Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection.

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.

[Clinical outcomes of reverse shoulder arthroplasty for the treatment of failed fixation of proximal humeral fracrtures in the elderly patients].

OBJECTIVE: To evaluate the clinical outcomes of reverse total shoulder arthroplasty as a revision procedure for the failed fixation of proximal humeral fractures in the elderly patients. METHODS: A retrospective analysis was performed on 8 patients with failed internal fixation of proximal humeral fractures from May 2014 to March 2020, including 3 males and 5 females, aged from 65 to 75 years old. All 8 patients underwent reverse total shoulder arthroplasty, and the mean time between initial fixation and reverse total shoulder arthroplasty ranged from 8 to 16 months. Range of motion(ROM), University of California at Los Angeles(UCLA) shoulder score, visual analogue scale (VAS), self-rating anxiety scale(SAS), and Constant-Murley score of shoulder function were assessed pre-operatively and at the last follow-up. Complications relating to the surgery were recorded. RESULTS: All 8 patients successfully followed up. The mean follow-up after reverse total shoulder arhroplasty ranged from 16 to 28 months. The range of motion (forward flexion, external rotation, abduction and internal rotation) of the affected shoulder was significantly improved after surgery, and the post-operative VAS, SAS and UCLA scores were also significantly improved. For the Constant-Murley score of shoulder joint function, the total scores and the subscores of pain, daily activities, range of motion and strength test at the last follow-up were all significantly improved. Scapular glenoid notch was observed in patient, which was evaluated as grade 1 on imaging. All the other patients did not develop specific or non-specific complications. CONCLUSION: Reverse total shoulder arhroplasty is an appropriate treatment as a revision surgery for failed fixation of proximal humeral fractures. It has shown satisfactory clinical outcomes, accelerating the rehabilitation of shoulder function and improving the quality of life.

[Intervention strategy based on Caprini risk assessment model and its clinical effect in preventing deep vein thrombosis after total hip replacement].

OBJECTIVE: To analyze clinical effect of intervention strategies based on Caprini thrombosis risk assessment model for preventing deep vein thrombosis (DVT) after total hip replacement (THR). METHODS: From January 2018 to December 2021, 197 patients with THR were selected as retrospective cohort study subjects, including 114 males and 83 females, aged from 45 to 80 years with an average of (66.81±10.34) years old. Caprini thrombosis risk assessment model introduced in May 2019 was used as boundary and divided into two groups, 94 patients were performed routine intervention strategies(control group) and 103 patients were received intervention strategies based on Caprini thrombosis risk assessment model (observation group). Incidence of DVT, visual analogue scale (VAS), circumference difference of affected limb, serum D-dimer (D-D) level and Harris score of hip function between two groups were analyzed. RESULTS: One-hundred and ninty-seven patients were followed up from 1 to 3 months with an average of (2.57±0.31) months. Incidence of DVT was 1.94% in observation group and 11.70% in control group, and there was statistical difference between two groups (χ2=6.642, P=0.010). VAS scores between two groups decreased gradually (P<0.001). There was significant difference between two groups in VAS score on the 1st, 2nd, 3rd and 7th day after operation (P<0.05), but no difference between two groups on the 10th day after operation (P>0.05). Difference in circumference of the affected limb between two groups after operation was gradually reduced (P<0.001), and the difference in circumference of the affected limb between two groups was statistically significant on the 1st, 2nd, 3rd, 7th, and 10th day after operation(P<0.05). Levels of serum D-D between two groups were gradually decreased after operation(P<0.05), and differences in serum D-D levels between two groups on the 8th, 24th, 48th, and 72th hour after operation were statistically significant (P<0.05). Pain score and Harris total scores between two groups were significantly increased as tomes goes on(P<0.001), no difference in VAS at 3 months after discharge, and there were statistically significant differences in Harris scores between two groups immediately after discharge, 1 month and 3 months after discharge (P<0.001). CONCLUSION: Intervention strategy based on Caprini thrombosis risk assessment model could reduce incidence of DVT in patients with THR, improve postoperative pain and swelling of the affected limb, and promote recovery of hip joint function.

Persistence of Antibody and Cellular Immune Responses in Coronavirus Disease 2019 Patients Over Nine Months After Infection.

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.

Chondroprotective Effect of Wufu Decoction on Tumor Necrosis Factor-α-Induced Chondrocytes via the Extracellular Signal Regulated Kinase 1/2 Signaling Pathway.

OBJECTIVE: Wufu Decoction (WFD) is a herbal formulation composed of five traditional Chinese herbs that is used clinically for arthritis treatment in China. The current study investigated the chondroprotective effects and the underlying mechanism of WFD for osteoarthritis (OA) therapy. METHODS: The chondroprotective effects of WFD were investigated based on vitro study. Following the successful isolation of chondrocytes from rat cartilage tissues and the identification of collagen II expression with immunofluorescence staining, chondrocytes were co-incubated with tumor necrosis factor-α (TNF-α) to induce an inflammation model; WFD was also administered. After the treatment, cell viability was determined by MTT assay, cell apoptosis was assessed by DAPI staining, the concentration of inflammation cytokines interleukin (IL)-1ß and IL-6 were detected with ELISA assay, the expression of collagen II, MEK1/2-ERK1/2 signaling pathway proteins was detected using western blotting, and mRNA expression of MMP-1, MMP-9 and MMP-13 were determined with quantitative real-time polymerase chain reaction. RESULTS: Wufu Decoction significantly restored the cell viability suppressed by TNF-α and inhibited the cell apoptosis induced by TNF-α in chondrocytes. The high concentrations of IL-1ß and IL-6 in TNF-α-induced model cells were significantly decreased in WFD-treated chondrocytes, and the immunofluorescence staining and western blot results showed that the inhibited expression of collagen II in the TNF-α-induced model group was significantly increased in WFD-treated chondrocytes. The protein expressions of MEK1/2, p-ERK1/2, and P53 were significantly reduced in the WFD-treated group compared with those in the model group, and the mRNA expressions of MMP-1, MMP-9, and MMP-13 were also significantly reduced with WFD treatment. CONCLUSION: The present study indicated that WFD exerted a chondroprotective effect in TNF-α-induced chondrocytes via the regulation of the ERK1/2 signaling pathway, suggesting that WFD has therapeutic potential for OA therapy.

Relationships between traditional larval indices and meteorological factors with the adult density of Aedes albopictus captured by BG-mosquito trap.

OBJECTIVES: Larval indices have been used for Ae. albopictus surveillance for many years, while there is limited use in assessing dengue transmission risk and adult mosquito emergence. This study is aimed to explore the relationships between larval indices and the Ae. albopictus density captured by BG-mosquito trap (BG-trap) method, with considering the meteorological factors. METHODS: Data on larval density, adult mosquito density and meteorology factors were collected in an entomological survey carried out in Quzhou City, Zhejiang Province of China in 2018. The Spearman's rank correlation and Pearson correlation were used for the analysis on the correlation of density indices. Generalized additive models were established to analyze the influencing factors of mosquito density. RESULTS: Breteau index (BI), House index (HI) and Container index (CI) were highly correlated with each other (r>0.7, p<0.05). The Ae. albopictus density was significantly correlated with CI (rs = 0.260, p<0.05), CI pre one week (rs = 0.259, p<0.05), and CI pre three weeks (rs = 0.329, p<0.05). BI was correlated with female Ae. albopictus density pre 4 weeks (r = -0.299, p<0.05). Female Ae. albopictus density was correlated with CI pre 3 weeks (rs = 0.303, p<0.05). The influencing factors of BI were average wind speed pre 1 week, average temperature and female Ae. albopictus density pre 4 weeks. The influencing factors of CI were average humidity pre 3 weeks and average temperature. The influencing factors of HI were average temperature and precipitation pre 4 weeks. The influencing factor of Ae. albopictus density and female Ae. albopictus density was temperature. CONCLUSIONS: The adult Ae. albopictus density had low correlation with certain larval indices. Some of the meteorology factors played significant roles in the density of adult Ae. albopictus and larva with or without a time lag.

[High strength wire under arthroscopy combined with outside anchor nail in treating Meyers McKeever II, III avulsion fracture of anterior cruciate ligament tibial check point].

OBJECTIVE: To explore clinical effect of high strength wire under arthroscopy combined with outside anchor nail in treating Meyers McKeever II, III anterior cruciate ligament tibial check point. METHODS: From March 2014 to June 2016, 21 patients with Meyers McKeever II, III avulsion fracture of anterior cruciate ligament tibial check point were treated by high strength wire under arthroscopy combined outside anchor nail. There were 13 males and 8 females aged from 18 to 48 years old with an average of (26.40±5.42) years old. There were 9 cases injured on the left side, and 12 cases on the right side. The courses of disease included sports injuries of 12 cases, falling down injuries of 6 cases, and accident injuries of 3 cases. According to Meyers-McKeever classification, 16 patients were type II and 5 patients were type III. All fractures were fresh, closed and simple injury. The time from injury to operation ranged from 2 to 15 days with an average of (6.20±2.63) d. Lysholm score, IKDC score and the changes of knee mobility were observed and compared before operation and 6 months after operation. RESULTS: Twenty-one patients were followed up for 12 to 24 months with an average of (14.30±3.01) months. Operation time ranged from 40 to 65 min with an average of (45.10±4.82) min, Blood loss ranged from 5 to 15 ml with an average of (10.05±2.75) ml. Lysholm score was improved from 50.29±6.67 before operation to 92.48±2.18 at 6 months after operation. IKDC scores was increased from 47.19±4.57 before operation to 90.71±2.22 at 6 months after operation. Knee joint activity was respectively (83.05±5.33)° and (132.05±7.15)° before operation and 6 months after operation. CONCLUSIONS: High strength wire under arthroscopy combined outside anchor nail in treating Meyers McKeever II, III ACL tibial check point has the advantages of less trauma, firm fixation, and satisfactory clinical effect.

[Reverse total shoulder arthroplasty for the treatment of old fracture of proximal humerus in elderly patients].

OBJECTIVE: To investigate clinical results of reverse total shoulder arthroplasty in treating old fracture of proximal humerus in elderly patients. METHODS: From January 2012 to December 2017, 12 elderly patients with old proximal humeral fractures were treated with reverse total shoulder arthroplasty. There were 5 males and 7 females with an average age of 70.2 years old (ranged from 63 to 81 years old) and an average course of 12.3 months (ranged from 9 to 18 months). VAS score was used to evaluate the degree of pain relief of shoulder joint, Constant-Murley score was used to evaluate the improvement of shoulder joint function and observe the complications during and after operation. RESULTS: All the 12 patients were followed up with an average duration of 22.3 months (ranged from 15 to 56 months). At the latest follow-up, the VAS score was 1.9±1.4, and Constant-Murley score was 83.4±8.4. Among them, shoulder joint flexion was (92.5±7.7)°, abduction was (90.4±14.3)°, external rotation was(31.9±10.0)°, and internal rotation was(58.9±13.1)°. There was statistical significance before and after treatment(P<0.05). There were 2 cases with glenoid notch. The imaging findings were grade I and grade II respectively. No loosening was found during follow-up. No infection, acromial fracture, prosthesis loosening, axillary nerve injury and other complications occurred. CONCLUSIONS: Reverse total shoulder arthroplasty in treating old proximal humeral fractures in elderly patients can achieve satisfactory results, however, indications and complications should be noted.

Anxiolytic and neuroprotective effects of the Traditional Chinese Medicinal formulation Dan-zhi-xiao-yao-san in a rat model of chronic stress.

Dan-zhi-xiao-yao-san is a Traditional Chinese Medicinal formulation widely used for the treatment of neuropsychological disorders. The present study examined the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san in a rat model of chronic stress. The results of an elevated plus maze test showed that Dan­zhi­xiao­yao­san significantly attenuated the levels of anxiety-induced stress as evidenced by increases in the time spent in the open arm region, as well as the percentage of entries into this area. In addition, Dan-zhi-xiao-yao-san alleviated stress­induced neuronal death, as indicated by histological examination. Furthermore, mechanistic studies suggested that the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san may be mediated via attenuation of chronic stress­induced upregulation of α­synuclein and corticosterone, and downregulation of protein phosphatase 2A (PP2A) in the hippocampal region of the brain at the mRNA and protein level. In addition, Dan­zhi­xiao­yao­san decreased the serum levels of stress­induced corticosterone in the model animals. In conclusion, the present study demonstrated that Dan­zhi­xiao­yao­san exerted anxiolytic and neuroprotective effects in a rat model of chronic stress via attenuation of stress­induced upregulation of α­synuclein and corticosterone, and downregulation of PP2A in the hippocampus.

Nosocomial transmission of avian influenza A (H7N9) virus in China: epidemiological investigation.

STUDY QUESTION: Can avian influenza A (H7N9) virus be transmitted between unrelated individuals in a hospital setting? METHODS: An epidemiological investigation looked at two patients who shared a hospital ward in February 2015, in Quzhou, Zhejiang Province, China. Samples from the patients, close contacts, and local environments were examined by real time reverse transcriptase (rRT) polymerase chain reaction (PCR) and viral culture. Haemagglutination inhibition and microneutralisation assays were used to detect specific antibodies to the viruses. Primary outcomes were clinical data, infection source tracing, phylogenetic tree analysis, and serological results. STUDY ANSWER AND LIMITATIONS: A 49 year old man (index patient) became ill seven days after visiting a live poultry market. A 57 year old man (second patient), with a history of chronic obstructive pulmonary disease, developed influenza-like symptoms after sharing the same hospital ward as the index patient for five days. The second patient had not visited any poultry markets nor had any contact with poultry or birds within 15 days before the onset of illness. H7N9 virus was identified in the two patients, who both later died. Genome sequences of the virus isolated from both patients were nearly identical, and genetically similar to the virus isolated from the live poultry market. No specific antibodies were detected among 38 close contacts. Transmission between the patients remains unclear, owing to the lack of samples collected from their shared hospital ward. Although several environmental swabs were positive for H7N9 by rRT-PCR, no virus was cultured. Owing to delayed diagnosis and frequent hospital transfers, no serum samples were collected from the patients, and antibodies to H7N9 viruses could not be tested. WHAT THIS STUDY ADDS: Nosocomial H7N9 transmission might be possible between two unrelated individuals. Surveillance on patients with influenza-like illness in hospitals as well as chickens in live poultry markets should be enhanced to monitor transmissibility and pathogenicity of the virus. FUNDING, COMPETING INTERESTS, DATA SHARING: Funding support from the Program of International Science and Technology Cooperation of China (2013DFA30800), Basic Work on Special Program for Science and Technology Research (2013FY114600), National Natural Science Foundation of China (81402730), Special Program for Prevention and Control of Infectious Diseases in China (2013ZX10004218), US National Institutes of Health (1R01-AI108993), Zhejiang Province Major Science and Technology Program (2014C03039), and Quzhou Science and Technology Program (20111084). The authors declare no other interests and have no additional data.

Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells.

Previous studies have revealed that high levels of serum homocysteine (Hcy) are closely associated with the development of juvenile and age-related cataracts. An increased concentration of Hcy is likely to induce gene specific demethylation in DNA promoter regions. The aim of the present study was to prevent this demethylation by administering acetyl-l-carnitine (ALCAR) to human lens epithelial cells (HLECs). Different concentrations of Hcy were used to treat HLECs for 3, 6, 12 and 24 h and the findings were used to determine the optimum dose to induce endoplasmic reticulum (ER) stress. Similarly, the concentration of ALCAR was standardized. The production of reactive oxygen species (ROS) and the percentage of cells undergoing cell death were measured. The levels of antioxidants, ER stress-associated proteins, mRNA levels of nuclear factor erythroid-2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and promoter DNA methylation of the Keap1 gene were also assessed. Hcy was observed to induce ER stress, produce ROS and lead to cell death. However, administration of ALCAR prevented these effects to a significant degree. Additionally, western blot analysis revealed that ALCAR increased the levels of antioxidant proteins, including catalase, superoxide dismutase, glutathione peroxidase, Nrf2, Keap1 and glutathione. Similarly, the reverse transcription-quantitative polymerase chain reaction experiments on Nrf2 and Keap1, as well as the bisulfite genomic DNA sequencing analysis revealed a preventive effect of ALCAR against Hcy-induced ER stress. The ER stress-induced activation of the unfolded protein response is responsible for demethylation of Keap1 promoter DNA to activate the expression of the Keap1 protein, which then increases the targeting of Nrf2 for proteosomal degradation. This decrease in Nrf2 activity represses the transcription of numerous antioxidant enzyme genes and alters the redox-balance towards lens oxidation. However, treatment with ALCAR led to significant protection from these effects. The present results suggested that ALCAR either prevents or ameliorates the actions of the antioxidant system in HLECs at the level of the protein and the gene. Further advanced studies are required for the development of ALCAR as an anti-cataract agent.

Isometric reconstruction of the posterolateral corner of the knee.

To date, there is no consensus on the best technique to repair injured posterolateral structures of the knee. We evaluated the effects of a fibular head based isometric reconstruction of the posterolateral knee corner with a double bundle semitendinosus tendon. From February 2001 to February 2005, 18 isometric reconstructions of a chronic posterolateral corner (PLC) injury of the knee were performed using the semitendinosus tendon. The average age of the patients was 39 years, ranging from 19 to 52 years. Twelve were male and 6 female. The time interval between injury and treatment ranged from 1.5 to 14 months. Three patients had simple PLC injuries, 10 had combined PLC-posterior cruciate ligament (PCL) injuries and two of them had undergone a PCL reconstruction elsewhere 6.5 months prior to referral. Three other patients had an associated anterior cruciate ligament (ACL) injury and two had a combination of PLC with ACL and PCL injury. A doubled semitendinosus tendon was threaded through bony tunnels in the fibular head running from the insertion of the lateral collateral ligament (LCL) to the fibular insertion of the popliteo-fibular ligament and both ends were fixed proximally into bony tunnels of the lateral femoral condyle at their respective isometric point. The varus stress test and the posterolateral rotation test were used to evaluate stability of the posterolateral structures. Isometry was optimal between the femoral attachment site of the popliteal tendon to the anatomical insertion of the popliteofibular ligament at the fibular head. The fibular insertion of the LCL is isometric to the anterior or antero-inferior 8-10 mm of the femoral insertion of the LCL. The average follow-up period was 32 months (30-42 months). There was no varus knee instability in full extension. At 30 degrees of flexion two cases demonstrated a grade I varus instability. A fibular head based isometric reconstruction is a reproducible and reliable technique for reconstruction of the posterolateral corner of the knee.