The arginine methyltransferase Prmt1 coordinates the germline arginine methylome essential for spermatogonial homeostasis and male fertility.

Arginine methylation, catalyzed by the protein arginine methyltransferases (PRMTs), is a common post-translational protein modification (PTM) that is engaged in a plethora of biological events. However, little is known about how the methylarginine-directed signaling functions in germline development. In this study, we discover that Prmt1 is predominantly distributed in the nuclei of spermatogonia but weakly in the spermatocytes throughout mouse spermatogenesis. By exploiting a combination of three Cre-mediated Prmt1 knockout mouse lines, we unravel that Prmt1 is essential for spermatogonial establishment and maintenance, and that Prmt1-catalyzed asymmetric methylarginine coordinates inherent transcriptional homeostasis within spermatogonial cells. In conjunction with high-throughput CUT&Tag profiling and modified mini-bulk Smart-seq2 analyses, we unveil that the Prmt1-deposited H4R3me2a mark is permissively enriched at promoter and exon/intron regions, and sculpts a distinctive transcriptomic landscape as well as the alternative splicing pattern, in the mouse spermatogonia. Collectively, our study provides the genetic and mechanistic evidence that connects the Prmt1-deposited methylarginine signaling to the establishment and maintenance of a high-fidelity transcriptomic identity in orchestrating spermatogonial development in the mammalian germline.

PROCESS Trial: Effect of Duloxetine Premedication for Postherpetic Neuralgia Within 72 Hours of Herpes Zoster Reactivation-A Randomized Controlled Trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN. METHODS: The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis. RESULTS: A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons). CONCLUSIONS: Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.

Vonoprazan and amoxicillin dual therapy for 14 days as the first-line treatment of Helicobacter pylori infection: A non-inferiority, randomized clinical trial.

BACKGROUND: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. METHODS: In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. RESULTS: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). CONCLUSION: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.

The PATCH trial: 5% lidocaine-medicated plaster for trigeminal neuralgia-Results of a multicentric, enriched enrollment, randomized withdrawal, double-blind, vehicle-controlled, parallel-group study.

OBJECTIVE: To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). BACKGROUND: TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. METHODS: The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. RESULTS: The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). CONCLUSIONS: LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.

Copper-catalyzed C2-selective alkynylation of chromones via 1,4-conjugate addition.

Copper-catalyzed selective alkynylation with N-propargyl carboxamides as nucleophiles has been successfully developed for the synthesis of C2-functionalized chromanones. Under optimized reaction conditions, 21 examples were obtained in one-pot procedure through 1,4-conjugate addition. This protocol features readily available feedstocks, easy operations, and moderate to good yields, which provides viable access to pharmacologically active C2-functionalized chromanones.

Synthesis of two-dimensional MoO2 nanoplatelets and its multistep sulfurization into MoS2.

To control the growth of layered two-dimensional structures, such as transition metal dichalcogenide materials or heterostructures, understanding the growth mechanism is crucial. Here, we report the synthesis of ultra-thin MoO2 nanoplatelets through the sublimation of MoO3. Rhombus MoO2 nanoplatelets with the P21/c space group were characterized using various microscopic and spectroscopic techniques. Introducing sulfur sources into the chemical vapor deposition system also leads to the formation of monoclinic MoO2 nanoflakes due to the incomplete sulfurization of MoO3. With a gradual increase in the vapor concentration of sulfur, MoO3 undergoes stepwise reduction into MoS2/MoO2 and eventually into MoS2. Additionally, utilizing MoO2 as a precursor for Mo sources enables the formation of monolayer MoS2 single crystals. This work provides an effective approach for growing MoO2 nanoplatelets and elucidates the mechanism behind the stepwise sulfurization of MoO3.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

[Study on optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum based on statistics of main effective components].

To determine the optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum, the main effective components of cultivated Z. nitidum samples, which originate from various growth years, harvesting months, and different parts were analyzed and compared with the wild samples. HPLC was performed on a Kinetex C18 column(4. 6 mm×100 mm, 2. 6 µm) with the gradient elution of 0. 3% phosphoric acid solution-acetonitrile(80 ∶ 20) containing 0. 2% triethylamine. The flow rate was 1. 0 m L·min-1, and the detection wavelength was 273 nm. The column temperature was 30 ℃. Nitidine chloride and chelerythrine, the main effective components, were determined as the markers. The results showed there was no significant difference in the contents of the main effective components among the roots of wild and cultivated Z. nitidum, as well as the roots and roots + stems of cultivated Z. nitidum. The statistical results of HCA and PCA indicated that the roots and stems could be clearly distinguished, but no distinction could be made between wild and cultivated products, which was consistent with the results of the significance analysis. The total contents of nitidine chloride and chelerythrine in roots and stems of Z. nitidum of 1-6 years old were 0. 114%-0. 256% and 0. 030%-0. 133%, respectively. These results suggested a positive correlation between the content of the main effective components and the growth years. No significant difference was observed between the contents of samples harvested in different seasons, indicating that the harvest season had no effect on the content of the main effective components of the Z. nitidum samples. The total contents of nitidine chloride and chelerythrine of the dried Z. nitidum samples(excluding branches) from three plantation bases were 0. 308%±0. 123% in Yunfu, 0. 192%±0. 025% in Maoming, and 0. 197%±0. 052% in Nanning, respectively, and they were all not less than 0. 15%, or in other words, the roots(including fibrous roots, taproots, and underground stems) and stems(aboveground stems) of Z. nitidum transplanted for more than 2. 5 years can meet the medical requirements. This study demonstrates that the cultivated Z. nitidum could be used as a valid substitute for the wild Z. nitidum, which provides a guarantee for the sustainable development and the application of Z. nitidum resources. The stems and roots could be considered medicinal parts of Z. nitidum. It is recommended to revise the medicinal parts of Z. nitidum to dried roots and stems in the next edition of Chinese Pharmacopoeia, and the medicinal parts can be harvested all year round. In order to ensure the content of effective components and clinical effectiveness, the root and stem should be harvested for medical use after the seedlings of Z. nitidum have been transplanted for more than three years.

[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Effectiveness, Safety, and Predictors of Response to 5% Lidocaine-Medicated Plaster for the Treatment of Patients With Trigeminal Neuralgia: A Retrospective Study.

BACKGROUND: Whether 5% lidocaine-medicated plaster (LMP) is a valuable therapeutic option for the treatment of trigeminal neuralgia (TN) is worth exploring. If LMP is proven effective for TN, positive predictors of the analgesic effects of LMP warrant further investigation. OBJECTIVE: To evaluate the efficacy and safety of LMP for the treatment of TN, and to explore the predictive factors for the treatment efficacy of LMP. METHODS: This is a retrospective and observational study. We analyzed the efficacy of LMP for the treatment of TN between March 2019 and January 2022. The follow-up time was approximately 2 weeks, 1 month, 2 months, and 3 months after LMP treatment. The LMP response was considered the Barrow Neurological Institute (BNI) score of I to III and an improvement in BNI of at least I grade from pretreatment baseline. Univariable and multivariable logistic analyses were performed to identify the predictive factors for LMP response. RESULTS: A total of 103 patients were included and analyzed in this study. LMP was effective in some TN patients, with an efficacy rate of 21.4%, 21.4%, 18.4%, and 16.5% after 2 weeks, 1 month, 2 months, and 3 months of LMP treatment, respectively. The overall adverse event rate associated with LMP was 5.8%, and the reported adverse events were all skin reactions. Facial trigger points (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.07-0.86, P = 0.03) and a lower BNI score (OR = 0.37, 95% CI = 0.07-0.87, P = 0.01) were identified as potential predictors for initial efficacy (2-week follow-up) of LMP treatment. CONCLUSIONS AND RELEVANCE: LMP has been shown to provide effective and sustained analgesia in some TN patients with minimal risk of systemic adverse reactions. Patients with facial trigger points and mild to moderate pain are more likely to benefit from LMP treatment. Our data suggest that LMP may be an effective treatment option for patients with the aforementioned characteristics of TN.

Effect of external electric field on the electronic properties of the AlAs/SiC van der Waals heterostructure.

Type-II van der Waals (vdW) heterostructures are regarded as the optimum candidates for unipolar electronic device applications due to their capacity for spontaneous electron-hole separation. Here, we studied the electronic properties of the AlAs/SiC vdW heterostructure via density functional theory calculations. Results show that the conduction band minimum (CBM) and valence band maximum (VBM) of this heterostructure are mainly contributed by different materials, illustrating that the AlAs/SiC heterostructure has a type-II band alignment. Interestingly, this heterostructure possesses flat valence bands near the Fermi level. In addition, under the modulation of external electric field ranging between -1 V Å-1∼0.8 V Å-1, the band gap of the heterostructure can be tuned continuously, while the band structure maintains a stable type-II band alignment with flat top valence bands. When the electric field exceeds -1 or 0.8 V Å-1, the heterostructure transitions from semiconductor material to metal, indicating the tunability of electronic properties under external fields. These results indicate that the AlAs/SiC heterostructure shows great potential for application in high-performance optoelectronic devices and a strong correlation may exist in this system.

THFS-carbon: a theoretical prediction of metallic carbon allotrope with half-auxeticity, planar tetracoordinate carbon, and potential application as anode for sodium-ion batteries.

Two-dimensional (2D) carbon materials integrated with planar tetracoordinate carbon (ptC) and negative Poisson's ratio (NPR) provide a cornerstone for constructing multifunctional energy-storage devices. As a typical 2D carbon material, the pristine graphene is chemically inert, hindering its application in metal-ion batteries. Introducing the ptC in graphene can break the extended conjugation of π-electrons and lead to an enhanced surface reactivity. Inspired by the unique geometry of [4.6.4.6] fenestrane skeleton with ptC, we theoretically design a ptC-containing 2D carbon allotrope, namely THFS-carbon. It is intrinsically metallic with excellent dynamical, thermal, and mechanical stabilities. The Young's modulus along the x direction (311.37 N m-1) is comparable to that of graphene. Intriguingly, THFS-carbon possesses an in-plane half-NPR distinct from most other 2D crystals. As a promising anode for sodium-ion batteries, THFS-carbon delivers an ultra-high theoretical storage capacity (2233 mA h g-1), a low diffusion energy barrier (0.03-0.05 eV), a low open-circuit voltage (0.14-0.40 V), and a good reversibility for Na insertion/extraction.

Two-dimensional TiCl2: a high-performance anode material for Na-ion batteries with high capacity and fast diffusion.

Na-ion batteries (NIBs) have attracted a great deal of attention for large-scale electric energy storage due to their inherent safety, natural abundant resources, and low cost. The exploration of suitable anode materials is the major challenge in advancing NIB technology. On the basis of first-principles calculations, we systematically explore the potential performance of two-dimensional (2D) TiCl2 as an electrode material for NIBs. Monolayer TiCl2 can be easily exfoliated from the bulk structure with a small exfoliation energy of 0.64 J m-2. It shows good stability, as demonstrated by its high cohesive energy, positive phonon modes, and high thermal stability. Monolayer TiCl2 has high storage capacity (451.3 mA h g-1), low diffusion energy barrier (0.02-0.14 eV), moderate average open-circuit voltage (0.81 V), and small lattice change (2.37%). Moreover, bilayer TiCl2 can significantly enhance the Na adsorption strength but reduce the Na-ion diffusion ability. These results suggest that TiCl2 is a promising anode candidate for NIBs.

RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders.

BACKGROUND: Numerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable. OBJECTIVE: To assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning. METHODS: Forty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT). RESULTS: Eleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up. CONCLUSION: RNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics.

Improved bone and renal safety in younger tenofovir disoproxil fumarate experienced chronic hepatitis B patients after switching to tenofovir alafenamide or entecavir.

INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.

Relationship between severity of obstructive sleep apnea and benign prostatic hyperplasia.

PURPOSE: The cause of benign prostatic hyperplasia (BPH) is controversial, local hypoxia and inflammation being the main two possibilities proposed. The aim of this study was to evaluate the relationship between obstructive sleep apnea (OSA) and BPH. METHODS: The study cohort comprised men from January 2016 to December 2020 in our Sleep Center. These patients were classified into four groups (no, mild, moderate, severe OSA) by apnea-hypopnea indexes (AHI). Logistic regression was used to identify independent risk factors for BPH, after which participants were stratified into younger (age ≤ 40 years) and older groups (age > 40 years) for further analysis. RESULTS: The study cohort comprised 467 patients including 135 younger subjects and 332 older subjects. The prevalence of BPH in the above listed AHI categories was 37.5%, 55.0%, 62.9%, and 52.3%, respectively (p = 0.075). Logistic regression analysis of all patients identified age as a risk factor for BPH (p < 0.001). Stratified analysis according to AHI category found a prevalence of BPH of 0.0%, 13.0%, 33.3%, and 43.9%, respectively, in younger group (p = 0.006), and 52.2%, 71.9%, 71.1%, and 56.3%, respectively, in older group (p = 0.038). Logistic regression analysis found age and AHI were independent risk factors for BPH in younger group (both p < 0.05), whereas only age was identified as a risk factor for BPH in older group (p < 0.001). CONCLUSIONS: Age is an independent risk factor for BPH in men with OSA. AHI is also an independent risk factor for BPH in younger men, suggesting that OSA may affect development of BPH in younger men.

Effectiveness, safety, and predictors of response to ultrasound-guided stellate ganglion blockades for the treatment of patients with chronic migraine: A retrospective and observational study.

BACKGROUND: Whether ultrasound-guided stellate ganglion block (SGB) is a valuable therapeutic option for the treatment of patients with chronic migraine (CM) is worth exploring. If SGB is proven to be effective for CM, the identification of potential predictors for the effectiveness of SGB warrants further investigation. This study aimed to investigate the effectiveness and safety of SGB in patients with CM and to explore the predictive factors for its treatment effectiveness. METHODS: This is a retrospective observational study. We retrospectively analyzed the effects of SGB for the treatment of patients with CM under ultrasound guidance, between January 2018 and June 2022. The follow-up time was approximately 1 month, 2 months, and 3 months after the last SGBs. The response criterion was defined as a reduction in pain intensity of > 50% measured using the most severe numerical rating scale (NRS) score compared to pretreatment baseline, without an increase in the dose or the type of analgesic or anxiolytic/antidepressant medication, otherwise unresponsive to SGB. Univariable and multivariable analyses were performed to identify the predictive factors for SGB response. RESULTS: Ninety-seven patients were included in this study. SGB was effective in most of the CM patients, with an effective rate of 90.7%, 82.5%, and 71.1% after 1, 2, and 3 months of the last SGBs, respectively. At 3-month follow-up, 95.7% responsive patients benefited from repeated SGBs. In patients receiving repeated SGB treatments, the number of SGBs in responsive patients was significantly greater than those in patients with no response at 3-month follow-up (3.41 ± 1.31 vs. 2.68 ± 0.67, p = 0.02). Comorbid anxiety or depression was a negative predictor of SGB effectiveness at 3-month follow-up (B = -0.25, 95% CI -0.45 to -0.05, p = 0.01). The overall adverse events rate associated with ultrasound-guided SGB was 9.3%. There were no serious complications; all adverse events were transient, with hoarseness being the most common adverse event. CONCLUSIONS: Ultrasound-guided SGB was an effective and safe treatment for CM patients. The majority of responsive patients with CM benefited from repeated SGBs. CM patients who needed repeated SGBs may obtain good and sustained analgesic effect after receiving a greater number of SGBs. Patients without comorbidities such as anxiety or depression were more likely to benefit from SGB treatments.

Palladium-Catalyzed Branch- and Z-Selective Allylic C-H Amination with Aromatic Amines.

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.

DNA-PKcs participated in hypoxic pulmonary hypertension.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a common complication of chronic lung disease, which severely affects the survival and prognosis of patients. Several recent reports have shown that DNA damage and repair plays a crucial role in pathogenesis of pulmonary arterial hypertension. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a part of DNA-PK is a molecular sensor for DNA damage that enhances DSB repair. This study aimed to demonstrate the expression and potential mechanism of DNA-PKcs on the pathogenesis of HPH. METHODS: Levels of DNA-PKcs and other proteins in explants of human and rats pulmonary artery from lung tissues and pulmonary artery smooth muscle cells (PASMC) were measured by immunohistochemistry and western blot analysis. The mRNA expression levels of DNA-PKcs and NOR1 in PASMCs were quantified with qRT-PCR. Meanwhile, the interaction among proteins were detected by Co-immunoprecipitation (Co-IP) assays. Cell proliferation and apoptosis was assessed by cell counting kit-8 assay(CCK-8), EdU incorporation and flow cytometry. Rat models of HPH were constructed to verify the role of DNA-PKcs in pulmonary vascular remodeling in vivo. RESULTS: DNA-PKcs protein levels were both significantly up-regulated in explants of pulmonary artery from HPH models and lung tissues of patients with hypoxemia. In human PASMCs, hypoxia up-regulated DNA-PKcs in a time-dependent manner. Downregulation of DNA-PKcs by targeted siRNA or small-molecule inhibitor NU7026 both induced cell proliferation inhibition and cell cycle arrest. DNA-PKcs affected proliferation by regulating NOR1 protein synthesis followed by the expression of cyclin D1. Co-immunoprecipitation of NOR1 with DNA-PKcs was severely increased in hypoxia. Meanwhile, hypoxia promoted G2 + S phase, whereas the down-regulation of DNA-PKcs and NOR1 attenuated the effects of hypoxia. In vivo, inhibition of DNA-PKcs reverses hypoxic pulmonary vascular remodeling and prevented HPH. CONCLUSIONS: Our study indicated the potential mechanism of DNA-PKcs in the development of HPH. It might provide insights into new therapeutic targets for pulmonary vascular remodeling and pulmonary hypertension.