OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

ObjectiveTo analyze the measures and effects of comprehensive noise control in an automobile engine manufacturing enterprise. Methods An automobile engine manufacturing enterprise with noise exposure work-sites was selected as the research subject. The noise hazard status of the enterprise was investigated. The noise hazard exceeded the national standard in work-sites was comprehensively treated. The treatment effect was analyzed. Results A total of 395 work-sites exposed to noise were detected. Among them, 16 work-sites exceeded the national noise standard, with the rate of 4.1%. The work-sites with noise exceeding the national standard were mainly in the machine workshop and the casting workshop, with normalization of equivalent continuous A-weighted sound pressure level to a nominal eight hours working day (L_EX,8h) ranging from 86.8 to 89.2 and 85.2 to 90.2 dB(A), respectively. In addition, the classification of occupational noise exposure of the mold protection group in the casting workshop was level Ⅱ, and classification of occupational noise exposure of other work-sites with excessive national standard was grade Ⅰ. After the enterprise implemented noise control measures such as process reform, equipment replacement, sound insulation, noise reduction, sound absorption, and vibration isolation, the L_EX,8h of nine positions were lower than those before rectification ［(86.7±1.1) vs (83.3±1.3) dB(A), P<0.01］. Conclusion The use of comprehensive control measures can achieve the purpose of reducing noise from the sources, and can be used for reference by relevant enterprises with noise hazards.

Objective To observe the effects of methylenedioxygenase(TET2)expression on the proliferation ability,apoptosis rate,cell cycle,migration,and invasion of non-small cell lung cancer cells.Methods Detect the expression of TET2 gene and protein in different non-small cell lung cancer cells through RT-PCR and Western blot.Knock down the gene expression of the highest TET2 expressing cells(shRNA1)and overexpress the gene in the most low TET2 expressing cells(OE-TET2).Detect the effect of TET2 expression on cell proliferation through CCK-8,observe the effect of TET2 expression on cell apoptosis and cell cycle through flow cytometry,and observe the effect of TET2 expression on cell migration and invasion ability through migration and invasion experiments.Results The expression levels of TET2 gene and protein in H1299 cells were the highest,while A549 cells had the lowest expression levels(P＜0.05).The proliferation ability of OE-TET2 group cells was significantly lower than that of normal A549,while the proliferation ability of shRNA1 group cells was significantly higher than that of normal H1299 cells(P＜0.05).The apoptosis rate of OE-TET2 group was significantly higher than that of normal A549 cells,while the apoptosis rate of shRNA1 group was significantly lower than that of normal H1299 cells(P＜0.05).The number of migration and invasion cells in the OE-TET2 group was significantly lower than that of normal A549 cells,while the migration and invasion cells in the shRNA1 group were significantly higher than those in normal H1299 cells(P＜0.05).Conclusion TET2 can reduce the proliferation ability,increase its apoptosis rate,and slow down its migration and invasion ability of non-small cell lung cancer cells.

Objective:To investigate the predictive value of combined detection of serum microribonucleic acid-30c-5p(miR-30c-5p)and neuroligin-1(NLGN1)for postoperative recur-rence and metastasis in patients undergoing laparoscopic radical resection of colorectal cancer.Methods:A total of 112 colorectal cancer patients who underwent laparoscopic radical resection from August 2021 to August 2022 were regarded as the diseased group.They were separated into a recurrent group(n=28)and a non-recurrent group(n=84)based on whether the patients had recurrence or metastasis within 12 months after surgery.Additionally,92 normal volunteers who underwent physical examinations were as the control group.QRT-PCR was applied to de-tect serum miR-30c-5p and NLGN1 mRNA levels.Multivariate logistic regression was applied to analyze the affecting factors of postoperative recurrence and metastasis in patients.Receiver op-erating characteristic(ROC)curve was plotted to analyze the predictive value of serum miR-30c-5p and NLGN1 mRNA for postoperative recurrence and metastasis in patients.Pearson method was applied to analyze the correlation between miR-30c-5p and NLGN1.Results:The miR-30c-5p level in the diseased group was greatly lower than that in the control group(P＜0.05),and the NLGN1 mRNA level was significantly higher than that in the control group(P＜0.05).Compared with the non recurrent group,the miR-30c-5p level in the recurrent group was significantly re-duced(P＜0.05),while the NLGN1 mRNA level was significantly increased(P＜0.05).There was a statistically significant difference in tissue differentiation between the non-recurrent group and the recurrent group(P＜0.05).Low differentiation of tumor tissues and elevated level of NLGN1 mRNA were risk factors for postoperative recurrence and metastasis(P＜0.05).Elevated level of miR-30c-5p was a protective factor of postoperative recurrence and metastasis(P＜0.05).The AUC of serum miR-30c-5p,NLGN1 mRNA,and their combined prediction for postoperative re-currence and metasta sis in patients was 0.823,0.823,and 0.902,which was greatly better than the individual prediction of miR-30c-5p(Z=2.031,P=0.042)and NLGN1 mRNA(Z=2.239,P=0.025).There was a negative correlation between miR-30c-5p and NLGN1 mRNA levels(r=-0.436,P＜0.05).Conclusion:The dicrease of miR-30c-5p level and increase of NLGN1 mRNA level in laparoscopic colorectal cancer patient has auxiliary predictive value for postoperative recur-rence and metastasis.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To compare the efficacy on insomnia between Fang 's scalp acupuncture combined with conventional acupuncture and the simple conventional acupuncture. METHODS: A total of 66 patients with insomnia were randomly divided into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 2 cases dropped off). In the control group, the routine acupuncture therapy was applied to Shenmen (HT 7), Baihui (GV 20), Zhaohai (KI 6) and Sanyinjiao (SP 6), etc. Based on the treatment as the control group, Fang's scalp acupuncture therapy was supplemented at fuxiang tou, fuzang shangjiao, fuzang zhongjiao, siwei, etc. At these scalp points, the needles were inserted perpendicularly with flying needling technique and manipulated with trembling one. In either group, the treatment was given once daily, continuously for 2 weeks. Before and after treatment, separately, the score of Pittsburgh sleep quality index (PSQI) and the score of Chinese perceived stress scale (CPSS) were observed, as well as the parameters monitored by polysomnography, i.g. total sleep time (TST), sleep onset latency (SOL), wakefulness after the sleep onset (WASO), sleep efficiency (SE), the percentages of the time of rapid eye movement sleep phase (REM) and non-rapid eye movement sleep phase 1, 2, 3 and 4 in TST (REM%, N1%, N2%, N3%). The efficacy was compared between two groups. RESULTS: After treatment, the scores of each factor and the total scores of PSQI, as well as CPSS scores were all lower than those before treatment in the two groups (P<0.01, P<0.05); except the score for sleep quality, the score of each factor and the total score of PSQI, as well as CPSS score in the observation group were lower than those in the control group (P<0.01, P<0.05). After treatment, TST, SE%, REM% and N3% were increased and SOL, WASO, N1% were decreased as compared with before treatment in the two groups (P<0.01, P<0.05), and N2% in the observation group was decreased (P<0.01); SE%, REM% and N3% in the observation group were higher than the control group (P<0.05) and N1% and N2% were lower than the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, higher than 87.1% (27/31) in the control group (P<0.05). CONCLUSION Fang 's scalp acupuncture, on the base of routine acupuncture, obviously improves the sleep quality and perceived stress and adjusts the sleep structure in the patients with insomnia.
Acupuncture Points ; Acupuncture Therapy/methods* ; Humans ; Scalp ; Sleep ; Sleep Initiation and Maintenance Disorders/therapy* ; Stress, Psychological/therapy* ; Treatment Outcome

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

OBJECTIVE: To compare the clinical efficacy of staged surgery on Sanders Ⅳ calcaneal fractures with soft tissue Ⅲ swelling. METHODS: The clinical data of 76 patients with Sanders type Ⅳ closed calcaneal fracture with soft tissue three-degree swelling treated from June 2017 to May 2020 was retrospectively analyzed, including 54 males and 22 females, aged from 25 to 50 (38.16±10.24) years. The patients were divided into observation group and control group according to different treatment methods. Twenty-four patients in the observation group were treated by staged surgery stageⅠclosed prying traction reduction and Kirschner wire fixation, stageⅡopen reduction and internal fixation with titanium plate, including 17 males and 7 females, aged from 25 to 50 (36.12±9.56) years. There were 52 patients in the control group, including 37 males and 15 females, aged from 25 to 50 (38.32±10.67) years, these patients were treated with open reduction and internal fixation with titanium plate after the dermatoglyphic signs appeared. The swelling subsidence time, the length of hospitalization days, and the incidence of postoperative incision complications were compared between two groups. The Bhler angle, Gissane angle, and calcaneal varus angle were measured by X-ray before and 6 months after operation. American Orthopedic Foot and Ankle Society (AOFAS) about the ankle hindfoot score was used to evaluate the clinical efficacy. RESULTS: All 76 patients were followed up for 8 to 12 (9.52±2.01) months. The swelling subsidence time and hospitalization days in observation group were (12.12± 3.24) d and (24.53±6.44) d, respectively, which in control group were (15.16±4.16) d and (29.46±9.61) d, with statistical difference between two groups ( CONCLUSION Compared with open reduction and internal fixation with titanium plate after the appearance of dermatoglyphic signs, staged surgery for Sanders type Ⅳ calcaneal fractures with soft tissue three-swelling does not increase the risk of soft tissue complications, and can significantly shorten the patient's swelling subsidence time and hospitalization days, improve the quality of fracture reduction and short term function, and relieve pain.
Ankle Injuries ; Calcaneus/surgery* ; Female ; Foot Injuries ; Fractures, Bone/surgery* ; Humans ; Male ; Retrospective Studies