression analysis showed that alexithymia directly predicted internet addiction after controlling the influence of gender. Self-control played a partially mediating role in the relationship between alexithymia and internet addiction (effect size=0.13, 95% CI: 0.082-0.185), the mediating effect accounted for 25% of the total effect. Conclusion:Alexithymia not only directly affects college students′ internet addiction, but also indirectly affects college students′ internet addiction through self-control.

Objective:To investigate the use of discriminant analysis to predict the risk of nosocomial mortality in patients with traumatic hemorrhagic shock.Methods:The clinical data of 238 patients with traumatic hemorrhagic shock admitted to Peking University People's Hospital from Sep 2013 to Aug 2020 were retrospectively analyzed. Patients were divided into survival group (214 cases) and death group (24 cases). Stepwise discriminant analysis was used to establish a discriminant model.Results:The difference of history of stroke (9.8% vs. 25.0%), main site of bleeding (extremities)(58.9% vs. 29.2%), APACHEⅡ score (16.4±5.1 vs. 23.2±6.1), blood lactic acid [2.1(1.1-3.5) mmol/L vs. 4.9(2.0-13.4) mmol/L] and surgery (92.5% vs. 58.3%) between the two groups was all statistically significant (all P<0.05). Finally, There are five indicators that entered the discriminant model: history of stroke, main site of bleeding (extremities), blood lactic acid, APACHE Ⅱ score and surgery. The area under the ROC curve for predicting the risk of mortality in patients with traumatic hemorrhagic shock was 0.857, 95% CI 0.754-0.959. Conclusions:The established discriminant model has a high accuracy in predicting the risk of in-hospital mortality in patients with traumatic hemorrhagic shock.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP). METHODS: With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals. RESULTS: Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals. CONCLUSION The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.
Brain/abnormalities* ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Female ; Humans ; Interferon Regulatory Factors/genetics* ; Mutation, Missense ; Pedigree ; Whole Exome Sequencing

Objective To investigate the application value of diameter change of superior rectal vein (SRV) and inferior mesenteric vein (IMV) by CT examination in the efficacy evaluation of neoadjuvant therapy for locally advanced rectal cancer.Methods The retrospective descriptive study was conducted.The clinicopathological data of 40 patients with locally advanced rectal carcer who underwent neoadjuvant therapy in the First Affiliated Hospital of Chongqing Medical University were collected.There were 28 males and 12 females,aged from 12 to 75 years,with the age of (55± 12)years.All patients underwent radical resection of rectal cancer according to the principle of total mesorectal resection after neoadjuvant therapy.Observation indicators:(1) MRI examination;(2) CT examination;(3) surgical situations;(4) follow-up.Follow-up was performed using outpatient examination to detect postoperative complications up to June 2019.The measurement data with normal distribution were represented as Mean±SD,and paired sample t test was used for intra-group comparison.Count data were described as absolute numbers or percentages.Results (1) MRI examination:there were 22 patients with positive extramural vascular invasion (EMVI) and 18 with negative EMVI.(2) CT examination:the diameter of SRV was (3.9 ± 0.9) mm and (3.0 ± 0.6) mm before and after neoadjuvant therapy,showing a significant difference (t=5.75,P＜0.05).Subgroup analysis:for the 30 patients with response to neoadjuvant therapy,the diameter of SRV changed significantly after neoadjuvant therapy [(4.1 ± 1.0) mm vs.(3.4±0.7) mm,t =6.20,P＜0.05];for the 10 patients without response to neoadjuvant therapy,the diameter of SRV showed no significant difference after neoadjuvant treatment [(3.6±0.6)mm vs.(3.5±0.8)mm,t=1.13,P＞0.05].The diameter of SRV was (4.2±0.8)mm in 22 patients with EMVI and (3.7±0.8)mm in 18 patients with negative EMVI,showing a significant difference between the two groups (t =2.45,P＜0.05).The diameter of IMV was (5.1 ± 0.9)mm and (4.2±0.9)mm before and after neoadjuvant therapy,showing a significant difference (t=4.16,P＜ 0.05).Subgroup analysis:for the 30 patients with response to neoadjuvant therapy,the diameter of IMV changed significantly after neoadjuvant treatment [(5.1 ± 0.9) mm vs (4.6± 0.8) mm,t =0.76,P＜ 0.05];for the 10 patients without response to neoadjuvant therapy,the diameter of SRV showed no significant difference after neoadjuvant treatment [(5.0±0.9)mm vs (4.8±1.0)mm,t=0.76,P＞0.05].The diameter of IMV was (4.8± 0.9) mm in 22 patients with EMVI and (4.6±0.8) mm in 18 patients with negative EMVI,showing no significant difference between the two groups (t =2.45,P＞ 0.05).(3) Surgical situations:40 patients underwent radical resection of rectal cancer,including 4 with synchronous liver metastases undergoing resection of metastases.(4) Follow-up:40 patients were followed up for 3.0-6.0 months,with a median follow-up time of 4.5 months.One of 40 patients with perineal incision infection was improved and discharged after dressing change,1 with anastomotic leakage on the 5th day after operation was improved and discharged after conservative treatment,1 of 2 with adhesive intestinal obstruction was improved after surgery and 1 was improved after conservative treatment,other 36 patients were discharged and no obvious abnormality occured during the follow-up.Conclusions The diameters of SRV and IMV in patients with locally advanced rectal cancer can be significantly decreased significantly after neoadjuvant therapy.The diameters of SRV and IMV can be used as potential indices to evaluate the effects of neoadjuvant therapy for rectal cancer,and the SRV had a higher evaluation value.

Objective To investigate the ultrasonic features of fetal isolated coronary artery fistula ( CAF) . Methods A total of 13 cases of fetal isolated CAF from December 2011 to M arch 2018 were retrospectively analyzed . Data of echocardiography and follow‐up were collected .All cases were divided into retrograde group and no retrograde group based on the presence of diastolic retrograde flow in aortic arch . T he inner diameters of affected coronary arteries ( CA ) and aortic annulus ( AO ) were measured ,and the CA to AO ratios ( CA/AO ) were then calculated .Correlations between CA ,CA/AO and the presence of retrograde flow were analyzed . Adverse birth outcomes including abortion , enlarged cardiac cavity , pulmonary hypertension were recorded at follow‐up . Correlation between diastolic retrograde flow in aortic arch and the rate of adverse birth outcomes was analyzed . Results ① T hirteen cases of fetal CAF were characterized by the varying degrees of dilation of affected coronary arteries . T hirteen cases were presented with abnormal blood flow in the large arteries or cardiac cavities :biphasic continuous flow pattern in atrio‐ coronary fistula and biphasic bidirectional continuous flow pattern with a diastolic dominant flow in coronary artery to ventricle fistula . Seven cases were presented with retrograde holodiastolic flow in aortic arch . ②T he CA/AO ratios of retrograde group was higher than in no retrograde group [ ( 0 .63 ± 0 .24 ) mm vs ( 0 .39 ± 0 .09) mm , P ＝0 .047] ,there was no significant difference of CA between the two groups [ ( 3 .00 ± 1 .25) mm vs ( 2 .03 ± 0 .62) mm , P ＝0 .115] . ③T he rate of adverse birth outcomes in retrograde group was higher than in no retrograde group ( 80% vs 20% ,χ2 ＝4 .80 , P ＝0 .028) . Conclusions Fetal isolated CAF has distinct ultrasonic features . Abnormal CA/AO ratio and diastolic retrograde flow in aortic arch are significant ultrasonic features and has prognostic values .