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Trial Design: Our study is to investigate the feasibility and effectiveness of multiple cardiovascular factors intervention (MFI) in type 2 diabetes patients in China's primary care setting., Methods: We performed a cluster randomized trial to compare the proportion of patients achieved the targets between usual care group (control, 9 sites, n = 868) and MFI group (8 sites, n = 739) among patients with type 2 diabetes in primary care setting. Logistic regression model with random effects was used to estimate the association of the effect of intervention and the proportion achieved the targets., Results: At baseline, the end of 1 year, and 2 years follow-up, the proportion of patients achieved all 3 target goals (HbA1c < 7.0%, blood pressure < 130/80 mm Hg and low-density lipoprotein cholesterol < 2.6 mmol/L) were 5.7%, 5.9%, 5.7% in the control group and 5.9%, 10.6%, 12.3% in the MFI group. After adjusting sex, age, diabetes duration, body mass index, HbA1c, blood pressure, and low-density lipoprotein cholesterol at baseline, there was no difference between the 2 groups (OR (95% CI): 1.27 (0.38-4.27) and 1.86 (0.79-4.38) for the first year and second year, respectively). When stratified by payment method, the patients with medical insurance or public expenses had a higher proportion achieved target goals (6.9% vs 16.4%, OR (95% CI): 2.30 (1.04-5.08)) in the second year., Conclusions: The controlling of cardiovascular risk factor targets remains suboptimal among patients with type 2 diabetes in primary care setting. MFI in type 2 diabetes improved cardiovascular disease risk profile, especially in the patients with medical insurance., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

We demonstrate an on-chip Y b 3+ -doped lithium niobate (LN) microdisk laser. The intrinsic quality factors of the fabricated Y b 3+ -doped LN microdisk resonator are measured up to 3.79×10 5 at a 976 nm wavelength and 1.1×10 6 at a 1514 nm wavelength. The multi-mode laser emissions are obtained in a band from 1020 to 1070 nm pumped by a 984 nm laser and with the low threshold of 103µ W , resulting in a slope efficiency of 0.53% at room temperature. Furthermore, both the second-harmonic frequency of pump light and the sum frequency of the pump light and laser emissions are generated in the on-chip Y b 3+ -doped LN microdisk, benefiting from the strong χ (2) nonlinearity of LN. These microdisk lasers are expected to contribute to the high-density integration of a lithium niobate on insulator-based photonic chip.

We demonstrate a C-band wavelength-tunable microlaser with an E r 3+ -doped high quality (∼1.8×10 6 ) lithium niobate microdisk resonator. With a 976 nm continuous-wave pump laser, lasing action can be observed at a pump power threshold lower than 400 µW at room temperature. Furthermore, the microdisk laser wavelength can be tuned by varying the pump laser power, showing a tuning efficiency of ∼-17.03 p m / m W at low pump power below 13 mW, and 10.58 pm/mW at high pump power above 13 mW.

Isolated follicle stimulating hormone (FSH) deficiency due to mutations in FSHβ is an extremely rare autosomal recessive disease that has only been reported in ten patients to date. Symptoms of the disease include amenorrhoea and hypogonadism in women and azoospermia and normal testosterone levels in men. This study describes a Chinese male patient who presented with cryptorchidism and infertility. His serum hormonal profile revealed low FSH, elevated LH and normal testosterone levels. Sequence analysis identified a novel homozygous mutation in the FSHβ gene (c.343C > T) predicted to result in a premature termination codon and a truncated FSH protein (p.R115X). Both parents were heterozygous carriers of the mutation with normal pubertal development and fertility. The patient's testicular volume increased after one year of exogenous FSH replacement therapy at which point spermatocytes were detected in seminal samples, indicating potential future spermatogenesis. The expanded spectrum of FSHβ mutations and associated clinical manifestations described in this study may improve the diagnosis and treatment of this disease., (Copyright © 2017. Published by Elsevier Masson SAS.)

Objective: To investigate the therapeutic effect of pulsatile GnRH (gonadorelin) pump on female patients with idiopathic hypogonadotropic hypogonadism (IHH)., Methods: In this retrospective study, five female IHH patients were recruited. Patients were treated with pulsatile gonadorelin (10 µg per 90 min) via a pump for at least 12 weeks. Serum gonadotropins and sex steroid levels were measured, and menses were recorded., Results: After one-week treatment, luteinizing hormone (LH) level increased from (2.2 ± 2.0) U/L to (5.4 ± 2.5) U/L (P=0.028), follicle-stimulating hormone(FSH) level increased from (3.7 ± 2.7) U/L to(6.3 ± 1.0) U/L (P=0.162), and estradiol (E2) level increased from (58 ± 13) pmol/L to (260 ± 97) pmol/L (P=0.011). Menstrual bleeding was observed in 4 patients after starting treatment for 35-55 days and two natural pregnancies were reported. No menstrual bleeding was reported in another patient. The frequency of pulsatile GnRH had to be adjusted according to endogenous GnRH secretion during the follicular phase of normal women and regular menses were induced., Conclusions: Pulsatile GnRH is effective in treating female IHH. A constant frequency of pulsatile GnRH is suitable for most of IHH patients. However, for those who failed to produce regular menses, adjusting pulsatile frequency to imitate the physiological rhythm of GnRH may be an alternative option.

Objective: To explore the relationships between pathogenic gene mutations and extra-gonadal manifestations in male patients with congenital hypogonadotropic hypogonadism (CHH)., Methods: A total of 15 genes were screened in 259 CHH patients by massively parallel DNA sequencing. The identified pathogenic mutations were confirmed by Sanger polymerase chain reaction (PCR). The extra-gonadal features in all patients were recorded., Results: Gene mutations were detected in 83 (32.0%) patients, which included FGFR1 (n=20), PROKR2 (n=19), CHD7 (n=16), KAL1 (n=14) and other genes (n=14), such as PROK2, FGF8, GNRHR, KISS1R, NELF and WDR11. Patients with KAL1 mutation displayed CHH related family history (n=5) and obesity (n=3). Patients with FGFR1 mutation presented with short stature (n=3), testicular hydrocele (n=2), lip-palate cleft (n=2) and dental dysplasia (n=1). Patients without detectable mutations may also exhibit obesity, mental retardation and short stature., Conclusions: CHH patients may present with extra-gonadal manifestations, including anosmia, obesity, dental dysplasia, short stature and mental retardation. An obscure relationships could be found between the clinical features and different gene mutations, but it is difficult to speculate the types of pathogenic gene mutations according to these extra-gonadal manifestations.

Objective: To compare the efficacies of pulsatile gonadotropin-releasing hormone (GnRH) versus human chorionic gonadotropin/human menopausal gonadotropin (HCG/HMG) for spermatogenesis in male idiopathic hypogonadotropic hypogonadism (IHH)., Methods: For this retrospective study, a total of 92 male IHH outpatients from May 2010 to October 2014 were recruited and categorized into GnRH (n = 40) and HCG/HMG (n = 52) groups. Each subject selected one specific therapy voluntarily. The gonadotropin levels were measured in the first week and monthly post-treatment in GnRH group. And serum total testosterone (TT), testicular volume (TV) and rate of spermatogenesis were observed monthly post-treatment in two groups. Spermatogenesis, TT and TV were compared between two groups., Results: All IHH patients were treated for over 3 months. The median follow-up periods in GnRH and HCG/HMG groups was 8.2 (3.0-18.4) and 9.2 (3.0-18.6) months respectively (P = 0.413). In GnRH group, LH ((0.5 ± 0.6) vs (3.4 ± 2.4) U/L, P < 0.01) and FSH ((1.3 ± 1.1) vs (5.8 ± 3.8) U/L, P < 0.01) increased after 1-week treatment. In GnRH group, at the end of follow-up, TT ((1.0 ± 1.0) vs (7.4 ± 5.2) nmol/L, P < 0.01) and TV ((2.3 ± 1.5) vs (8.1 ± 4.0) ml, P < 0.01) significantly increased compared to baseline. In HCG/HMG group, TT ((0.8 ± 0.6) vs (14.4 ± 8.0) nmol/L, P < 0.01) and TV ((2.3 ± 2.1) vs (7.6 ± 4.2) ml, P < 0.01) significantly increased after therapy. The success rate of spermatogenesis was 50.0% (20/40) in GnRH group versus 28.8% (15/52) in HCG/HMG group (P = 0.038). GnRH group required a shorter treatment time for initial sperm appearance than HCG/HMG group ((6.5 ± 3.1) vs (10.8 ± 3.7) months, P = 0.001)., Conclusion: Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

Objective: To evaluate the effect of pretreatment with erythropoietin (EPO) on disordered pro- and anti- inflammatory balance in rats with severe acute pancreatitis (SAP) and explore the underlying mechanisms., Methods: Ninety healthy male SD rats were randomized equally into sham-operated group, SAP group and EPO pretreatment group. SAP model was induced in the latter two groups by retrograde injection of 1 ml/kg 3.5% sodium traurocholate into the biliopancreatic duct. In EPO group, 3000 U/kg EPO (1000 U/ml) was administered intravenously 1 h before SAP, and normal saline was administered in the other two groups. Serum amylase activity, interleukin-10 (IL-10)and IL-18 levels were measured at different time points after the operation. The translocation and activation of nuclear factor-κB (NF-κB) in the pancreatic tissue was detected using immunofluorescence staining, and pancreatic pathologies were evaluated., Results: Compared with SAP group, EPO group showed a markedly decreased activation rate of NF-κB after SAP except for 12 h (P<0.05), significantly decreased serum amylase activity at 3, 6, and 12 h (P<0.05) and decreased serum IL-18 levels at 3, 6, 24 h (P<0.05), whereas serum IL-10 underwent no significant changes. The rats in EPO group showed an obviously milder pancreatic pathology than those in SAP group at 6, 12, and 24 h (P<0.05)., Conclusion: EPO can effectively inhibit NF-κB activation by regulating the inflammatory mediators and restoring the pro-and anti-inflammatory balance to alleviate SAP in rats.