BACKGROUND:Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress.Resveratrol has anti-inflammatory and anti-oxidative stress biological effects,and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE:To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into control group,model group,low-dose resveratrol group,and high-dose resveratrol group,with 10 rats in each group.Knee osteoarthritis models were established in the model group,low-dose resveratrol group,and high-dose resveratrol group.A mixture of 4%papain solution and 0.3 mol/L cysteine solution(1:1 for 0.5 hours;20 μL)was injected at 1,4,and 7 days after modeling.Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling,while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity.After 28 days of treatment,the maximum knee joint activity was measured;the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA;the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining;the degree of arthritic lesions was analyzed using the Mankin histological score;and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION:Compared with the model group,the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups,and were significantly higher in the high-dose group than the low-dose group(P<0.05).Compared with the model group,the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups.The level of malondialdehyde significantly decreased in both resveratrol groups,and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group(P<0.05).Compared with the model group,the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β,interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats,and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group(P<0.05).Compared with the model group,the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups,and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group(P<0.05).Compared with the model group,the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups,while the level of acetylated FOXO1 significantly decreased(P<0.05).The magnitude of changes was significantly better in the high-dose group than the low-dose group.To conclude,resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner,possibly through the SIRT1/FOXO1 pathway.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Postoperative pain, a common problem in perioperative management, has negative impact on patients' experience and functional recovery. The development of postoperative pain is not only related to direct surgical trauma, but also a series of preventable perioperative risk factors, among which perioperative sleep quality should not be neglected. In recent years, more and more researches have indicated that poor perioperative sleep quality is a risk factor for both acute and chronic postoperative pain, and some researches have even pointed out that sleep quality can directly influence patients' pain threshold. Therefore, this review aims to summarize current research progress on the influence of perioperative sleep quality on postoperative pain, hoping to provide reference for improving the perioperative pain management for patients.

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.

ObjectiveTo systematically collect， analyze， and evaluate the randomized controlled trials （RCT） of Chinese patent medicine combined with western medicine in the treatment of hypertension， map the evidence， and provide reference for the future clinical research and formulation of guidelines and policies. MethodThe relevant articles were retrieved from China Biology Medicine disc， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， PubMed， Embase， and Cochrane Library with the time interval from inception to December 31， 2022. The RCT of Chinese patent medicines combined with western medicine in the treatment of hypertension were included. The research characteristics and methodological quality were analyzed and evaluated. ResultA total of 330 RCTs of treating hypertension with Chinese patent medicines combined with Western medicine were included in this study， all of which were published in Chinese. These RCTs involved 88 Chinese patent medicines and 37 788 patients， and 46% of RCT had the sample size ≥100 patients. Eighty-seven percent of RCT showed the study period within 3 months. All the interventions in the RCTs were Chinese patent medicine + western medicine vs western medicine. Among the evaluation indicators， blood pressure， response rate， TCM syndrome score， endothelial cell function， and safety were mainly concerned. In terms of methodological quality， most articles did not mention the generation of random sequences， allocation concealment， or blinding method. The blinding evaluation of outcomes showed low risks of bias， and there was insufficient information to judge whether there was selective bias or other bias. ConclusionThere were many Chinese patent medicines used in combination with western medicine in the treatment of hypertension， and they were mainly taken orally. The existing RCT had problems such as small sample size， unclear clinical value positioning， imperfect design failing to reflect the value of Chinese patent medicines， unreasonable measurement indicators， and non-standard measurement methods. Future research should solve the above problems， improve the research quality， value， and authenticity， and enhance the reliability and extension of evidence.

Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

Objective:To construct standard strains representing the main epidemic clades of HIV-1 in China, amplify the virus strains, and establish a seed lot.Methods:Six isolates of HIV-1 virus were identified and analyzed in genotype and phenotype, according to " interpretation for the social organization of the Standard strains of pathogenic microorganism- technical specifications for establishment of HIV strains". The isolates were amplified and cultivated to generate the secondary generation primary seed lot and the third generation working seed lot as frozen storage in liquid nitrogen. Results:Six HIV-1 standard strains were obtained, of which 3 strains are CRF_ 07BC (NRPC2.4.9003, NRPC2.4.9005, NRPC2.4.9006), 1 strain is CRF_ 01AE (NRPC2.4.9001), 1 strain is CRF_ 08BC (NRPC2.4.9002), and 1 strain is URF (NRPC2.4.9004). Phenotypic detection showed that all six strains are CCR5 tropics and Non syncytia inducing virus. TCID 50 were all greater than 1 × 10 5/ml, and concentrations of p24 antigen were all higher than 2 ng/ml. A primary seed lot with no less than 20 vials per strain and a working seed lot with no less than 50 vials per strain were constructed. The standard virus strains were used in evaluating antiviral drugs PEG2kC34, PEG5kC34, LP-19, and neutralizing antibody LSEVh LS-F. Conclusions:Six standard strains of HIV-1 virus covering the three main epidemic subtypes of HIV-1 in China have been obtained, and a storage of HIV-1 standard strain was constructed. It meets the need of the preservation of HIV-1 standard strains in China and provides support for drug and vaccine evaluation.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Objective:To explore the effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β 1 (TGF-β 1)/Smad signaling pathway. Methods:The experimental research method was adopted. Six New Zealand white rabbits, male or female, aged 3-5 months were used and 5 full-thickness skin defect wounds were made on the ventral surface of each rabbit ear. The appearance of all rabbit ear wounds was observed on post surgery day (PSD) 0 (immediately), 7, 14, 21, and 28. On PSD 28, the scar formation rate was calculated. Three mature scars in the left ear of each rabbit were included in tension group and the arch was continuously expanded with a spiral expander. Three mature scars in the right ear of each rabbit were included in sham tension group and only the spiral expander was sutured without expansion. There were 18 scars in each group. After mechanical tension treatment (hereinafter referred to as treatment) for 40 days, the color and texture of scar tissue in the two groups were observed. On treatment day 40, the scar elevation index (SEI) was observed and calculated; the histology was observed after hematoxylin eosin staining, and the collagen morphology was observed after Masson staining; mRNA expressions of TGF-β 1, Smad3, collagen Ⅰ, collagen Ⅲ, and α-smooth muscle actin (α-SMA) in scar tissue were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction; and the protein expressions of TGF-β 1, collagen Ⅰ, collagen Ⅲ, and α-SMA, and phosphorylation level of Smad3 in scar tissue were detected by Western blotting. The number of samples of each group in the experiments was 3. Data were statistically analyzed with independent sample t test. Results:On PSD 0, 5 fresh wounds were formed on all the rabbit ears; on PSD 7, the wounds were scabbed; on PSD 14, most of the wounds were epithelialized; on PSD 21, all the wounds were epithelialized; on PSD 28, obvious hypertrophic scars were formed. The scar formation rate was 75% (45/60) on PSD 28. On treatment day 40, the scar tissue of rabbit ears in tension group was more prominent than that in sham tension group, the scar tissue was harder and the color was more ruddy; the SEI of the scar tissue of rabbit ears in tension group (2.02±0.08) was significantly higher than 1.70±0.08 in sham tension group ( t=5.07, P<0.01). On treatment day 40, compared with those in sham tension group, the stratum corneum of scar tissue became thicker, and a large number of new capillaries, inflammatory cells, and fibroblasts were observed in the dermis, and collagen was more disordered, with nodular or swirling distribution in the scar tissue of rabbit ears in tension group. On treatment day 40, the mRNA expressions of TGF-β 1, Smad3, collagen Ⅰ, collagen Ⅲ, and α-SMA in the scar tissue of rabbit ears in tension group were respectively 1.81±0.25, 5.71±0.82, 7.86±0.56, 4.35±0.28, and 5.89±0.47, which were significantly higher than 1.00±0.08, 1.00±0.12, 1.00±0.13, 1.00±0.14, and 1.00±0.14 in sham tension group (with t values of 5.36, 9.82, 20.60, 18.26, and 17.13, respectively, all P<0.01); the protein expressions of TGF-β 1, collagen Ⅰ, collagen Ⅲ, and α-SMA, and phosphorylation level of Smad3 in the scar tissue of rabbit ears in tension group were respectively 0.865±0.050, 0.895±0.042, 0.972±0.027, 1.012±0.057, and 0.968±0.087, which were significantly higher than 0.657±0.050, 0.271±0.029, 0.631±0.027, 0.418±0.023, and 0.511±0.035 in sham tension group (with t values of 5.08, 21.27, 15.55, 16.70, and 8.40, respectively, all P<0.01). Conclusions:Mechanical tension can inhibit the regression of hypertrophic scars in rabbit ears through stimulating the hyperplasia of scars, inhibiting the normal arrangement of dermal collagen fibers, and intensifying the deposition of collagen fibers, and the mechanism may be related to the activation of TGF-β 1/Smad signaling pathway by mechanical tension.