Objective:To systematically evaluate the efficacy, patient-reported outcomes (PROs) and safety of hyaluronic acid (HA) fillers and collagen stimulators (PCL/PLLA) for various facial aesthetic indications.Methods:This study focused on facial fillers approved and widely used in China, including HA fillers such as Juvéderm?, Restylane?, Belotero?, Fillmed?, and PCL/PLLA such as Ellansé?, L?viselle?, and CureWhite?. A systematic literature search was conducted across both English and Chinese databases, including PubMed, Cochrane Library, Embase, CNKI, and Wanfang Data, covering the period from database inception to August 24, 2023, to identify randomized controlled trials (RCTs). The characteristics and outcomes of the included RCTs were summarized and analyzed, including efficacy indicators by injection site, patient satisfaction, and safety profiles. Network meta-analysis (NMA) was performed using R software to compare efficacy outcomes, including the 6-month improvement response rate for nasolabial folds (NLF) and the global aesthetic improvement scale (GAIS).Results:A total of 38 articles were included. Among them, Juvéderm? was most frequently used as the treatment group (17 out of 38 articles), while Restylane? was the most common comparator (17 out of 38 articles), particularly in studies involving NLF injections (15 out of 16 articles). For collagen stimulators, only 2 studies on Ellansé? were included, both focusing solely on NLF treatment. Quality assessment showed that 34 studies were of medium to high quality, with Juvéderm? accounting for the majority of high-quality studies (11 articles). Based on injection sites, NLF was the most studied area (16 articles), followed by the midface (8 articles), and the remaining 14 articles covered other regions including lips, nose, chin, and infraorbital area. In the NLF region, the 6-month improvement response rate assessed by blinded investigators showed that Juvéderm? showed better outcomes than Restylane? ( RR=1.07, 95% CI: 0.89-1.32), while Belotero? was slightly inferior to Restylane? ( RR=0.97, 95% CI: 0.65-1.44), although the differences were not statistically significant. Subject-reported outcomes showed consistent trends with investigator assessments. For 6-month GAIS improvement, Juvéderm? and Restylane? showed comparable result within the HA filler category ( RR=1.01, 95% CI: 0.71-1.43). The collagen stimulator Ellansé? demonstrated numerically higher values than HA fillers ( RR=1.32, 95% CI: 0.86-2.08). However, none of these differences reached statistical significance. In midface treatments, Juvéderm? had more long-term evidence, with follow-up periods extending up to 24 months. Four studies reported numerically greater volume enhancement with Juvéderm? compared to Restylane?. For other facial areas, Juvéderm? had the most comprehensive clinical evidence, covering the widest range of injection sites. No relevant RCTs were available for collagen stimulators in these regions. Regarding patient satisfaction, 19 studies reported patient-reported outcomes, with Juvéderm? contributing 16 of them, and showing higher satisfaction in 6 head-to-head comparisons with Restylane?. In contrast, collagen stimulators currently lack such evidence. Safety result indicated that HA fillers were generally safe and well tolerated, while safety data for collagen stimulators remain limited due to insufficient high-quality evidence. Conclusion:Among the HA fillers, Juvéderm? has a large quantity and highest quality of clinical studies, and NMA result shows its superior efficacy in NLF. In comparison, the current evidence is still not sufficient to draw a clear conclusion for the PCL/PLLA due to a lack of adequate high-quality clinical evidence regarding its clinical efficacy, PROs, and safety.

Pain modulation encompasses a complex neurobiological process, in which the lateral habenula (LHb) plays a crucial role in integrating, regulating and modulating pain signals. It is also involved in pain-related memory functions associated with perception, transmission and regulation of pain. Furthermore, the LHb collaborates with structures such as the spinal dorsal horn, forebrain, and amygdala to form an essential neural circuit that contributes to sensitization, development of tolerance, and adaptation processes related to pain. However, there remains limited understanding regarding the specific roles and interactions among different neuron subtypes within the LHb concerning pain regulation. Additionally, further investigation is warranted to explore functional changes and plasticity within both the LHb and its associated neural circuits in chronic pain models. Future research endeavors should utilize advanced neuroimaging techniques alongside optogenetics and gene editing technologies to elucidate intricate neural circuits, cellular architecture, and molecular mechanisms governing LHb function in pain regulation. In conclusion, this paper aims to comprehensively review existing literature on the involvement of the LHb and its neural circuits in modulating pain, thereby enhancing our understanding of their neurobiological mechanisms while providing novel targets for precise therapeutic strategies aimed at alleviating pain.

Pain modulation encompasses a complex neurobiological process, in which the lateral habenula (LHb) plays a crucial role in integrating, regulating and modulating pain signals. It is also involved in pain-related memory functions associated with perception, transmission and regulation of pain. Furthermore, the LHb collaborates with structures such as the spinal dorsal horn, forebrain, and amygdala to form an essential neural circuit that contributes to sensitization, development of tolerance, and adaptation processes related to pain. However, there remains limited understanding regarding the specific roles and interactions among different neuron subtypes within the LHb concerning pain regulation. Additionally, further investigation is warranted to explore functional changes and plasticity within both the LHb and its associated neural circuits in chronic pain models. Future research endeavors should utilize advanced neuroimaging techniques alongside optogenetics and gene editing technologies to elucidate intricate neural circuits, cellular architecture, and molecular mechanisms governing LHb function in pain regulation. In conclusion, this paper aims to comprehensively review existing literature on the involvement of the LHb and its neural circuits in modulating pain, thereby enhancing our understanding of their neurobiological mechanisms while providing novel targets for precise therapeutic strategies aimed at alleviating pain.

Objective:To systematically evaluate the efficacy, patient-reported outcomes (PROs) and safety of hyaluronic acid (HA) fillers and collagen stimulators (PCL/PLLA) for various facial aesthetic indications.Methods:This study focused on facial fillers approved and widely used in China, including HA fillers such as Juvéderm?, Restylane?, Belotero?, Fillmed?, and PCL/PLLA such as Ellansé?, L?viselle?, and CureWhite?. A systematic literature search was conducted across both English and Chinese databases, including PubMed, Cochrane Library, Embase, CNKI, and Wanfang Data, covering the period from database inception to August 24, 2023, to identify randomized controlled trials (RCTs). The characteristics and outcomes of the included RCTs were summarized and analyzed, including efficacy indicators by injection site, patient satisfaction, and safety profiles. Network meta-analysis (NMA) was performed using R software to compare efficacy outcomes, including the 6-month improvement response rate for nasolabial folds (NLF) and the global aesthetic improvement scale (GAIS).Results:A total of 38 articles were included. Among them, Juvéderm? was most frequently used as the treatment group (17 out of 38 articles), while Restylane? was the most common comparator (17 out of 38 articles), particularly in studies involving NLF injections (15 out of 16 articles). For collagen stimulators, only 2 studies on Ellansé? were included, both focusing solely on NLF treatment. Quality assessment showed that 34 studies were of medium to high quality, with Juvéderm? accounting for the majority of high-quality studies (11 articles). Based on injection sites, NLF was the most studied area (16 articles), followed by the midface (8 articles), and the remaining 14 articles covered other regions including lips, nose, chin, and infraorbital area. In the NLF region, the 6-month improvement response rate assessed by blinded investigators showed that Juvéderm? showed better outcomes than Restylane? ( RR=1.07, 95% CI: 0.89-1.32), while Belotero? was slightly inferior to Restylane? ( RR=0.97, 95% CI: 0.65-1.44), although the differences were not statistically significant. Subject-reported outcomes showed consistent trends with investigator assessments. For 6-month GAIS improvement, Juvéderm? and Restylane? showed comparable result within the HA filler category ( RR=1.01, 95% CI: 0.71-1.43). The collagen stimulator Ellansé? demonstrated numerically higher values than HA fillers ( RR=1.32, 95% CI: 0.86-2.08). However, none of these differences reached statistical significance. In midface treatments, Juvéderm? had more long-term evidence, with follow-up periods extending up to 24 months. Four studies reported numerically greater volume enhancement with Juvéderm? compared to Restylane?. For other facial areas, Juvéderm? had the most comprehensive clinical evidence, covering the widest range of injection sites. No relevant RCTs were available for collagen stimulators in these regions. Regarding patient satisfaction, 19 studies reported patient-reported outcomes, with Juvéderm? contributing 16 of them, and showing higher satisfaction in 6 head-to-head comparisons with Restylane?. In contrast, collagen stimulators currently lack such evidence. Safety result indicated that HA fillers were generally safe and well tolerated, while safety data for collagen stimulators remain limited due to insufficient high-quality evidence. Conclusion:Among the HA fillers, Juvéderm? has a large quantity and highest quality of clinical studies, and NMA result shows its superior efficacy in NLF. In comparison, the current evidence is still not sufficient to draw a clear conclusion for the PCL/PLLA due to a lack of adequate high-quality clinical evidence regarding its clinical efficacy, PROs, and safety.

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.
Sialic Acid Binding Immunoglobulin-like Lectins/metabolism* ; N-Acetylneuraminic Acid ; Immunoglobulins/metabolism* ; Receptors, Immunologic ; Ligands

Objective: To monitor the antimicrobial resistance and drug-resistance genes of Yersinia enterocolitis, Y. intermedia and Y. frederiksenii recovered from retailed fresh poultry of 4 provinces of China. Methods: The susceptibility of 25 isolated Yersinia spp. to 14 classes and 25 kinds of antibiotics was determined by broth microdilution method according to CLSI (Clinical and Laboratory Standards Institute). The antibiotic resistance genes were predicted with antibiotic resistance genes database (ARDB) using whole genome sequences of Yersinia spp. Results: In all 22 Y. enterocolitis tested, 63.7% (14 isolates), 22.8% (5 isolates), 4.6% and 4.6% of 1 isolates exhibited the resistance to cefoxitin, ampicillin-sulbactam, nitrofurantoin and trimethoprim-sulfamethoxazole, respectively. All the 25 isolates were multi-drug resistant to more than 3 antibiotics, while 64.0% of isolates were resistant to more than 4 antibiotics. A few Y. enterocolitis isolates of this study were intermediate to ceftriaxone and ciprofloxacin. Most Yersinia spp. isolates contained antibiotic resistance genes mdtG, ksgA, bacA, blaA, rosAB and acrB, and 5 isolates recovered from fresh chicken also contained dfrA1, catB2 and ant3ia. Conclusion The multi-drug resistant Yersinia spp. isolated from retailed fresh poultry is very serious in the 4 provinces of China, and their contained many kinds of drug-resistance genes.

Objective To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations,and to explore the relationship among genotypes,clinical manifestations and immunophenotypes.Methods Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology,Children's Hospital of Fudan University between October 2013 and June 2017.The data included clinical manifestations,immunophenotypes and genotypes.Results A total of 8 patients were diagnosed with RAG1 deficiency (6 boys and 2 girls).The minimum age of onset was 2 months,and the maximum age was 4 months.The minimum age of diagnosis was 2 months,and the maximum age was 13 years.Four patients had a family history of infant death due to severe infections.Two cases were born to the same consanguineous parents.All cases had recurrent infections,including involvement of respiratory tract (8 cases),digestive tract (6 cases),urinary tract (1 case),and central nervous system (1 case).The pathogens of infection included bacteria,viruses and fungi.Rotavirus was found in 3 cases,cytomegalovirus (CMV) in 5 cases,bacillus Calmette-Guérin adverse reaction in 2 cases (1 of whom had a positive acid-fast smear from lymph node puncture fluid),fungal infection in 3 cases.One case had multiple nodular space-occupying lesions in lungs and abdominal cavity complicated with multiple bone destruction.The peripheral blood lymphocyte counts of all patients ranged between 0.1 × 109/L and 3.3 × 109/L (median,0.65 × 109/L).Eosinophilia was found in 3 cases (range,(0.48-1.69) x 109/L).The patients were classified according to immunophenotype as severe combined immunodeficiency phenotype (4 cases),leaky severe combined immunodeficiency (2 cases),Omenn syndrome (1 case) and combined immunodeficiency(1 case).Decreased serum IgG levels were found in 3 cases,increased serum IgM levels in 3 cases,increased serum IgE levels in 5 cases.RAG1 homozygous mutations were detected in 5 cases and RAG1 compound heterozygous mutations in 3 cases.Two novel mutations and six previously reported mutations were identified.Three cases were successfully treated with hematopoietic stem cell transplantation.Four cases died due to infections,and the 13 year-old patient was still under follow-up in the outpatient clinic.Conclusions Different RAG1 gene mutations can lead to diverse clinical presentations and immune phenotypes.Clinicians should pay attention to the family history of infant death with severe infection.In that situation,immunological evaluation and gene detection should be performed as early as possible.

ObjectiveTo explore the influences of perceived social support and social evaluations( including trust in others,government and social organizations,satisfaction of the government and social organizations,and satisfaction with the disaster relief and reconstruction work)on disaster area adults'life satisfaction after the Yushu earthquake.MethodsWith perceived social support scale (PSSS),satisfaction with life scale (SWLS) and self made survey,370 Tibetan adults were investigated,and the average age was 32.99 ± 12.66.Results ①Perceived fricnds' support( r =0.24,P ＜ 0.01 ),perceived others＇ support ( r =0.15,P ＜ 0.01 ),trust in others,government and social organizations ( r =0.19,P ＜ 0.01 ),satisfaction with the government and social organizations ( r =0.14,P ＜ 0.05) and satisfaction with the disaster relief and reconstruction work ( r=0.17,P ＜ 0.01 )had significant positive correlations with Yushu adults'life satisfaction.②Perceived friends' support ( β =0.21,P ＜ 0.01 )and trust in others,government and social organizations(β =0.27,P＜0.05) were significant predictors of Yushu adults'life satisfaction.ConclusionPerceived friends'support and trust in others,government and social organizations can play an important role in Yushu adults'life satisfaction after the earthquake.

Objeetive To investigate the optimized concentration,effectiveness and histological change of Pingyangmycin by local injection of keloids for two weeks.Methods The appropriate concentration was analyzed,based on the Vancouver scar scale.48 eases of keloids were randomly divided into 4 groups with different concentrations of Pingyangmycin (1,0.5,0.25,and 0.125 mg/ml).Each case was iniected for five times at two weeks intervals,and then the statistical results (pair t test) and the histological changes were evaluated.Results Statistically,0.5 mg/ml group was more effective (P=0.0026),and this group had significant differences from the others (SNK test).The rate of the recurrence for one year was 12.00% in the whole effective cases.The keloid tissue after treatments,histologically,showed the thicker epidermis and larger papillary layer of the dermis,more inflammatory cells.Conclusions 0.5 mg/ml Pingyangmycin is the most appropriate concentration in this study and 0.25 mg/ml is the effective one.This treatment for keloid is convenient,safe,effective,low recrudescence and few side effects.

BACKGROUND: Recently, one focus of research has been Annexin Ⅴ (AnV) existing on hepatic cells membranes as a fundamental receptor related to hepatitis B virus (HBV) infection. Also its expression in placental tissues has been a matter of debate. The study of the relationships between placental cells infected with HBV and their AnV expression will be of great value in future prevention strategies and treatments.OBJECTIVE: To investigate the presence of AnV in HBV infected human's placental cells and its potential role in HBV intrauterine transmission.DESIGN: Randomized controlled experiment.SETTING: Taishan Medical College.MATERIALS: Placental tissue was collected from HBsAg positive full term pregnant women (30 cases) admitted to Jinan Institute for Maternal and Child Health, Taian Central Hospital and Taian Institute for Maternal and Child Health from January 2003 to December 2004. Maternal serum was also obtained. Informed consents for participating in this study were obtained from all the involved pregnant women and this experiment was approved by the Hospital Ethics Committee. Rabbit-anti-human AnV purified affinity antibody (first antibody), rat-anti-human HBs mAb (first antibody),and biotinylated goat-anti-mouse IgG (secondary antibody) were supplied by Wuhan Boster Bioengineering Company.METHODS: Using SABC immunohistochemical staining reagent, 18 HBsAg positive placentas were obtained from 30HBsAg infected patients in full term pregnancy. These were considered as the positive group and the other 12 were used as negative controls. The staining process included dewaxing, dehydration of embedded slides and microwave antigen restoration. In the wet box, rabbit-anti-human AnV purified antibody (first antibody, 1:60, monoclonal antibody)was added on the slides and kept at 4 ℃ overnight. Rat-anti-human antibody HBs mAb(secondary antibody, 1:50) was added and kept at 4 ℃ ovemight, after this procedure, biotinylated goat-anti-mouse IgG(1:100), the first fluorescent antibody such as FITC-goat anti-rabbit IgG (1:50) and the second fluorescent antibody (Avidin-Cy3) were used,respectively. The slides were sealed with buffered glycerol and examined under a confocal laser scanning microscope.The images on the slides were analyzed with IPP 4.5 image programs.MAIN OUTCOME MEASURES: Detecting the simultaneous existence and distribution of HBsAg/AnV in placental cells with HBV infection.RESULTS: Ten cases from the positive group were simultaneously detected for HBsAg/AnV by double-labeled immunofluorenscence assay and confocal laser scanning microscope. AnV expression was detected in the trophoblastic, interstitial cells and vascular endothelial cells of villi interstitial blood vessels, and the coexistence of HBsAg/AnV was found even in one cell.CONCLUSION: HBsAg combined with the receptor AnV in the same placental cells is a common finding in HBV infected full term pregnant women. This finding is very suggestive of a mechanism where AnV could promote hepatitis B virus to enter the placental cells and cause intrauterine infection.