Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

Silicon and selenium alleviate cadmium toxicity in Artemisia selengensis Turcz by regulating the plant-rhizosphere.

Soil cadmium (Cd) pollution has emerged as a pressing concern due to its deleterious impacts on both plant physiology and human well-being. Silicon (Si) is renowned for its ability to mitigate excessive Cd accumulation within plant cells and reduce the mobility of Cd in soil, whereas Selenium (Se) augments plant antioxidant capabilities and promotes rhizosphere microbial activity. However, research focusing on the simultaneous utilization of Si and Se to ameliorate plant Cd toxicity through multiple mechanisms within the plant-rhizosphere remains comparatively limited. This study combined hydroponic and pot experiments to investigate the effects of the combined application of Si and Se on Cd absorption and accumulation, as well as the growth and rhizosphere of A. selengensis Turcz under Cd stress. The results revealed that a strong synergistic effect was observed between both Si and Se. The combination of Si and Se significantly increased the activity and content of enzymes and non-enzyme antioxidants within A. selengensis Turcz, reduced Cd accumulation and inhibiting its translocation from roots to shoots. Moreover, Si and Se application improved the levels of reducing sugar, soluble protein, and vitamin C, while reducing nitrite content and Cd bioavailability. Furthermore, the experimental results showed that the combination of Si and Se not only increased the abundance of core rhizosphere microorganisms, but also stimulated the activity of soil enzymes, which effectively limited the migration of Cd in the soil. These findings provided valuable insights into the effective mitigation of soil Cd toxicity to plants and also the potential applications in improving plant quality and safety.

Adding Letrozole to Growth Hormone and Gonadotropin-Releasing Hormone Analog Increases Height in Girls With Short Stature: A Hospital Record-Based Retrospective Study.

OBJECTIVE: There have been rare data on letrozole for height improvement in girls. This study aimed to clarify the efficacy and safety of combination therapy with recombinant human growth hormone (rhGH), GnRHa, and letrozole in improving the height of girls with short stature and advanced bone age. METHODS: This was a hospital record-based retrospective study. Follow-up was conducted on girls with short stature who received treatment with rhGH, GnRHa, and letrozole in our hospital. The treatment group included a total of 29 participants. Before treatment, the mean age of the patients was 11.17 years, and the mean treatment duration was 17.31 months. The control group consisted of 29 short-statured girls who received rhGH/GnRHa treatment, with the mean age and treatment duration of 12.43 years and 16.59 months, respectively. RESULTS: The predicted adult heights (PAHs) before and after treatment were 155.38 and 161.32 cm (P < .001). The ΔPAH in the treatment group was 4 cm higher than that in the control group (5.85 vs 1.82 cm, P < .001). Significant differences were noted in the height standard deviation scores of bone age (P < .001) and chronological age (P = .003) before and after treatment. There was an increasing body mass index during therapy (P = .039). The height gain was 8.71 ± 4.46 cm, and the growth rate was 6.78 ± 3.84 cm per year. CONCLUSION: Combined treatment with GH, GnRHa, and letrozole can enhance the adult height and PAH in short-statured girls, and no significant side effects have been reported.

From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective.

Background: Acute kidney injury (AKI) is a severe condition marked by rapid renal function deterioration and elevated mortality, with traditional biomarkers lacking sensitivity and specificity. Rare tubulointerstitial diseases encompass a spectrum of disorders, primarily including monogenic diseases, immune-related conditions, and drug-induced tubulointerstitial diseases. The clinical manifestations vary from electrolyte and acid-base imbalances to kidney function insufficiency, which is associated with AKI in up to 20% of cases. Evidence indicated that rare tubulointerstitial diseases might provide new conceptual insights and perspectives for novel biomarkers and potential therapeutic strategies for AKI. Summary: Autosomal dominant tubulointerstitial kidney disease (ADTKD) and Fanconi syndrome (FS) are rare tubulointerstitial diseases. In ADTKD, UMOD and REN are closely related to AKI by affecting oxidative stress and tubuloglomerular feedback, which provide potential new biomarkers for AKI. Both rare tubulointerstitial diseases and AKI share etiologies and treatment responses. From the mechanism standpoint, rare tubulointerstitial diseases and AKI involve tubular transporter injury, initially manifesting as tubular dysfunction in tubulointerstitial disorder and progressing to AKI because of the programmed cell death with apoptosis, pyroptosis, or necroptosis of proximal tubule cells. Additionally, mitochondrial dysfunction has been identified as a common mechanism in both tubulointerstitial diseases and AKI induced by drugs, pSS, or monoclonal diseases. In the end, both AKI and FS patients and animal models responded well to the therapy of the primary diseases. Key Messages: In this review, we describe an overview of ADTKD and FS to identify their associations with AKI. Mitochondrial dysfunction contributes to rare tubulointerstitial diseases and AKI, which might provide a potential therapeutic target.

Selenium and Bacillus proteolyticus SES increased Cu-Cd-Cr uptake by ryegrass: highlighting the significance of key taxa and soil enzyme activity.

Many studies have focused their attention on strategies to improve soil phytoremediation efficiency. In this study, a pot experiment was carried out to investigate whether Se and Bacillus proteolyticus SES promote Cu-Cd-Cr uptake by ryegrass. To explore the effect mechanism of Se and Bacillus proteolyticus SES, rhizosphere soil physiochemical properties and rhizosphere soil bacterial properties were determined further. The findings showed that Se and Bacillus proteolyticus SES reduced 23.04% Cu, 36.85% Cd, and 9.85% Cr from the rhizosphere soil of ryegrass. Further analysis revealed that soil pH, organic matter, soil enzyme activities, and soil microbial properties were changed with Se and Bacillus proteolyticus SES application. Notably, rhizosphere key taxa (Bacteroidetes, Actinobacteria, Firmicutes, Patescibacteria, Verrucomicrobia, Chloroflexi, etc.) were significantly enriched in rhizosphere soil of ryegrass, and those taxa abundance were positively correlated with soil heavy metal contents (P < 0.01). Our study also demonstrated that in terms of explaining variations of soil Cu-Cd-Cr content under Se and Bacillus proteolyticus SES treatment, soil enzyme activities (catalase and acid phosphatase) and soil microbe properties showed 42.5% and 12.2% contributions value, respectively. Overall, our study provided solid evidence again that Se and Bacillus proteolyticus SES facilitated phytoextraction of soil Cu-Cd-Cr, and elucidated the effect of soil key microorganism and chemical factor.

Efficacy of photodynamic therapy as an adjunct to scaling and root planing on clinical parameters and microbial composition in subgingival plaque of periodontitis patients: A split-mouth randomized clinical trial.

BACKGROUND: The aim of this study was to assess the efficacy of photodynamic therapy (PDT) as an adjunct to scaling and root planing (SRP) on clinical parameters and microbial composition in subgingival plaque of periodontitis patients. METHODS: Seventeen patients were included in this split-mouth randomized clinical trial. Sites with probing pocket depth (PPD) ≥5 mm in combination with bleeding on probing in different quadrants were randomized into the control group, the group with a single PDT application right after SRP, and the group with three repeated PDT applications 1 week after SRP. The subgingival plaque was collected for 16S rRNA gene sequencing at baseline, Week 2, and Week 8. RESULTS: Seventeen patients with 60 sites completed this 8-week follow-up, and 157 subgingival plaques were successfully analyzed by sequencing. Significant improvements were observed in two primary outcomes: PPD at Week 8 and subgingival microbial composition. Compared to the control group, the repeated-PDT group showed a notable improvement in PPD, substantial alterations in the microbial profile, including a reduction in α-diversity and anaerobic bacteria, and an increase in aerobic bacteria at Week 2. Secondary outcomes, such as clinical attachment level and sulcus bleeding index, also showed improvement at Week 8. Furthermore, both the single- and repeated-PDT groups exhibited a decrease in periodontopathogens and an increase in beneficial bacteria compared with baseline. CONCLUSION: PDT promotes changes in the microbial composition of periodontitis patients' subgingival plaque in a direction favorable to periodontal health, and repeated PDT is a promising adjunctive therapy for periodontal treatment.

Analysis of ten-year teaching evaluation of oral microbiology lab curriculum.

BACKGROUND: Based on the updated teaching philosophy of oral microbiology, Wuhan University School of Stomatology initiated a reform in the teaching of oral microbiology in 2009. As part of this reform, an oral microbiology laboratory course was introduced to cultivate students' fundamental skills, professional competence, comprehensive abilities, and innovation capabilities through experimental design. This paper provides thorough examination of the teaching experiment findings from 2013 to 2022, a ten-year timeframe, building on earlier data. METHODS: The curriculum targets fourth-year undergraduate students in a five-year program and adopts a cooperative learning approach. The experimental teaching mainly involves four parts: plaque collection and processing, isolation and cultivation of dental plaque bacteria, staining and biochemical identification of dental plaque bacteria. This article presents a comprehensive analysis of the student experiment results from 2013 to 2022. Statistical analysis was conducted using the chi-square test to assess whether there were any differences in students' experimental grades between different years. A significance level of P < 0.05 was considered statistically significant. Additionally, we evaluated the impact of teaching methods and educational systems on improving students' practical skills and overall innovative abilities. RESULTS: The performance of 664 undergraduate students showed improvement in the oral microbiology laboratory course, with a noticeable decrease in the proportion of "C" grades in Experiments 2, 3, and 4 compared to Experiment 1. These results indicate that the laboratory course enhanced students' academic achievements, aiding their understanding and mastery of course content, and received positive feedback from the students. CONCLUSION: This lab curriculum, through systematic laboratory teaching and practical experience, contributes to the enhancement of students' professional skills and research abilities. It fosters students' interest in scientific research and improves the quality of dental education.

Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.

Genetic and clinical characterization of familial renal glucosuria.

Background: Familial renal glucosuria (FRG) is a hereditary disorder caused by variants in SLC5A2 encoding sodium-glucose cotransporter 2 (SGLT2). In this study, we aimed to characterize proximal tubule solute transport, glucagon secretion and the genotype-phenotype relationship in FRG patients. Methods: We sequenced SLC5A2 and PDZK1IP1 in 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients. We built an open-source online calculator of RTG, evaluated the proximal tubule transport of amino acid, uric acid and phosphate, and explored glucagon secretion after glucose ingestion in FRG patients. Results: We identified 12 novel SLC5A2 variants (G484D, R564W, A212S, c.574+1G>C, W649*, S592Cfs*6, Q579*, Y339*, V39F, G491E, A464E and G360D) in our cohort and yielded 111 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2 mmol/L. Patients with two SLC5A2 variants had lower RTG (3.9 vs 6.2 mmol/L) and higher 24-h urinary glucose excretion (24hUG) than single-variant carriers (291.0 vs 40.0 mmol/1.73 m2). Patients with homozygous missense or in-frame indels had mean 24hUG of 457.2 mmol/1.73 m2, comparable to those with homozygous truncating variants (445.0 mmol/1.73 m2) and significantly more than those with homozygous splicing variants (196.6 mmol/1.73 m2). Patients with homozygous missense variants involving conservative residues (582.0 mmol/1.73 m2) had more 24hUG than those with variants at non-conservative residues (257.6 mmol/1.73 m2). Four out of 14 tested patients had mild aminoaciduria. The RTG of FRG patients had no significant correlation to phosphate reabsorption but a potential negative correlation to the fractional excretion of uric acid. Postprandial suppression of glucagon secretion was absent in most FRG patients. Conclusions: We built a comprehensive map showing the impact of SLC5A2 variant type and variant location on glucosuria severity. Our results highlighted the role of key residues in maintaining the transport function of SGLT2 and the functional link between glucosuria and reabsorption of amino acid and uric acid in FRG patients.

Novel 4.18 Mb deletion resulting in 2q37 microdeletion syndrome combined with PTH resistance found in one Chinese patient.

BACKGROUND: 2q37 microdeletion syndrome is a rare clinical condition characterized by a series of physical abnormalities. Its Albright hereditary osteodystrophy (AHO)-like manifestations and possible complication of biochemical abnormalities indicating PTH resistance greatly increased the likelihood of misdiagnosis with classic pseudohypoparathyroidism (PHP) caused by GNAS mutation or methylation alteration, even though there have only been six reports of such clinical occasions. PURPOSE: to investigate the underlying genetic defect in a male patient presenting hypocalcemia, elevated PTH and with a history of kyphosis. METHOD: clinical information was collected, while the DNA was extracted from peripheral blood and subjected to methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and exome sequencing. RESULT: Physical characteristics featuring short stature, obesity, round face, short neck, and shortened 4th metacarpal and laboratory examination of the patient suggested the presence of PTH resistance, which is indicative of PHP. MS-MLPA did not reveal methylation alterations or deletions of GNAS, STX16 or other monogenetic alterations responsible for iPPSDs, but WES revealed a long-range deletion of approximately 4.18 Mb of the 2q37 region that spanned AGAP1 to NDUFA10, indicating that the patient had 2q37 microdeletion syndrome with PTH resistance. CONCLUSION: After undergoing MS-MLPA and exome sequencing, a novel deletion spanning 4.18 Mb on the 2q37 region was identified in one male patient, clarifying the diagnosis of 2q37 microdeletion syndrome with PTH resistance. The new genetic discovery added to our understanding of the molecular defects that cause inactivating PTH/PTH-related protein signaling disorders (iPPSDs).

Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations.

ABSTRACT: Fibroblast growth factor receptor 1 (FGFR1) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l-1, follicle-stimulating hormone (FSH) levels were 1.0 IU l-1, and testosterone levels were 1.3 nmol l-1. In contrast, the de novo group had LH levels of 0.2 IU l-1, FSH levels of 0.5 IU l-1, and testosterone levels of 0.9 nmol l-1, indicating milder hypothalamus-pituitary-gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

Photodynamic therapy in periodontitis: A narrative review.

BACKGROUND: Periodontitis, a chronic infectious disease, is primarily caused by a dysbiotic microbiome, leading to the destruction of tooth-supporting tissues and tooth loss. Photodynamic therapy (PDT), which combines excitation light with photosensitizers (PS) and oxygen to produce antibacterial reactive oxygen species, is emerging as a promising adjuvant treatment for periodontitis. METHODS: This review focuses on studies examining the antibacterial effects of PDT against periodontal pathogens. It also explores the impact of PDT on various aspects of periodontal health, including periodontal immune cells, human gingival fibroblasts, gingival collagen, inflammatory mediators, cytokines in the periodontium, vascular oxidative stress, vascular behavior, and alveolar bone health. Clinical trials assessing the types of PSs and light sources used in PDT, as well as its effects on clinical and immune factors in gingival sulcus fluid and the bacterial composition of dental plaque, are discussed. RESULTS: The findings indicate that PDT is effective in reducing periodontal pathogens and improving markers of periodontal health. It has shown positive impacts on periodontal immune response, tissue integrity, and alveolar bone preservation. Clinical trials have demonstrated improvements in periodontal health and alterations in the microbial composition of dental plaque when PDT is used alongside conventional treatments. CONCLUSIONS: PDT offers a promising adjunctive treatment for periodontitis, with benefits in bacterial reduction, tissue healing, and immune modulation. This article highlights the potential of PDT in periodontal therapy and emphasizes the need for further research to refine its clinical application and efficacy.

Robust and self-lubricating polyvinyl alcohol tubes with a mucosa-like hierarchical architecture for endotracheal intubation.

Mechanical mismatch between interventional intubation tubes and human tissues often triggers inevitable friction and causes secondary injury to patients during interventional therapy. Herein, we propose a fabrication strategy of a self-lubricating polyvinyl alcohol (PVA) tube by industrial extrusion technology followed by simple infiltration with water. First, biocompatible glycerin was introduced to weaken the intrinsic hydrogen interaction of PVA by new molecular complexation, broadening the gap between the melting and decomposition temperatures and enabling the stable extrusion of the PVA tube. Subsequently, the as-prepared PVA tube was infiltrated with an aqueous solution to construct a strong hydrogen bonding network between PVA and water molecules, forming a soft hydration layer similar to the upper epithelium layer of mucosa. Benefiting from the solid and liquid properties of the hydration layer as well as the small proportion relative to the whole, the infiltrated PVA tube exhibited excellent hydration lubrication behavior and robust mechanical property. The friction coefficient, tensile strength and elongation at break were measured to be 0.05, 26.2 MPa and 654%, respectively, surpassing the values of 0.5, 16.4 MPa and 240% observed in a commercial polyvinyl chloride tube. In vitro, the PVA intubation tube demonstrated significant biocompatibility, and short-term exposure exhibited minimal impacts on the morphology and proliferation of L929 cells. Ultimately, the potential of the infiltrated PVA tube for interventional intubation was demonstrated successfully using an in vivo rabbit model, providing a new idea for the follow-up development of interventional intubation tubes.

The genetic spectrum of a Chinese series of patients with 46, XY disorders of the sex development.

PURPOSE: The etiology of 46, XY disorders of sex development (46, XY DSD) is complex, and studies have shown that different series of patients with 46, XY DSD has different genetic spectrum. In this study, we aimed to investigate the underlying genetic etiology in a Chinese series of patients with 46, XY DSD by whole exome sequencing (WES). METHODS: Seventy patients with 46, XY DSD were enrolled from the Peking Union Medical College Hospital (Beijing, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for WES to find the patients' rare variants (RVs) of genes related to 46, XY DSD. The clinical significance of the RVs was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: A total of 57 RVs from nine genes were identified in 56 patients with 46, XY DSD, which include 21 novel RVs and 36 recurrent RVs. Based on the American ACMG guidelines, 43 variants were classified as pathogenic(P) or likely pathogenic (LP) variants and 14 variants were defined as variants of uncertain significance (VUS). P or LP variants were identified in 64.3% (45/70) patients of the series. Thirty-nine, 14, and 4 RVs were involved in the process of androgen synthesis and action, testicular determination and developmental process, and syndromic 46, XY DSD, respectively. The top three genes most frequently affected to cause 46, XY DSD were AR, SRD5A2, and NR5A1. Seven patients were found harboring RVs of the 46, XY DSD pathogenic genes identified in recent years, namely DHX37 in four patients, MYRF in two patients, and PPP2R3C in one patient. CONCLUSION: We identified 21 novel RVs of nine genes, which extended the genetic spectrum of 46, XY DSD pathogenic variants. Our study showed that 60% of the patients were caused by AR, SRD5A2 or NR5A1 P/LP variants. Therefore, polymerase chain reaction (PCR) amplification and Sanger sequencing of these three genes could be performed first to identify the pathogeny of the patients. For those patients whose pathogenic variants had not been found, whole-exome sequencing could be helpful in determining the etiology.

Mixed hypogonadism: a neglected combined form of hypogonadism.

PURPOSE: Kallmann syndrome is a rare disease characterized by delayed puberty, infertility and anosmia. We report the clinical and genetic characteristics of three patients with Kallmann syndrome who presented with Klinefelter syndrome and defined this neglected combined form of hypogonadism as mixed hypogonadism. METHODS: Clinical data and examinations were obtained, including laboratory examination and magnetic resonance imagination (MRI) of the olfactory structures. Congenital hypogonadotropic hypogonadism (CHH) related genes were screened by next generation sequencing (NGS). RESULTS: Three patients with Kallmann syndrome were included. They had co-existence with Klinefelter syndrome and showed hypogonadotropic hypogonadism. Patient 1 was complicated with germinoma. CONCLUSION: Mixed hypogonadism was defined as hypogonadotropic hypogonadism in Klinefelter syndrome or primary testicular disease. Clinicians should be alert to mixed hypogonadism when spermatogenesis induction failed in patients with CHH or gonadotropin levels decrease in patients with Klinefelter syndrome.

Pulsatile Gonadotropin-Releasing Hormone Therapy Is Associated With Better Spermatogenic Outcomes than Gonadotropin Therapy in Patients With Pituitary Stalk Interruption Syndrome.

OBJECTIVE: To compare the effects of combined gonadotropin and pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). METHODS: Male patients with PSIS (N = 119) were retrospectively studied. Patients received pulsatile GnRH therapy (N = 59) were divided into response and poor-response groups based on luteinizing hormone (LH) levels after 1-month treatment with a cutoff value of 1 or 2 IU/L. Participants with gonadotropin therapy were divided into human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) group (N = 60), and patients with pulsatile GnRH therapy were classified into GnRH group (N = 28) with treatment duration ≥6 months. RESULTS: The overall success rates of spermatogenesis for hMG/hCG and GnRH therapy were 51.67% (31/60) vs 33.90% (20/59), respectively. GnRH group required a shorter period to induce spermatogenesis (8 vs 15 months, P = .019). hMG/hCG group had higher median total testosterone than GnRH group [2.16, interquartile range(IQR) 1.06-4.89 vs 1.31, IQR 0.21-2.26 ng/mL, P = .004]. GnRH therapy had a beneficial effect on spermatogenesis compared to hMG/hCG therapy (hazard ratio 1.97, 95% confidence interval 1.08-3.57, P = .026). In patients with pulsatile GnRH therapy, compared with the poor-response group, the response group had a higher successful spermatogenesis rate (5.00% vs 48.72%, P = .002) and higher median basal total testosterone (0.00, IQR 0.00-0.03 vs 0.04, IQR 0.00-0.16 ng/mL, P = .026) with LH = 1 IU/L as the cutoff value after 1-month pulsatile GnRH therapy. CONCLUSIONS: Pulsatile GnRH therapy was superior to hMG/hCG therapy for spermatogenesis in patients with PSIS. Earlier spermatogenesis and higher concentrations of sperm could be obtained in the GnRH group if patients received therapy over 6 months.

Application status of risk assessment models for periodontal disease / 口腔疾病防治

@#Risk assessment models for periodontal disease provide dentists with a precise and consolidated evaluation of the prognosis of periodontitis, enabling the formulation of personalized treatment plans. Periodontal risk assessment systems have been widely applied in clinical practice and research. The application fields of periodontal risk assessment systems vary based on the distinctions between clinical periodontal parameters and risk factors. The assessment models listed below are commonly used in clinical practice, including the periodontal risk calculator (PRC), which is an individual-based periodontal risk assessment tool that collects both periodontal and systemic information for prediction; the periodontal assessment tool (PAT), which allows for quantitative differentiation of stages of periodontal disease; the periodontal risk assessment (PRA) and modified periodontal risk assessment (mPRA), which are easy to use; and the classification and regression trees (CART), which assess the periodontal prognosis based on a single affected tooth. Additionally, there are orthodontic-periodontal combined risk assessment systems and implant periapical risk assessment systems tailored for patients needing multidisciplinary treatment. This review focuses on the current application status of periodontal risk assessment systems.

In vitro functional study of fifteen SRD5A2 variants found in Chinese patients and the relation between the SRD5A2 genotypes and phenotypes.

The 5α-reductase type 2 (5α-RD2) deficiency is one of the most common etiology of 46, XY disorders of sex development and is caused by pathogenic variants in SRD5A2. Massively parallel sequencing contributes to identification of numerous novel SRD5A2 variants, in vitro functional study could help to determine their pathogenicity. In this study, we aim to present the functional study of fifteen SRD5A2 variants found in Chinese patients and explore the genotype-phenotype association. We collected the clinical manifestation and genotype of 38 patients with 5α-RD2 deficiency who visited our center between 2009 and 2021. The pathogenicity of seven missense SRD5A2 variants, were predicted by in-silico tools. Furthermore, fifteen SRD5A2 variants without reported functional assay were studied in vitro to analyze the role of these variants in enzymatic activity. Twenty-four SRD5A2 rare variants were identified in 38 patients with 5α-RD2 deficiency. Fifteen variants without reported functional assay decreased the conversation of testosterone (T) to dihydrotestosterone(DHT) and caused the almost complete loss of enzyme activity (<8 %) in our in-vitro functional study. Thirty-eight patients with three different external genital phenotypes (complete female, clitoromegaly and hypospadias) were found to have same variants. Patients with different testicular position (scrotum/clitoris and cryptorchidism) were found to have same variants. Our study showed 15 SRD5A2 variants caused complete loss of 5α-RD2 enzyme activity by functional study. Patients with different clinical phenotypes can have the same genotypes and no obvious genotype-phenotype association exist in our series patients.

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.