Nf1 in heart development: a potential causative gene for congenital heart disease: a narrative review.

Congenital heart disease is the most frequent congenital disorder, affecting a significant number of live births. Gaining insights into its genetic etiology could lead to a deeper understanding of this condition. Although the Nf1 gene has been identified as a potential causative gene, its role in congenital heart disease has not been thoroughly clarified. We searched and summarized evidence from cohort-based and experimental studies on the issue of Nf1 and heart development in congenital heart diseases from various databases. Available evidence demonstrates a correlation between Nf1 and congenital heart diseases, mainly pulmonary valvar stenosis. The mechanism underlying this correlation may involve dysregulation of epithelial-mesenchymal transition (EMT). The Nf1 gene affects the EMT process via multiple pathways, including directly regulating the expression of EMT-related transcription factors and indirectly regulating the EMT process by regulating the MAPK pathway. This narrative review provides a comprehensive account of the Nf1 involvement in heart development and congenital cardiovascular diseases in terms of epidemiology and potential mechanisms. RAS signaling may contribute to congenital heart disease independently or in cooperation with other signaling pathways. Efficient management of both NF1 and cardiovascular disease patients would benefit from further research into these issues.

[Clinical study of modified Yiyi Baijiang Decoction on psoriasis vulgaris due to dampness-heat accumulation].

The present study observed the clinical effect of modified Yiyi Baijiang Decoction on psoriasis vulgaris and explored its influence on growth factors and inflammatory factors in the serum and skin tissues. A total of 130 patients were randomly divided into control group and experimental group, with 65 cases in each group. The patients in the control group received Acitretin Capsules and Calcipotriol Ointment, and those in the experimental group received modified Yiyi Baijiang Decoction combined with external application for four weeks. The psoriasis area and severity index(PASI), blood vessel count in the superficial dermis(SDBVC), skin thickness(STK), and traditional Chinese medicine(TCM) symptoms were observed before and after treatment. The growth factors [epidermal growth factor(EGF), endothelial cell-specific molecule-1(ESM-1), fibroblast growth factor-23(FGF-23), and transforming growth factor-ß1(TGF-ß1)] and inflammatory factors [nuclear factor-κB(NF-κB), prealbumin(PA), CC chemokine ligand 20(CCL20), and procalcitonin(PCT)] in the serum and skin tissues were detected. The total effective rate was 98.5% in the experimental group, higher than that 83.1% in the control group(P<0.05). Compared with the control group after treatment, the experimental group showed decreased PASI, SDBVC, STK, TCM symptoms, ESM-1, FGF-23, TGF-ß1, NF-κB, CCL20, and PCT(P<0.05), and increased EGF and PA(P<0.05). The incidence of adverse events was 1.5% in the experimental group, lower than that 21.5% in the control group(P<0.05). The results showed that modified Yiyi Baijiang Decoction could effectively relieve skin lesions in patients with psoriasis vulgaris and improve the growth factors and inflammatory factors in the serum and skin lesions, with high safety.

Fiber organic electrochemical transistors based on multi-walled carbon nanotube and polypyrrole composites for noninvasive lactate sensing.

Multi-walled carbon nanotubes (MWCNT) play a synergistic role with conducting polymer in practical applications such as biological sensing. In this paper, multi-walled carbon nanotube and polypyrrole (PPy) composites were prepared on a fiber surface for the first time, and their morphology and electrical properties were characterized. Compared with PPy-coated fiber, the presence of carbon nanotubes induced the growth of large areas of PPy nanowires. In addition, fiber organic electrochemical transistors (FECTs) based on PPy and MWCNT were assembled, showing a higher on/off ratio, better stability, and greater flexibility. The lactate biosensor based on FECTs exhibits high sensitivity, with a correlation coefficient of R = 0.9889, quick response time of 0.6-0.8 s, a wide linear response range of 1 nM-1 mM, and excellent selectivity for lactate. Furthermore, the lactate concentration in human sweat was successfully detected by a FECT-based sensor. The hybrid fibers can be easily woven and placed on fabric simply by stitching. This favorable performance of the FECT-based sensor makes it suitable for noninvasive sensing of lactate. Therefore, it provides a promising platform for future use in healthcare and detection applications. Graphical abstract.

Clinical characteristics and endoscopic treatment of hematospermia with postcoital hematuria.

BACKGROUND: Recurrent hematospermia accompanied by postejaculatory hematuria is a very rare phenomenon, has not been well understood in the clinical setting, and usually leads to misdiagnosis and mistreatment. The aim of this study was to summarize the clinical characteristics, etiologic diagnosis, and endoscopic treatment of hematospermia with postcoital hematuria. METHODS: We collected the clinical data from 39 patients of hematospermia with postcoital hematuria, who were admitted to our hospital from May 2014 to October 2019. The etiologic diagnostic process and endoscopic surgery were analyzed retrospectively, and we observed and evaluated the efficacy and any complications during follow-up. RESULTS: The average age of the 39 patients was 44.1 years (range, 18-61 years), and the disease history ranged from 1 month to 20 years, with a median duration of 24 months. All of the patients were observed by urethrocystoscopy, which showed 38 cases of posterior urethral hemangioma (PUH) or abnormal varicose vessels, and 1 case of anterior urethral hemangioma. Of these, 18 patients underwent transurethral resection of urethral hemangioma, and 21 patients underwent transurethral electrocauterization. Postoperative follow-up ranged from 1 to 56 months, with a median of 16 months. The symptoms disappeared in 37 patients and recurred in 2 patients two to 3 months after the operation. The two recurrent patients were treated again by transurethral electrocauterization, and their symptoms then disappeared. CONCLUSIONS: PUH is the most common cause of hematospermia with postejaculatory hematuria. Herein, we demonstrated that transurethral resection or electrocauterization provides a safe, effective, and minimally invasive method for the treatment of PUH.

Two novel triangular borophenes B3H and B6O: first-principles prediction.

By means of density functional theory calculations, we successfully predict two stable 2D triangular borophenes, namely B3H and B6O. Our results indicate that B3H is a Dirac material and its cone point is located at the K point of the Brillouin zone (BZ). B6O is identified as having a node-line ring and Dirac cones together. Its node-line ring formed by the intersection of the extended energy band from the two Dirac cones located on K point. This modified 2D borophene has great thermal and dynamic stability due to the electron transfer from the triangular boron lattice to the O atoms. The electronic structure of B6O nanofilm demonstrates novel properties such as two Dirac cones, more than 1.3 eV linear dispersion bands at some points of the BZ, as well as excellent transport properties for the extremely high mobility brought by the combination of the node-line semimetal and Dirac cones. Our study may motivate potential applications of 2D materials in nanoelectronics.

[Injection of botulinum-A toxin into bulbospongiosus muscle for primary premature ejaculation: A preliminary clinical study].

OBJECTIVE: To evaluate the efficacy and safety of injection of botulinum-A toxin into the bulbospongiosus muscle in the treatment of primary premature ejaculation (PPE). METHODS: According to the inclusion criteria, we randomly assigned 70 outpatients with PPE to a trial and a control group of equal number, the former injected with 100 U botulinum-A toxin at 10 U/ml and the latter with the same volume of saline into the bulbospongiosus muscle. Then, we obtained the intravaginal ejaculatory latency time (IELT), scores of the Premature Ejaculation Profile (PEP), Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD), and Hospital Anxiety and Depression Scale (HADS), and the incidence of adverse reactions between the two groups before and 4 weeks after treatment. RESULTS: Complete data were obtained from 69 of the patients, 34 in the trial and 35 in the control group. The effectiveness rate was 47.06% (16/34) in the former but 0 in the latter. At 4 weeks after treatment, the patients of the trial group showed a significantly longer IELT than the controls and the baseline (ï¼»2.35 ± 1.83ï¼½ vs ï¼»0.79 ± 0.21ï¼½ and ï¼»0.74 ±+ 0.27ï¼½ min, P < 0.01) and the controls. The patients in the trial group, in comparison with those in the saline control group and the baseline, also exhibited significant improvement in the scores of PEP-ejaculation control (1.21 ± 1.04 vs 0.49 ± 0.56 and 0.47 ± 0.51, P < 0.05), PEP-sexual satisfaction (1.32 ± 1.01 vs 0.71 ± 0.57 and 0.79 ± 0.48, P < 0.05), PEP-PE-related distress (2.12 ± 1.01 vs 2.80 ± 0.68 and 2.76 ± 1.26, P < 0.05), and PEP-PE-induced difficult relationship with the partners (1.38 ± 0.70 vs 2.37 ± 0.55 and 2.12 ± 1.49, P < 0.05). The sexual satisfaction score of the female partners after treatment was markedly improved in the trial group as compared with the control group and the baseline (1.18 ± 1.00 vs 0.57 ± 0.50 and 0.62 ± 0.60, P < 0.05). There were no statistically significant differences in MSHQ-EjD and HADS scores between the two groups before and after treatment. Adverse reactions were observed in 6 cases (17.65%) in the trial group, including 4 cases of decreased erectile hardness (11.76%) and 2 cases of incomplete urination (5.88%), which occurred from the 3 to 4 days after injection, and those with decreased erectile hardness could complete sexual intercourse without any other treatment and recovered after 3 weeks. CONCLUSIONS: Injection of botulinum-A toxin into the bulbospongiosus muscle can be used as an option for the treatment of PPE. Its clinical application value, however, needs to be verified by further studies with larger samples.

Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin.

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors.

[Effects of Xialiqi Capsules on the expressions of PCNA and caspase-3 in rats withbenign prostatic hyperplasia].

OBJECTIVE: To explore the effects of Xialiqi Capsules(XLQ) on the expressions of the proliferating cell nuclear antigen (PCNA) and caspase-3 in the prostate tissue of the BPH rat model. METHODS: Fifty male SD ratswereequally randomized into groups A (sham operation control), B (BPH model control), C (high-dose XLQ), D (low-dose XLQ), and E (finasteridecontrol) andthe BPH modelswere established by subcutaneous injection of testosterone propionate at 0.5 mg per kilogram of the body weight per day for 30 days after castration. After modeling, the animals in groups A and B were treated intragastricallywith normal saline, while those in C, D, and E with XLQ at 1.20 and 0.61 g per kilogram of the body weight per day or finasterideat 0.8 mg per kilogram of the body weight per day, respectively, all for 30 days. Then,the bilateral prostates were harvestedfrom the rats for calculation of the prostatic index (prostate wet weight/ body weight) and determination of the expressions of PCNA and caspase-3 in the prostate tissue by immunohistochemistry and immunofluorescence staining, respectively. RESULTS: The prostate wet weight and prostate index were significantly increased in group B as compared with group A, (ï¼»1326±60ï¼½ vsï¼»471±17ï¼½ g, P<0.01; ï¼»2.89±0.18ï¼½ vs ï¼»1.06±0.06ï¼½ mg/g, P<0.01), but decreased in groups C (ï¼»914±36ï¼½ g;ï¼»2.02±0.08ï¼½ mg/g), D (ï¼»1 099±46ï¼½g;ï¼»2.39±0.11ï¼½ mg/g), and E (ï¼»817±53ï¼½ g;ï¼»1.83±0.10ï¼½ mg/g)in comparison with B (P<0.01), with statistically significant differences among groups C, D, and E(P<0.01) and most significantly in E.The PCNA level in the prostate tissue wasremarkably higher in group B than in A, but lower in groups C, D and E than in B. The expression of caspase-3 was down-regulatedin group B as compared with A, but up-regulated in groups C, D and E in comparison with B, most significantly in E. CONCLUSIONS: Xialiqi Capsules can effectively reduce the prostate wet weight and prostatic index of in rats with BPH by inhibiting the level of PCNA and promoting the expression of caspase-3.

Ion sensors based on novel fiber organic electrochemical transistors for lead ion detection.

Fiber organic electrochemical transistors (FECTs) based on polypyrrole and nanofibers have been prepared for the first time. FECTs exhibited excellent electrical performances, on/off ratios up to 10(4) and low applied voltages below 2 V. The ion sensitivity behavior of the fiber organic electrochemical transistors was investigated. It exhibited that the transfer curve of FECTs shifted to lower gate voltage with increasing cations concentration, the sensitivity reached to 446 µA/dec in the 10(-5)-10(-2) M Pb(2+) concentration range. The ion selective properties of the FECTs have also been systematically studied for the detection of potassium, calcium, aluminum, and lead ions. The devices with different cations showed great difference in response curves. It was suitable for selectively monitoring Pb(2+) with respect to other cations. The results indicated FECTs were very effective for electrochemical sensing of lead ion, which opened a promising perspective for wearable electronics in healthcare and biological application. Graphical Abstract The schematic diagram of fiber organic electrochemical transistors based on polypyrrole and nanofibers for ion sensing.

[Lipopolysaccharide affects testicular histology and reproductive endocrine function in male rats].

OBJECTIVE: To study the influence of lipopolysaccharide (LPS)-induced inflammation on the testicular histology and reproductive endocrine function in male rats and investigate the possible mechanism of inflammation affecting male fertility. METHODS: Thirty-six male SD rats were randomly divided into a control group (A) and three LPS intervention groups (B, C, and D) to receive saline and LPS (5 mg/kg i. p, once), respectively. The animals in groups B, C, and D were killed by anesthesia at 12, 24, and 72 hours after treatment. Histopathological changes in the left testis of the rats were observed by HE staining and the levels of the reproductive hormones T, FSH, and LH in the serum were determined by ELISA. RESULTS: Compared with group B, group A showed clear structure of seminiferous tubules, orderly arrangement of spermatogenic cells, a slightly decreased number of sperm in some seminiferous tubular lumens, and shed spermatogenic cells in the rat testis tissue; group C exhibited thinner seminiferous epithelia, disordered structure of seminiferous tubules, irregular arrangement of spermatogenic cells, decreased number of mature sperm and obvious shedding of spermatogenic cells in seminiferous tubular lumens; group D manifested similar findings to those of group C, with even more shed spermatogenic cells that blocked the tubular lumens. The levels of serum T, LH, and FSH were (0.490 +/- 0.028) ng/ml, (6.290 +/- 0.515) ng/L, and (1.837 +/- 0.127) IU/L in group A, (0.460 +/- 0.024) ng/ml, (5.881 +/- 0.124) ng/L, and (1.707 +/- 0.098) IU/L in group B, (0.417 +/- 0.021) ng/ml, (5.123 +/- 0.271) ng/L, and (1.620 +/- 0.115) IU/L in group C, and (0.378 +/- 0.021) ng/ml, (4.504 +/- 0.279) ng/L and (1.562 +/- 0.216) IU/L in group D, all decreased in group B as compared with A (P > 0.05). The decreases of T and LH were extremely significant (P < 0.01) and that of FSH was significant in groups C and D (P < 0.05) in comparison with A. CONCLUSION: LPS-induced inflammation affects the testicular tissue and reproductive endocrine function of male rats, resulting in decreased levels of serum T, LH, and FSH.

[Reproductive hormone levels and relevant parameters in middle-aged and older men in the urban area of Nanjing].

OBJECTIVE: To investigate the status of male reproductive health among middle-aged and older men in the urban area of Nanjing. METHODS: We collected the laboratory results of 884 middle-aged and older men aged 55 - 89 years from the Xuanwu District of Nanjing present for routine physical examinations, including those of blood routine tests, liver and kidney function, blood glucose, blood lipid, and total prostate specific antigen (TPSA), as well as such reproductive hormone indexes as total serum testosterone (TT), free serum testosterone (fT), and sex hormone binding globulin (SHBG). We also obtained the above reproductive hormone indexes from 119 young and middle-aged men aged 20 - 39 years as controls. RESULTS: Aging-related changes were found in the 50 percentiles of all the reproductive hormones and relevant parameters but those of TT and E2, with gradual increases in LH, FSH and SHBG and decreases in fT, TSI and fTI. Comparison of reproductive hormones and relevant parameters by Mann-Whitney U test did not show any statistically significant differences in the TT level between any two of the five age groups (20 - 39, 55 - 59, 60 - 69, 70 - 79, and > or = 80 yr) (P > 0.05) except between the control and > or = 80 yr groups and the 60 - 69 and > or = 80 yr groups (P < 0.05), nor in the E2 level between any two groups, nor in the levels of LH and FSH except between the 55 - 59 and 60 - 69 yr groups and the 70 - 79 and > or = 80 yr groups, and nor in the levels of fT and TSI except between the 55 - 59 and 60 - 69 yr groups. However, there were significant differences in the levels of SHBG and fTI between any two age groups. Spearman correlation analysis revealed that fT, TSI, and fTI were correlated negatively with aging and LH (P < 0.05, I r I > 0.5) but weakly positively with cholesterol, blood glucose and hemoglobin (P < 0.05, /r/ < 0.5), SHBG and LH positively with aging, SHBG weakly negatively with blood glucose and hemoglobin, LH weakly negatively with hemoglobin, and TT weakly negatively with aging but positively with hemoglobin. CONCLUSION: The levels of serum testosterone, particularly that of fT, declined with aging in middle-aged and older men in the urban area of Nanjing, which may contribute to abnormal lipid metabolism, low hemoglobin and high blood glucose.

Comparison of SOX and CAPOX in patients with advanced gastric cancer after laparoscopic D2 gastrectomy: A randomized controlled trial.

BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.

[Testosterone deficiency: an independent risk factor of cardiovascular disease].

Serum testosterone levels and gonad function decline with the aging of males. Large-scale epidemiological investigations, mechanism researches and clinical studies conducted in recent years have shown that physiological androgens are critical for the protection of the cardiovascular system. Testosterone deficiency in aging males is associated with several cardiovascular risk factors which include hyperlipidemia, diabetes, hypertension, thrombogenic and fibrinolytic dysfunction and inflammation. It can also lead to endothelial and vascular dysfunction, accelerate the formation of atherosclerosis and increase the morbidity of cardio-vascular disease.

[Lipopolysaccharide affects male reproductive function through Toll-like receptors].

Reproductive tract infection is one of the factors of male infertility, but the mechanisms responsible are hitherto poorly defined. Recent studies show that one of the microbial pattern-recognition receptors, Toll-like receptor (TLR) signaling pathway, plays a critical role in inflammation-induced male infertility. Lipopolysaccharide (LPS), a major component in the cell wall of gram-negative bacteria, could induce inflammatory response through TLRs. A large number of researches suggest that TLRs express widely in the male reproductive tract and LPS-induced inflammatory reaction through TLRs may affect male fertility. This article presents an overview on how LPS-induced inflammation through TLRs affects male fertility in terms of its influence on the testis, epididymis and sperm quality.

Highly Conductive, Ultrastrong, and Flexible Wet-Spun PEDOT:PSS/Ionic Liquid Fibers for Wearable Electronics.

Conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) fibers with high electrical conductivity, flexibility, and robustness are urgently needed for constructing wearable fiber-based electronics. In this study, the highly conductive (4288 S/cm), ultrastrong (a high tensile strength of 956 MPa), and flexible (a low Young's modulus of 3.8 GPa) PEDOT:PSS/1-ethyl-3-methylimidazolium dicyanamide (EMIM:DCA) (P/ED) fiber was prepared by wet-spinning and a subsequent H2SO4-immersion-drawing process. As far as we know, this is the best performance of the PEDOT:PSS fiber reported so far. The structure and conformation of the P/ED fiber were characterized by FESEM, XPS, Raman spectroscopy, UV-vis-NIR spectroscopy, and WAXS. The results show that the high performances of the P/ED fiber are mainly attributed to the massive removal of PSS and high degree of crystallinity (87.9%) and orientation (0.71) of PEDOT caused by the synergistic effect of the ionic liquid, concentrated sulfuric acid, and high stretching. Besides, the P/ED fiber shows a small bending radius of 0.1 mm, and the conductivity of the P/ED fiber is nearly unchanged after 1000 repeated cycles of bending and humidity changes within 50-90%. Based on this, various P/ED fiber-based devices including the circuit connection wire, thermoelectric power generator, and temperature sensor were constructed, demonstrating its wide applications for constructing flexible and wearable electronics.

[Correlation between macrophage chemotaxis and disease severity in patients with knee osteoarthritis].

OBJECTIVE: To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity. METHODS: Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out. RESULTS: The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01). CONCLUSION: The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.

Power of the Sine Hamiltonian Operator for Estimating the Eigenstate Energies on Quantum Computers.

Quantum computers have been shown to have tremendous potential in solving difficult problems in quantum chemistry. In this paper, we propose a new classical-quantum hybrid method, named as power of sine Hamiltonian operator (PSHO), to evaluate the eigenvalues of a given Hamiltonian (H). In PSHO, for any reference state |φ0⟩, the normalized energy of the sinn(H^τ)|φ0⟩ state can be determined. With the increase of the power, the initial reference state can converge to the eigenstate with the largest |sin(Eiτ)| value in the coefficients of the expansion of |φ0⟩, and the normalized energy of the sinn(H^τ)|φ0⟩ state converges to Ei. The ground- and excited-state energies of a Hamiltonian can be determined by taking different τ values. The performance of the PSHO method is demonstrated by numerical calculations of the H4 and LiH molecules. Compared with the current popular variational quantum eigensolver method, PSHO does not need to design the ansatz circuits and avoids the complex nonlinear optimization problems. PSHO has great application potential in near-term quantum devices.

Orthogonal State Reduction Variational Eigensolver for the Excited-State Calculations on Quantum Computers.

Variational quantum eigensolver (VQE) is a promising method for ground-state calculations on current noisy intermediate-scale quantum computers. However, the research progress of excited-state calculations on quantum computers is relatively slow. In order to extend the framework of VQE for excited-state calculations, we propose a new algorithm, orthogonal state reduction variational eigensolver (OSRVE), to determine the energies of excited states. Theoretical derivations prove that the optimized state in the OSRVE method can ensure the energy minimum and orthogonality constraint simultaneously, and OSRVE is also applicable for the degenerate state. The performance of OSRVE is demonstrated by numerical calculations of the H4 and H2O molecules. Compared with other excited-state calculation algorithms, OSRVE has obvious advantages in calculating lower-order excited states. This work extends the VQE algorithm to excited-state calculations, and OSRVE can be implemented on near-term quantum computers.

Somatostatin Treatment for Ectopic ACTH Syndrome due to Pancreatic Neuroendocrine Tumors: Review of the Literature.

Objectives: To analyze and summarize the effect of SSA treatment on EAS due to p-NETs (EAS-p-NETs). Methods: Thirteen patients with EAS-p-NETs treated with SSAs at our center or described in the literature were included in this study. Clinical characteristics, laboratory data, imaging studies, histopathologic results, the effect of SSA treatment, and the prognosis of these EAS-p-NET patients were evaluated. Results: Four males and 9 females with an average age of 42.9 years were included in the study. The mean duration of follow-up was 38.8 ± 28.2 months. As one of the combined treatment measures, SSAs controlled the levels of ACTH and cortisol in 9 of the 13 patients (69.2%). Partial response was observed in 3 patients (23.1%), stable disease in 2 patients (15.4%), and progressive disease in 6 patients (46.2%). The median time to tumor progression was 24 months, and the median overall survival was 61 months. The side effects of SSA treatment included temporary mild abdominal pain, diarrhea, gallstones, and cholecystitis. Conclusions: As a supplemental therapy, SSA treatment led to clinical and biochemical improvement with a good safety profile in patients exhibiting EAS-p-NET with metastasis. However, tumor progression was inhibited by SSA treatment in only a few patients. Combined with other treatments, SSAs may improve the prognosis of patients with EAS-p-NETs.

Human coronaviruses and therapeutic drug discovery.

BACKGROUND: Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MAIN TEXT: A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. CONCLUSIONS: During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.