UNASSIGNED: to compare the results of using Dapoxetine and HA (hyaluronic acid) gel injection by Five puncture technique in the treatment of premature ejaculation (PE).
UNASSIGNED: 100 sexually active heterosexuals circumcised males with lifelong PE were included in the study. Group A patients were treated with on-demand Dapoxetine, while group B was treated with HA gel glans penis injection using a five-puncture technique. Both groups were evaluated at 1st,3rd and 6th months post-treatment using IELT.
UNASSIGNED: There were no significant differences between both groups regarding patient demographic. Mean pretreatment IELT in groups A and B were 45.82 ± 7.44 and 46.18 ± 7.82 receptively. There was no significant difference between both groups. After treatment, both groups show significant ILET improvement during the 1st,3rd, and 6th months follow-up with a P value < 0.001. However, when comparing the improvement of ILET in group A (Dapoxetine) and group B (HA injection), there were high significance differences in favor of group B in the 1st,3rd, and 6th-month follow-up.
UNASSIGNED: Although both treatment modalities have improved IELT and premature ejaculation, but HA injection with five punctures technique was significantly better than oral Dapoxetine with self-limited side effects.

This study aimed to investigate the effects of 0.6% hyaluronic acid (HA) gel on the healing process and postoperative pain levels after diode laser-assisted labial frenectomy in pediatric patients. Ninety-six pediatric patients (females, 50 and males, 46) aged 8-14 years were randomly divided into four groups as follows: (1) conventional frenectomy with 0.6% topically administered HA (CFH, n = 24); (2) conventional frenectomy with placebo gel (CFP, n = 24); (3) frenectomy performed by diode laser with 0.6% topically administered HA (DLH, n = 24); and (4) frenectomy performed by diode laser with placebo gel (DLP, n = 24). HA application was continued for 1 week thrice daily after the frenectomy. Visual analog scale forms were collected from patients 1 week after the operation. In addition, the plaque index, gingival index, periodontal probing depth, and keratinized tissue width and thickness were recorded. This process was repeated 1 and 3 months after the first visit. The DLH group revealed significant differences in the probing depth, bleeding on probing, keratinized gingiva width, and attached gingiva width according to dual comparisons of the initial, first, and third-month values (p = 0.010, p = 0.007, p<0.001, and p = 0.001, respectively). Significant differences were observed between the CFP and CFH groups according to the initial and initial third-month values with regard to the bleeding on probing (p=0.019 and p = 0.019, respectively). The attached gingival thickness revealed significant differences between the CFP and CFH groups for the initial and initial-third-month comparisons (p = 0.005 and p = 0.007, respectively). The mean values of the initial and initial-third-month differences were significantly higher in the CFH group than those in the CFP group. HA- and laser-assisted labial frenectomies revealed better outcomes in terms of the probing depth, attached gingiva width, keratinized gingiva width, healing process, and postoperative comfort.

Intrauterine adhesion (IUA) is primarily caused by endometrial injury, and hysteroscopic adhesiolysis is presently the main treatment. However, postoperative recurrence and poor pregnancy outcomes remain intractable. In this study, we aim to assess the effects of different treatments on clinical symptoms and reproductive outcomes in IUA. This retrospective study was conducted in a tertiary university-affiliated women\'s hospital. The study included 1449 consecutive women who desired to have a baby and were diagnosed with IUA through hysteroscopy from January 2016 to December 2021. Patients with IUA underwent hysteroscopic electric resection (E) or cold scissors separation (C), as well as hormone therapy and one or both of the following secondary prevention measures: intrauterine devices (IUD) and hyaluronic acid gel (HA). The pregnancy rate (PR) was significantly higher in the E + IUD + HA (90.23% CI: 85.82, 94.64%) than in other groups (p = 0.000) groups. The rates of full-term birth (p = 0.000) and live birth (p = 0.000) were significantly higher in the E + IUD + HA (67.82% and 68.97%, respectively) and E + HA (62.41% and 63.91%, respectively) groups. Multivariate logistic regression analysis revealed a significantly higher PR in women who received second-look hysteroscopy (OR 1.571, 95% CI: 1.009-2.224, p = 0.013) and E + IUD + HA (OR 4.772, 95% CI: 2.534-8.987, p = 0.000). Combining hysteroscopic electric resection with IUDs and HA gel could prevent adhesion recurrence and improve postoperative pregnancy and live birth outcomes in IUA. Furthermore, postoperative second-look hysteroscopy may increase the PR and shorten the waiting period.

BACKGROUND: Injectable hyaluronic acid (HA) gel has emerged as a widely used soft tissue filler for surgeries. In penile reconstructive surgery, HA gel has been employed for penile or glans augmentation in selected patients diagnosed with micropenis. This augmentation technique involves injecting the gel into submucosal tissue and increasing the size of the penis for approximately 1 year. A few studies have investigated the possible complications correlated with medically assisted penile injections of HA gel. However, no previous reports have shown the complications of self-administered HA injection. This case report aims to present the first documented case of ischaemic priapism as a complication of self-administered HA injection.
METHODS: We present the case of a 43-year-old male who self-administered a 20 mL injection of HA into the dorsal side of his penis. The injected material probably reached the corpora cavernosa, leading to priapism within a few hours. However, the patient did not seek medical attention until 72 h later. The first two initial conservative attempts of blood drainage were unsuccessful because the gel had obstructed vein drainage, causing the penis to remain in a state of priapism. The final treatment approach involved shunting, high enoxaparin doses and oral Effortil administration.
CONCLUSIONS: While complications from medically assisted HA injections have been documented, this case report sheds light on the complications arising from self-administered penile injections. Priapism is a severe medical condition that requires immediate treatment to avoid potentially serious long-term consequences. Healthcare providers and patients must acknowledge its symptoms and its appropriate course of treatment, especially in the context of penile medical injections.

Surgical gingivectomy can be considered the gold standard treatment for gingival enlargement. The healing of wound site after gingivectomy occurs slowly by secondary intention. To accelerate the wound healing process, several studies have been conducted evaluating the effect of various treatment modalities. Photobiomodulation therapy (PBMT) was proposed to provide minimally invasive and painless treatment as well as to decrease discomfort of the patient following the surgical process. Another factor that is expected to improve the healing after surgery is topical application of chemotherapeutic agents such as Hyaluronic acid (HA). This study aims to assess the effect of topically applied HA gel after PBMT on the healing of wound site after surgical gingivectomy.
This randomized controlled clinical trial included twenty-six surgical gingivectomy wound sites, equally divided into two groups, Group-I (test group): the surgical sites after gingivectomy were irradiated with a diode laser (980 nm, 0.2 W) then covered by 2% HA gel loaded in a special custom-made soft transparent tissue guard appliance for each patient. Group II (control group): the surgical sites were irradiated with a diode laser (980 nm, 0.2 W) only. Wound healing was assessed subjectively by Landry healing index on the 3rd, 7th, 14th and 21st days after surgery, and pain perception was assessed by the patients using visual analog scale (VAS) throughout the 21 days of the follow up period. Comparisons between the two study groups were performed using Mann-Whitney U test, while comparisons between different time points were performed using Friedman test. Significance was inferred at p value < 0.05.
By the end of the follow-up period, surgical sites of the test group showed excellent healing compared to the control group. There were no significant differences in VAS scores between both groups (p > 0.05).
Application of 2% HA gel as an adjunctive to PBMT was found to have significant clinical effects and higher power of repair among test group when compared to that achieved by PBMT alone in control group.
This study was retrospectively registered on ClinicalTrials.gov and first posted on 28th of March 2023 with an identifier number: NCT05787912.

Diabetic foot ulcer (DFU) is a main diabetic complication with unmet treatment needs. This study applied human umbilical cord-derived mesenchymal stem cells-hyaluronic acid (hucMSCs-HA) gel to treat DFU in a noninvasive external way and investigated its paracrine action and mechanism. In this study, after analyzing the physical and biological properties of HA gel, hucMSCs-HA gel was applied in 2 in vivo models (types I and II DFU), and a molecular mechanism was investigated. To evaluate the paracrine action of hucMSCs, hucMSCs-conditional medium (MSC-CM) was collected to treat 1 in vivo model (type I DFU) and 2 in vitro models (high glucose (HG)-injured human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs)). The results indicated that HA gel with a porous microstructure underwent over 90% degradation and swelled to the maximum value within 48 h. In vivo, hucMSCs-HA gel accelerated wound healing of DFU rats by improving re-epithelialization, collagen deposition, and angiogenesis, in which a paracrine action of hucMSCs was confirmed and the phosphorylation of p38, ERK1/2, JNK, and Akt was increased. In vitro, MSC-CM improved cell viability, wound healing, migration, tube formation, cell senescence, and abnormal expressions (TNF-α, IL-1β, IL-6, ET-1, p16 genes, and PCNA protein) of HUVECs, also improved cell viability, wound healing, antioxidant stress, and abnormal expressions (COL1, COL3, COL4, SOD1, SOD2 genes, and PCNA protein) of HSFs. Summarily, noninvasive external application of hucMSCs-HA gel shows great perspective against DFU and exerts wound healing effects through the MAPK and Akt pathways-mediated paracrine mechanism.

暂无摘要。

Proteolysis-targeting chimera (PROTAC) is an emerging technique for degrading disease-related proteins. However, the current PROTACs suffer from inadequate solubility and lack of organ targeting, which has hampered their druggability. Herein, we report direct and sustained delivery of PROTACs using microneedle patches to the diseased tissues. In this study, we use an estrogen receptor alpha (ERα)-degrading PROTAC, ERD308, to treat ER-positive breast cancer. A pH-sensitive micelle, MPEG-poly(β-amino ester) (MPEG-PAE), is used to encapsulate ERD308 along with an FDA-approved CDK4/6 inhibitor, Palbociclib (Pal), before loading into biodegradable microneedle patches. These patches enable prolonged drug release into deep tumors, maintaining therapeutic levels for at least 4 days, with an excellent drug retention rate of over 87% in tumors. ERD308 released from the microneedle patches can sufficiently degrade ERα in MCF7 cells. Co-administration of ERD308 and Palbociclib exhibits excellent efficacy by over 80% tumor reduction as well as a good safety profile. Our work demonstrates the feasibility and proof-of-concept therapeutic potential of using microneedle patches to directly deliver PROTACs into tumors.

Hyaluronic acid in its various forms shows bacteriostatic, fungistatic, anti-inflammatory, anti-edematous, osteoinductive, and pro-angiogenetic properties. This study aimed to evaluate the effect of subgingival delivery of 0.8% hyaluronic acid (HA) gel on clinical periodontal parameters, pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and biochemical markers of inflammation (C-reactive protein (CRP) and alkaline phosphatase (ALP) enzymes) in patients with periodontitis. Seventy-five patients with chronic periodontitis were divided randomly into three groups (25 in each group): group I received scaling and surface root debridement (SRD) + HA gel; group II received SRD + chlorhexidine gel; and group III received surface root debridement alone. Clinical periodontal parameter measurements and blood samples were collected to estimate pro-inflammatory and biochemical parameters at the baseline before therapy and after two months of therapy. The results show that HA gel has a significant effect on the reduction in clinical periodontal parameters (PI, GI, BOP, PPD, and CAL), IL-1 beta, TNF-alpha, CRP, and ALP after 2 months of therapy as compared to the baseline (p < 0.05) with nonsignificant differences from the CHX group (p > 0.05), except GI (p < 0.05), and significant differences from the SRD group (p < 0.05). Moreover, significant differences were found between the three groups regarding the mean improvements of GI, BOP, PPD, IL-1β, CRP, and ALP. It can be concluded that HA gel has a positive effect on clinical periodontal parameters and improvements in inflammatory mediators similar to chlorhexidine. Therefore, HA gel can be used as an adjuvant to SRD in the treatment of periodontitis.

The gut of babies born vaginally is rapidly colonized by Bifidobacterium spp. after birth, while in infants born by cesarean section (C-section), the presence of bifidobacteria drops dramatically, increasing the risk of developing gastrointestinal disorders. Considering that newborns naturally come into contact with maternal lactobacilli as they pass through the birth canal, the aim of this work is to exploit for the first time the bifidogenic activity exerted by the cell-free supernatants (CFSs) from lactobacilli of vaginal origin, belonging to the species Lactobacillus crispatus, Lactobacillus gasseri, Limosilactobacillus vaginalis, and Lactiplantibacillus plantarum. CFSs were recovered after 7 h, 13 h, and 24 h of fermentation and assessed for the ability to stimulate the planktonic growth and biofilms of Bifidobacterium strains belonging to species widely represented in the gut tract. A bifidogenic effect was observed for all CFSs; such activity was maximal for CFSs recovered in exponential phase and was strongly dependent on the species of lactobacilli. Importantly, no stimulating effects on an intestinal Escherichia coli strain were observed. CFSs from L. vaginalis BC17 showed the best bifidogenic profile since they increased bifidobacterial planktonic growth by up to 432% and biofilm formation by up to 289%. The CFS at 7 h from BC17 was successfully formulated with a hyaluronic acid-based hydrogel aimed at preventing and treating breast sores in lactating women and exerting bifidogenic activity in infants born mainly by C-section. IMPORTANCE Bifidobacteria in the gut tract of infants play crucial roles in the prevention of gastrointestinal diseases and the maturation of the immune system. Consequently, strategies to trigger a bifidogenic shift in the infant gut are highly desirable. Evidences suggest that the presence of a maternal vaginal microbiota dominated by health-promoting lactobacilli and the development of a bifidobacterium-enriched gut microbiota in newborns are interconnected. In this context, we found out that the cell-free supernatants from lactobacilli of vaginal origin were able to effectively stimulate the proliferation of Bifidobacterium spp. grown in free-floating and biofilm forms. The cell-free supernatant from Limosilactobacillus vaginalis BC17 showed excellent bifidogenic behavior, which was preserved even after its incorporation into a nipple formulation for lactating women. Lactobacilli derivatives, such as cell-free supernatants, have gained increasing interest by virtue of their safer profile than that of living cells and can be proposed as an ecosustainable approach to favor gut colonization of infants by bifidobacteria.