Volume 100 ·  Issue 32 ·  2020

To explore the relationship between family with sequence similarity 13 member A (FAM13A) gene and small airway remodeling in chronic obstructive pulmonary disease (COPD), and the effect of interference with FAM13A gene expression on the apoptosis and proliferation phenotype of human airway epithelial cells (16HBE).

From January 2018 to January 2020, 74 patients in the Department of Thoracic Surgery of General Hospital of Ningxia Medical University were treated by surgery for lung tumors or pulmonary bullae. According to the lung function and smoking history, the 74 patients were divided into four groups: non-smoking group with normal lung function (normal group, 23 patients), smoking group with normal lung function (smoking group, 24 patients), non-smoking group with COPD (11 patients) and smoking group with COPD (16 patients). The expression of FAM13A in small airway of each group was detected by immunohistochemistry, and the correlation between FAM13A and the airflow restriction indexes by pulmonary function was analyzed. The shRNA fragment of FAM13A gene was designed, and the shRNA lentivirus vector of FAM13A gene was constructed and packaged. The expression level of FAM13A gene was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blot, and the best shRNA sequence was screened. Flow cytometry was used to detect apoptosis rate and the fluorescence intensity of proliferation marker Ki-67 in 16HBE cells.

FAM13A was mainly expressed in the cytoplasm of small airway epithelial cells. The levels of FAM13A absorbance (A) of small airway epithelial cells in non-smoking group and smoking group with COPD were higher than those in normal group and smoking group (0.365±0.026, 0.412±0.053 to 0.113±0.018, 0.105±0.009, all P<0.05), and they were negatively correlated with forced expiratory volume in 1s/forced vital capacity (FEV₁/FVC) and FEV₁% pre (r=-0.48 and r=-0.40, all P<0.05). The FAM13A shRNA lentiviral vector was successfully constructed, and FAM13A interference was successfully achieved in the 16HBE cell line. After infection of 16HBE cells, the results of qRT-PCR and Western blot showed that the expression of FAM13A in shRNA-target-2 group decreased (all P<0.01). Compared with the negative control group (shRNA-NC), the apoptosis rate of FAM13A shRNA group decreased (P=0.023), and the fluorescence intensity of Ki-67 also decreased (P=0.042).

FAM13A gene expression is increased in COPD small airway epithelial cells, and it is related to COPD airflow limitation. FAM13A gene may participate in the process of COPD remodeling by affecting the apoptosis and proliferation of human airway epithelial cells.

To evaluate the effect of renal function on sarcopenia in elderly male patients with chronic kidney disease (CKD).

A total of 105 male CKD patients aged ≥65 years who were admitted to the Chinese PLA General Hospital between October 1, 2018 and January 30, 2019 were included in this study. Using two different equations to estimate glomerular filtration rate (GFR), respectively. According to the sarcopenia criteria, the participants were categorized as the non-sarcopenia group (n=72) and the sarcopenia group (n=33), respectively. The association of estimated GFR (eGFR) and the sarcopenia in the male CKD patients was analyzed using the model of multivariate logistic regression.

Among the 105 patients, the median age was 74 (68, 77) years old. The prevalence of sarcopenia was 31.4% (33/105). According to the multivariate logistic regression analysis, eGFR based on serum creatinine and Cys-C (eGFRscr-cys) lower than 45 ml·min^-1·(1.73 m²)^-1 (OR=4.17, 95%CI:1.08-16.02, P=0.038) and eGFR based on Cys-C (eGFRcys) lower than 45 ml·min^-1·(1.73 m²)^-1 (OR=3.99, 95%CI:1.08-14.75, P=0.038) were independent risk factors for underlying sarcopenic, respectively. The area under the receiver operating characteristics curve (AUC) revealed that eGFRscr-cys (AUC=0.67) was more suitable than eGFRcys (AUC=0.64) to predict the sarcopenia in elderly male patients with CKD.

The increased incidence of sarcopenia in elderly men with CKD is accompanied with deterioration of renal function.

To observe the clinical efficacy of external physical vibration lithecbole (EPVL) in the treatment of calculous renal colic under different positions.

A total of 120 calculous renal colic patients who underwent EPVL from September 2018 to September 2019, were randomly divided into three groups utilizing random number table: supine position group, the lateral position group and the hybrid position group, with 40 cases in each group. Prior to the EPVL, each patient was given an intravenous injection of 20 mg furosemide. When the patients accumulated enough urine, they began to undergo EPVL. Numeric Rating Scale (NRS) was applied to assess the pain intensity before and after the treatment. Furthermore, all the patients were examined by B-ultrasound or urinary CT a day and a week after the treatment. The NRS score, side effects, stone discharge rate, time of pain relief, and pain recurrence rate were compared among different groups.

Prior to the treatment, there was no significant difference of the pain intensity among three groups (P>0.05). After the treatment, the pain intensity considerably alleviated in all the groups. The NRS score decreased by 4.05±0.24, 3.23±0.23 and 2.90±0.21 in supine, lateral and hybrid position groups, respectively. The time of pain relief was (8.88±0.46) min, (10.33±0.44) min and (10.38±0.50) min in supine, lateral and hybrid position groups, respectively. Overall, the efficacy of lateral position group was better than the other two groups in terms of speed and degree of pain relief (P< 0.05). The total pain relief rate was 91.7%. However, the pain recurrence rate was 15.0% (6/40), 15.0% (6/40) and 12.5% (5/40) in supine, lateral and hybrid position groups, respectively, however, there was no significant difference among three groups (P>0.05). But the hybrid position group had a relatively low rate of pain recurrence. The aggregate stone discharge rate of three groups was 25.8% and 62.5% a day and a week after the treatment respectively. The calculus clearance rate of surgical day was 22.5% (9/40), 35% (14/40) and 20% (8/40) in supine, lateral and hybrid position groups, respectively. Moreover, the stone removal rate was 60% (24/40), 75% (30/40) and 52.5% (21/40) in supine, lateral and hybrid position groups, respectively. The result indicated that the supine position group had the highest stone discharge rate (P<0.05). Overall, there was no case with severe complications, and there was no significant difference of side effects among three groups (P>0.05).

EPVL can safely and effectively improve calculous renal colic and assist the removal of stone. When calculous renal colic was treated under EPVL, the patients can benefit from all three positions, and thus it is crucial to decide which position is more appropriate in different scenarios.

To investigate the clinical features of patients with biopsy-proven sarcoid uveitis.

The clinical data of the patients with biopsy-proven sarcoid uveitis who consulted the Ophthalmic Clinic of Beijing Tongren Hospital from February 2012 to February 2020 was retrospectively reviewed and analyzed. All the patients underwent visual acuity test, slit lamp microscopy, indirect ophthalmoscopy, fundus fluorescein angiography (FFA), chest computed tomography (CT) and other auxiliary examinations.

A total of 9 patients (18 eyes) (6 females, 3 males) with biopsy-proven sarcoid uveitis were included in the study, with a mean age of (52.6±9.0) years. Based on the modified Scadding classification, there were 2 and 7 cases of Stage Ⅰ and Ⅱ sarcoidosis, respectively. The ocular symptoms were the initial presenting complaints in 6 patients, who had a time from onset to diagnosis of 9.0 (2.6, 20.3) months. Three patients had a history of sarcoidosis. Fever was reported in 2 patients, fatigue in 3 patients, body weight loss in 3 patients, respiratory problems in 5 patients, with bilateral ocular involvement in all the patients. Among the 18 eyes, panuveitis occurred in 10 eyes, posterior uveitis in 4 eyes, anterior uveitis in 4 eyes, mutton fat keratic precipitates (KP) in 10 eyes, granular KP or no obvious KP in 8 eyes, posterior synechia of the iris in 9 eyes, cataract in 8 eyes, inflammatory vitreous opacity in 8 eyes, macular edema in 7 eyes, epiretinal membrane in 6 eyes, retinal vasculitis in 2 eyes, glaucoma in 2 eyes, and optic disc granuloma in 2 eye. Among the 13 eyes whose peripheral ocular fundus was visible, multiple chorioretinal peripheral lesions were found in 5 eyes.

Chest CT should be performed in the uveitis patients with older age, female gender, bilateral ocular involvement, the symptom of fever, body weight loss and respiratory problems in time to exclude the sarcoid uveitis. Sarcoid uveitis may presents with granular KP or no obvious KP, and the posterior segment of the eye ball was the most commonly involved area.

To compare the effects of vestibular rehabilitation training and drug therapy on the symptoms of vertigo and disability in patients with vestibular peripheral vertigo.

This prospective study was enrolled 43 patients with vestibular peripheral vertigo who admitted to the outpatient department of Eye & ENT Hospital of Fudan University from January 2018 to December 2018. They were randomly divided into two groups: control group (drug treatment group) and experimental group (drug treatment combined rehabilitation training group). All patients filled in the first vertigo disability rating scale (DHI), specific activity balance confidence scale (ABC) and anxiety self-rating scale (SAS) on the day of treatment and at two, four and eight weeks after treatment intervention, and the data were statistically analyzed.

There was no significant difference in gender, age and body weight between the two groups (P>0.05). After treatment (Control group (4w) : DHI (45.5±30.6) , ABC (86.9±12.4) , SAS (37.9±8.2) Experimental group (8w) : DHI (34.8±28.5) , SAS (35.7±7.9) ) , the three scales of the two groups were better than before treatment (Control group: DHI (59.2±25.9) , ABC (79.7±16.7) ,SAS (41.1±6.8) ; Experimental group: DHI (55.2±20.5) , ABC (80.3±18.3) , SAS (41.9±9.1) ) . The comparison of data before and after treatment in each group according to treatment time indicated that DHI and ABC scores in the experimental group showed that the DHI and ABC scores of the experimental group changed significantly at 2 weeks after treatment, and the SAS scores changed at 4 weeks after treatment. The difference was statistically significant (P<0.05). However, there was a statistically significant difference between the control group DHI score 4 weeks after treatment and SAS score 8 weeks after treatment (P<0.05). ABC score did not show statistical difference (P>0.05).

The subjective symptoms and anxiety of vertigo and disability in the two groups improved obviously after treatment. Compared with drug therapy alone, drug therapy combined with vestibular rehabilitation training can significantly improve patients′ subjective symptoms of vertigo and disability, as well as their anxiety and depression, so as to improve their overall quality of life.

To study the value of color doppler ultrasonography (CDU) in diagnosis of impending ruptured abdominal aortic aneurysm (IRAAA).

A total of 35 cases with IRAAA which were identified by CDU in our department from June 2014 to June 2019 were retrospectively analyzed. All the patients were detected by computed tomographic angiography (CTA). The types, length of the neck of aneurysm, largest diameter, thrombosis, involvement of common iliac artery and impending ruptured conditions were compared. The postoperative patients were followed-up by CDU and CTA (mean time was 2.6 months).

Among 35 patients, CDU diagnosed that 5 cases were pararenal types and 30 cases were infrarenal types. CTA showed that 4 cases were pararenal types and 31 cases were infrarenal types. The misdiagnosis rate of CDU was 2.9% (1/35). CDU showed that bilateral common iliac arteries were involved in 21 cases, right common iliac arteries were involved in 3 cases, and left common iliac arteries were involved in 2 cases. CTA detected the same results. There was no statistical difference between CDU and CTA for detection of the largest anteroposterior diameter, transverse diameter and the thickness of thrombosis (P values were 0.354, 0.310 and 0.865). There was statistical difference in the detection of the length of the aneurysm′s neck (P=0.006). CDU showed 3 cases of focal wall discontinuity, 4 cases of hyperattenuating crescent sign, 3 cases of thrombus fissuration and 2 cases of saclike protuberance, which were consistent with the detection of CTA. CDU showed that locally thin wall of aneurysm was detected in the rest of 23 cases. CTA showed 2 patients were negative. The misdiagnosis rate of CDU was 5.7% (2/35). Three cases did not undergo surgery. Open repairs (OR) were performed in 5 cases. Endovascular aneurysm repairs (EVAR) were performed in 27 cases. The postoperative patients were followed up by CDU and CTA at 1 month, 3 months, 6 months and 12 months. All the artificial blood vessels and stents were patent. Endoleak was observed in 5 cases. Aneurysm sac thrombosis was found in the rest of the cases.

CDU plays an important role in the analysis and diagnosis of the size, range, and the impending ruptured symptoms of the aneurysm. It provides a reliable basis for IRAAA screening, diagnosis and postoperative follow-up, and has important clinical value.

To explore the clinical features and prognosis of gastric mucosa-associated lymphoid tissue lymphoma.

The data of patients with gastric mucosa-associated lymphoid tissue lymphoma diagnosed and treated at Peking University Cancer Hospital from 2000 to 2019 were collected, and their clinical characteristics, treatment options and effects, and prognosis were retrospectively analyzed.

The median age of 68 patients was 56 years old, and the ratio of men to women was 0.6∶1.0. Early patients accounted for about 76% (52/68). The most commonly used treatment is Helicobacter pylori eradication, followed by radiotherapy and chemotherapy. The total effective rate is 94%, of which the complete remission rate is 72%. With a median follow-up of 44 months, the 5-year progression-free survival (PFS) rate was 73%, and the overall survival (OS) rate was 83%. Prognostic factor analysis showed that albumin level (P=0.011) and international prognostic index (IPI)(P=0.017) are independent prognostic indicators of PFS, The 5-year PFS rate of patients with normal and reduced albumin was 77% and 50%, respectively, and the 5-year PFS rate of patients with IPI score<2 points and IPI ≥ 2 points was 80% and 48%, respectively. Lactate dehydrogenase (LDH) (P=0.016) and albumin level (P=0.025) are independent prognostic indicators of OS, and the 5-year OS rates of patients with normal and elevated LDH were 87% and 67%, respectively. The 5-year OS rates of patients with normal albumin and reduced were 92% and 73%, respectively.

Gastric mucosa-associated lymphoid tissue lymphoma is sensitive to treatment and has a good prognosis. The patient′s albumin and lactate dehydrogenase levels are independent prognostic indicators.

To investigate the effect of stomatin protein expression on the proliferation and apoptosis of lung cancer cells.

The expressions of stomatin mRNA in human bronchial epithelial cells (HBE) and lung cancer cells (H520, A549, 95D, H460, Glc-82, 973 and H1299) were detected by Real-time PCR. Immunohistochemistry (IHC) was used to detect stomatin protein expression in 4 lung cancer tissue microarrays with 259 cases of lung cancer and adjacent normal tissues. After knocking down the expression of stomatin in A549 cells, the proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, the apoptosis was detected by flow cytometry, the expression levels of total protein kinase B (AKT) and phosphorylated AKT at Ser473 were detected by Western blot. BALB/c nude mice were used to detect the tumorigenic ability of stomatin downregulated A549 cells (3 mice) and control cells (3 mice), and the protein expressions of stomatin, Ki67 and CD31 in tumor tissues were detected by IHC.

The M (range) of stomatin mRNA expression level in H520, A549, 95D, H460, Glc-82, 973, H1299 and HBE cells were 2.71 (2.66), 3.55 (3.16), 0.26 (0.22), 2.08 (1.98), 0.87 (0.35), 1.72 (2.53), 1.10 (1.82) and 0.01 (0.02), respectively. The mRNA expression levels of stomatin in H520, A549 and H460 cells were higher than that of HBE cells (all P<0.05), whereas there was no statistical difference among 95D, Glc-82, 973, H1299 and HBE cells (all P>0.05). IHC of lung tissue microarrays showed that the positive rate of stomatin expression in human lung cancer tissues was 34.7% (90/259), which was significantly higher than that in adjacent normal tissues [1.9% (5/259)] (P<0.05). In stomatin positive lung cancer tissues, the M (IQR) of tumor size for lower stomatin expression tissues (67 cases) was [41.22 (2 761.50) cm], which was smaller than that of higher stomatin expression tissues [(23 cases, 57.98(1 333.50) cm) (P<0.05). After knocking down stomatin expression, the fourth day absorbance value of stomatin-downregulated A549 cells was 0.55±0.07, which was lower than that of control cells (0.79±0.16) (P=0.012). The proportion of early apoptotic cells of stomatin-downregulated A549 cells [8.83 (53.00)] was higher than that of control cells [4.17 (25.00)] (P=0.026). The Ser473 phosphorylated AKT protein expression level in stomatin-downregulated A549 cells was 0.68±0.16, which was decreased compared with control cells (1.16±0.39) (P<0.05). The M (IQR) of total AKT expression level in stomatin-downregulated A549 cells was 4.25 (17.00), without statistically significant difference from control cells [4.75 (19.00)] (P>0.05). After inoculation of stomatin-downregulated A549 cells in nude mice for 43 days, the tumor volume was (37.93±3.12) mm³, which was significantly smaller than that of the control group [(454.04±32.39) mm³] (P<0.001). And the expression levels of stomatin, nuclear proliferation antigen Ki67, and platelet-endothelial cell adhesion molecule CD31 were 1.78±0.69, 5.19±3.84, and 10.77±1.67, respectively, which were all decreased compared with control group (17.52±8.76, 54.14±41.02, and 19.72±6.97, respectively) (all P<0.05).

Stomatin promotes lung cancer cell proliferation and inhibits cell early apoptosis by regulating AKT signaling pathway.

To systematically evaluate the efficacy and safety of vitamin D supplementation in the treatment of pulmonary tuberculosis.

Biomedical Database was searched to collect randomized controlled trials (RCT) related to vitamin D supplementation in tuberculosis patients, and the retrieval time was from establishment to November 2019. Two evaluators independently screened the literature and extracted the data. The negative conversion rate of acid-fast-bacilli of sputum smear, the negative conversion rate of mycobacterium tuberculosis culture and the change of serum vitamin D level were the main outcome indicators, and the body mass index was the secondary outcome indicator. The incidence of hypercalcemia and abnormal urinary calcium were used as adverse event indicators and the RevMan 5.2 software was used for meta-analysis.

A total of 8 RCT_S met the inclusion criteria, including 850 patients with tuberculosis. Meta-analysis showed that compared with the control group, negative conversion rate of acid-fast-bacilli of sputum smear and serum vitamin D level increased after 8 weeks of vitamin D supplementation [RR (95%CI) and mean deviation (MD) (95%CI) were 1.06 (1.00, 1.13) and 8.81 (1.81, 15.81), respectively; negative conversion rate of acid-fast-bacilli of sputum smear was not increased at week 4 and 12 [RR (95%CI) were 1.08 (0.97, 1.20) and 1.01 (0.91, 1.12), respectively]; negative conversion rate of mycobacterium tuberculosis culture in sputum was not increased after 4 and 8 weeks [RR (95%CI) were 1.06 (0.91, 1.22) and 1.02 (0.96, 1.08), respectively]; there was no change in body mass index [MD (95%CI):-0.02 (-0.53, 0.50)]; there was increased risk of abnormal urinary calcium [RR (95%CI): 2.45 (1.75, 3.41)], while no increase in risk of hypercalcemia [RR (95%CI): 1.99 (0.96, 4.13)].

Vitamin D supplementation is safe but not effective in the treatment of pulmonary tuberculosis.

China adopted an unprecedented province-scale quarantine since January 23rd 2020, after the novel coronavirus (COVID-19) broke out in Wuhan in December 2019. Responding to the challenge of limited testing capacity, large-scale (>20 000 tests per day) standardized and fully-automated laboratory (Huo-Yan) was built as an ad-hoc measure. There is so far no empirical data or mathematical model to reveal the impact of the testing capacity improvement since quarantine.

Based on the suspected case data released by the Health Commission of Hubei Province and the daily testing data of Huo-Yan Laboratory, the impact of detection capabilities on the realization of "clearing" and "clearing the day" of supected cases was simulated by establishing a novel non-linear and competitive compartments differential model.

Without the establishment of Huo-Yan, the suspected cases would increase by 47% to 33 700, the corresponding cost of quarantine would be doubled, the turning point of the increment of suspected cases and the achievement of "daily settlement" (all newly discovered suspected cases are diagnosed according to the nucleic acid testing result) would be delayed for a whole week and 11 days. If the Huo-Yan Laboratory could ran at its full capacity, the number of suspected cases could start to decrease at least a week earlier, the peak of suspected cases would be reduced by at least 44%, and the quarantine cost could be reduced by more than 72%. Ideally, if a daily testing capacity of 10 500 tests was achieved immediately after the Hubei lockdown, "daily settlement" for all suspected cases could be achieved.

Large-scale, standardized clinical testing platform, with nucleic acid testing, high-throughput sequencing, and immunoprotein assessment capabilities, need to be implemented simultaneously in order to maximize the effect of quarantine and minimize the duration and cost of the quarantine. Such infrastructure, for both common times and emergencies, is of great significance for the early prevention and control of infectious diseases.

Colon cancer (CRC) is one of the common cancers, and metastasis is the leading cause of death. Recent studies have found that first-line chemotherapy drugs irinotecan or oxaliplatin combined with epidermal growth factor receptor (EGFR) -targeted drugs can improve the median overall survival of patients with metastatic colorectal cancer (mCRC) by more than 2 years. However, KRAS-mutated colon cancer patients (about 30% to 50%) show resistance to EGFR-targeted drugs. Therefore, EGFR-targeted drugs cannot be used to treat mCRC patients with KRAS mutations. Many previous studies have pointed out that metformin has anti-tumor effects, and taking metformin is closely related to a good prognosis of patients. However, many retrospective studies have found that metformin is not related to the prognosis of cancer patients, and there are still many questions and differences about the therapeutic effect and molecular mechanism of metformin on tumors.

To evaluate vitamin D supplementation₃Impact on mortality and tuberculosis incidence in HIV-infected individuals initiating antiretroviral therapy (ART) A vitamin D supplementation was administered to HIV-infected individuals with serum 25-hydroxyvitamin D concentrations below 30 ng/ml and initiating ART at four large HIV care and treatment centers in Dar es Salaam, Tanzania₃A randomized, double-blind, placebo-controlled trial of. Age of exclusion<18 years of age, pregnant, or participating in any other clinical trial. Subjects were randomly assigned in a 1:1 ratio to oral vitamin D during the first month of ART₃50 000 U/week, followed by vitamin D supplementation₃2 000 U/d, the control group was given placebo at the same time interval and frequency. The randomized control list was computer-generated by a non-statistical investigator with a sequence block of 10, ensuring complete assignment concealment, and subjects, field groups, and researchers were assigned in disguise. The trial was followed up for 1 year and the primary outcome measures were death and new tuberculosis in HIV-infected subjects. An intention-to-treat analysis of all-cause mortality was performed, and subjects diagnosed with tuberculosis at the time of randomization, who were receiving antituberculous therapy, or who were suspected of having tuberculosis and were later diagnosed were excluded from the study tuberculosis incidence analysis. Between 24 February 2014 and 24 February 2017, 6 250 ART-initiated adult subjects were screened for serum 25-hydroxyvitamin D, of which 4 000 subjects participated in the trial and were followed for 1 year (all subject follow-ups were completed on 7 March 2018). 2 001 subjects were randomized to vitamin D₃Group, 1 999 subjects were randomly assigned to placebo. A total of 415 subjects died, including vitamin D₃211 cases in the group and 204 cases in the placebo group were supplemented with vitamin D₃There was no statistically significant effect on the risk of death in HIV-infected persons (HR=1.04，95%CI：0.85~1.25）。 Vitamin D₃There was no statistically significant difference in the new prevalence of pulmonary tuberculosis between the group and the placebo group (HR=0.78，95%CI：0.54~1.13）。 Vitamin D₃There were 3 and 2 cases of hypercalcemia in the group and the placebo group, respectively, and vitamin D supplementation was found₃Does not increase the risk of hypercalcemia (RR=1.25，95%CI：0.43~3.66）。 For hospitalization rates, vitamin D₃There were 101 cases in the placebo group and 94 cases in the placebo group, and the difference was not statistically significant (IRR=1.06，95%CI：0.80~1.41）。

In order to understand the effects of vitamin A and D supplementation on symptom relief and sputum smear conversion time in pulmonary tuberculosis patients, a 2×2 factorial design randomized controlled trial was conducted in Qingdao, China. Symptom relief of tuberculosis patients was evaluated by TB-score including cough, expectoration, hemoptysis, dyspnea, chest pain, night hot flashes, night sweats, fatigue, anorexia, fever and body mass index. Between October 2012 and March 2015, a total of 800 patients with pulmonary tuberculosis who received standardized chemotherapy (isoniazid, rifampicin, ethambutol, pyrazinamide for February/isoniazid, rifampicin for April) were randomly assigned 1:1:1:1. 39 patients were withdrawn because they could not complete standard chemotherapy. Finally, 190 patients received standard pulmonary tuberculosis treatment only (control group), 187 patients received vitamin A supplementation (2 000 U/d), 199 patients received vitamin D supplementation (400 U/d), and 185 patients received both vitamin A (2 000 U/d) and vitamin D (400 U/d) combined supplementation were included in the symptom analysis. Finally, 761 patients were included in the tuberculosis symptom analysis. Of the 761 patients with pulmonary tuberculosis, 203 patients had negative sputum smear at baseline, 37 patients had no subsequent sputum smear results, and the remaining 521 patients were included in the sputum smear conversion analysis (128 patients in the vitamin A supplementation group, 145 patients in the vitamin D supplementation, 121 patients in the combined vitamin A and vitamin D supplementation, and 127 patients in the control groupHR=1.021，95%CI: 0.821 to 1.271), vitamin D (HR=0.949，95%CI: 0.760~1.185) had no significant effect on the negative conversion time of sputum smear, and there was no significant interaction between vitamin A and vitamin D supplementation. However, vitamin D supplementation significantly improved the symptoms of tuberculosis patients, and their TB-score decreased at 2 to 4 weeks (MD=-0.2，95%CI：-0.4~0）。

SARS-CoV-2 is a member of Beta-CoV lineage B and has 75% to 80% homology to the severe acute respiratory syndrome coronavirus (SARS-CoV) genome sequence. Vaccines are an effective measure to control ongoing COVID-19 and previous coronavirus infections such as MERS/SARS. Spike receptor binding domain (RBD) is an ideal target for coronavirus vaccines, but the limited immunogenicity of RBD limits vaccine development against this domain. This study found that a dimeric form of Middle East respiratory syndrome coronavirus (MERS-CoV) RBD can effectively improve RBD immunogenicity. RBD-dimer significantly increased the titer of neutralizing antibodies (NAb) and protected mice from MERS-CoV infection compared to conventional monomeric forms. Crystal structure studies revealed that the RBD-dimer completely exposed the dual receptor binding motif (the primary target of NAbs). Structure-guided design further yielded stable RBD-dimers, i.e. tandem repeating single chains (RBD-SC-dimers), preserving the efficacy of the vaccine. The researchers generalized the strategy to vaccine designs against COVID-19 and SARS, resulting in a 10-to 100-fold increase in NAb titers. The RBD-SC-dimer achieved higher yield in pilot production, which provided a theoretical basis for subsequent clinical development and application. This strategy can be generalized to design vaccines against multiple beta-CoVs, providing safeguards for controlling coronavirus infections such as SARS-CoV-2, MERS, and SARS-CoV.