As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Background Acne treatment cycle lasts long and will cause facial appearance damage.Many patients are prone to psychological problems and severe patients may even experience suicidal ideation.However,the influencing factors of psychological health problems in acne patients are still unclear.Objective To investigate the mental health status of patients with moderate-to-severe acne and to analyze the influencing factors of their psychological health problems,so as to provide references for improving their mental health.Methods A total of 120 patients with moderate-to-severe acne of grades II-IV were selected as the research subjects,who were treated in the dermatology outpatient department of the Third Hospital of Mianyang from June 2021 to June 2023.All subjects were evaluated by using the Acne-Specific Quality of Life Questionnaire(Acne-QoL),Self-rating Depression Scale(SDS),Self-rating Anxiety Scale(SAS),Rosenberg Self-Esteem Scale(RSES)and Social Phobia Inventory(SPIN).According to the evaluation results of SDS,SAS,RSES,SPIN,subjects were divided into a group with mental health problems(n=21)and a group without mental health problems(n=99).Binary Logistic regression anaylsis was adopted to explore the influencing factors of psychological health problems in acne patients.Results A total of 21 patients(17.50%)were detected to have symptoms of depression,anxiety,inferiority or social dysfunction.Statistically significant difference was observed in comparison between two groups in gender,profession,acne classification,dietary habit,age,illness course as well as the factor scores of self perception,emotional function,social function and acne symptom in Acne-QoL(χ2=7.013,23.123,9.028,11.327,t=9.913,13.022,4.081,5.383,5.361,10.203,P<0.05).The results of binary Logistic regression analysis showed that the followings were risk factors for the occurrence of psychological health problems in acne patients:female(OR=2.243,95%CI:1.136～4.429),acne of grade III(OR=3.615,95%CI:1.269～10.295)or IV(OR=1.872,95%CI:1.073～3.266),course of disease≥1.6 years(OR=2.499,95%CI:1.068～5.851),a spicy or greasy diet(OR=3.811,95%CI:1.169～12.427),Acne-QoL self perception score≤18(OR=1.802,95%CI:1.227～2.646),Acne-QoL emotional function score≤18(OR=2.252,95%CI:1.016～4.992),Acne-QoL social function score≤14(OR=3.515,95%CI:1.534～8.053)and Acne-QoL acne symptom score≤18(OR=3.586,95%CI:1.098～11.715).Protective factors for psychological health problems in acne patients included age over 30 years old(OR=0.429,95%CI:0.283～0.648),occupation as professional cadre or enterprise employee(OR=0.483,95%CI:0.249～0.939)and other occupations(OR=0.276,95%CI:0.090～0.850).Conclusion A part of patients with moderate-to-severe acne may experience psychological health problems.Patients with female gender,higher acne grades,longer disease duration,preference for greasy or spicy foods and lower scores in all Acne-QoL factors have a higher risk of experiencing psychological health problems.

Objective: To evaluate the effect of Wendler Glottoplasty to elevate vocal pitch in transgender women. Methods: The voice parameters of pre-and 3-month post-surgery of 29 transgender women who underwent Wendler Glottoplasty in department of otorhinolaryngology head and neck surgery of Beijing Friendship Hospital from January, 2017 to October, 2020 were retrospectively analyzed. The 29 transgender women ranged in age from 19-47 (27.0±6.3) years old. Subjective evaluation was performed using Transsexual Voice Questionnaire for Male to Female (TVQ^MtF). Objective parameters included fundamental frequency (F₀), highest pitch, lowest pitch, habitual volume, Jitter, Shimmer, maximal phonation time (MPT), noise to harmonic ratio (NHR) and formants frequencies(F1, F2, F3, F4). SPSS 25.0 software was used for statistically analysis. Results: Three months after surgery, the score of TVQ^MtF was significantly decreased [(89.9±14.7) vs. (50.4±13.6), t=11.49, P<0.001]. The F₀ was significantly elevated [(152.7±23.3) Hz vs. (207.7±45.9) Hz, t=-6.03, P<0.001]. Frequencies of F1, F2 and F3 were significantly elevated. No statistical difference was observed in the frequencies of F4. The highest pitch was not significantly altered while the lowest pitch was significantly elevated [(96.8±17.7) Hz vs. (120.0±28.9) Hz, t=-3.71, P=0.001]. Habitual speech volume was significantly increased [(60.0±5.2) dB vs. (63.6±9.6) dB, t=-2.12, P=0.043]. Jitter, Shimmer, NHR and MPT were not obviously altered (P>0.05). Conclusions: Wendler Glottoplasty could notably elevate the vocal pitch, formants frequencies and degree of vocal femininity in transgender women without affecting phonation ability and voice quality. It can be an effective treatment modality for voice feminization.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Transgender Persons ; Retrospective Studies ; Speech Acoustics ; Voice Quality ; Phonation

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.
Medicine, Tibetan Traditional ; Reproducibility of Results

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ²=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×10⁹/L, 7.8 (6.3, 10.0)×10⁹ vs. 10.0 (8.3, 12.8)×10⁹/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ²=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.
Female ; Humans ; Leukocyte Count ; Male ; Nutrition Assessment ; Nutritional Status ; Retrospective Studies ; Tuberculosis, Meningeal/diagnosis*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro, and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.
Animals ; Apoptosis ; Cell Line, Tumor ; Humans ; Male ; Mannose ; Membrane Potential, Mitochondrial ; Mice ; Mitochondria ; Prostatic Neoplasms ; Reactive Oxygen Species

On the basis of literatures and standards relating to Tibetan medicine, the varieties, origin, standards and efficacy of Saxifragaceae plant used in Tibetan medicine were summarized. According to the findings, 75 species(including varieties) in 8 genera of Saxifragaceae plants, involving 21 varieties, are used in Tibetan medicine. Among them, 9 commonly used varieties, namely Songdi, Sedi, Yajima, Aoledansaierbao, Jiansidawu, Saiguo, Katuer, Sangdi, Maoqinghong, are recorded in Chinese Pharmacopoeia, Ministry Standards for Tibetan Medicine, Tibetan Medicine Standards and other local standards, accounting for 42.9% of the total number of varieties. Tibetan names, Tibetan translation of Chinese names, as well as original plant of Tibetan medicine varieties are quite different in relevant Tibetan medicine standards and literatures, which resulted in common phenomena of synonym and homonym. The standards of most varieties only involve characters, and microscopic, physical and chemical identification, with low quality standards. Based on the results of the analysis, this paper suggests strengthening surveys on herbal textual research, resources and current utilization of Saxifragaceae plants used in Tibetan medicine, summarizing the varieties, establishing improved quality standards, and perfor-ming a comparative study on therapeutic material basis and biological activity of different original plants, in order to promote rational use of these medicinal plant resources, and ensuring the accuracy, safety, and effectiveness of clinical medication.
Asian Continental Ancestry Group ; Drugs, Chinese Herbal ; Humans ; Medicine, Tibetan Traditional ; Plants, Medicinal ; Reference Standards ; Saxifragaceae

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).