[Evaluation of the efficacy of TIPS in 27 patients with hepatic sinus obstruction syndrome in the near and medium term].

Objective: intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS). Methods: A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ (2) test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results: PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt (t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt (t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion: TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.

[Analysis of 53 cases of transjugular liver biopsy].

Objective: To investigate the practicability and safety of transjugular liver biopsy (TJLB). Methods: Data of 53 cases with transjugular liver biopsy from June 2015 to June 2020 were collected. LABS-100 was used in all patients who underwent transjugular liver biopsy. Among them, 45 cases and eight were biopsied via hepatic vein and intrahepatic segment of the inferior vena cava. The surgical indications, related complications, and postoperative pathological diagnosis were analyzed and summarized. Results: TJLB was successful in all patients, with an average of 2.8 punctures per case. Satisfactory liver tissue and histopathological diagnosis was obtained in all patients. Two cases developed a cervical hematoma that was improved spontaneously, and one patient developed an intrahepatic hematoma that was improved after conservative treatment. Conclusion: TJLB is a practical and safe method for patients with contraindications to percutaneous liver biopsy.

[Study on the correlation between PPG and HVPG in patients with portal hypertension].

Objective: To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT). Methods: 752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results: Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 (P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg (P<0.001), 0.145, and 0.021 (P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 (P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion: The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

[Noninvasive assessment of the risk of esophageal variceal bleeding from noncirrhotic portal hypertension].

Objective: To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH). Methods: 111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results: Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively (P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 (P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups (P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively (P<0.05). Conclusion: Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

[Status of HVPG clinical application in China in 2021].

Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Resveratrol Promotes in vitro Differentiation of Osteoblastic MC3T3-E1 Cells via Potentiation of the Calcineurin/NFATc1 Signaling Pathway.

Resveratrol has been shown to stimulate differentiation of osteoblastic MC3T3-E1 cells in vitro; however, the mechanisms underlying the anabolic effect of resveratrol on osteoblasts remain largely unknown. Our study was aimed to investigate the molecular mechanism of resveratrol-induced differentiation of MC3T3-E1 cells. MC3T3-E1 cells were treated for 8 days with different concentrations of resveratrol (10-8-10-6 M) and 10-6 M cyclosporine A (CsA), a specific inhibitor of the calcineurin/NFAT pathway. According to the results of pilot studies of cell proliferation and alkaline phosphatase activity, 10-7 M concentration of resveratrol was used in subsequent experiments. The levels of mRNA expression of the osteosis-related genes CaN, NFATc1, and Runx2 were analyzed by real-time RT-PCR; the levels of the corresponding proteins were estimated by Western blot analysis. Resveratrol upregulated expression of the CaN, NFATc1, and Runx2 genes at both mRNA and protein levels compared to the control group (p < 0.05), while CsA reduced the effects of resveratrol (p < 0.05). Using immunohistochemical staining, we showed that resveratrol induced NFATc1 accumulation in the cell nuclei, and treatment with CsA inhibited resveratrol-mediated induction of NFATc1, suggesting that the calcineurin/NFATc1 signaling pathway plays an important role in the regulatory effect of resveratrol on osteoblasts.

[Association of single nucleotide polymorphisms of TBX5 gene and environmental exposure index with susceptibility to oral cancer].

Objective: To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods: A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results: The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (ß=-0.405, P<0.001). Conclusion: This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

Enhanced heat stable antifungal factor production by Lysobacter enzymogenes OH11 with cheap feedstocks: medium optimization and quantitative determination.

Heat stable antifungal factor (HSAF) is considered to be a potential biological pesticide due to its broad antifungal activity and novel mode of action. However, few studies have reported on HSAF production during fermentation. Thus, this work was executed to optimize the medium composition to maximize HSAF production by Lysobacter enzymogenes OH11, with soybean flour, glucose and CaCl2 identified as suitable nutrients with concentrations of 8·00, 7·89 and 0·72 g l-1 respectively. Simultaneously, the quantitative analysis of HSAF production was established by eliminating the emulsification problem, and the highest HSAF production was determined to be 356·34 ± 13·86 mg l-1 using the optimized medium, 12-fold higher than when using the 10% TSB medium (29·34 ± 2·57 mg l-1 ). Furthermore, the cost of this medium was assessed and nearly 31-fold lower than that of 10% TSB. This study suggests that the optimized medium is not only effective but also economical for HSAF production. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: Heat stable antifungal factor (HSAF) exhibits a potent and broad antifungal activity with a novel mode of action. Increased production and reduced cost of raw materials are particularly important for the future production of HSAF, however, no report was involved in these studies. This study aimed to improve the production of HSAF with cheap raw materials through the medium optimization, which would lay the foundation for the application of HSAF in biological control.

[Stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas].

Objective: To evaluate the effect of stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas. Methods: Five cases of adult thalamic high grade gliomas (WHO Ⅲ-Ⅳ) were treated with stereotactic iodine-125 brachytherapy and temozolomide chemotherapy at the Second Affiliated Hospital of Zhejiang University School of Medicine between December 2016 and February 2018, assisted with stereotactic plan and radiation therapy planning system. Results: Pathology revealed anaplastic astrocytoma (WHO Ⅲ, 2 cases) and glioblastoma (WHO Ⅳ, 3 cases). The average amount of iodine-125 implanted was 10.6 seeds. After surgery, the Karnofsky Performance Scale (KPS) was the same as preoperative KPS, and there was no severe surgery related neurological deficits. The follow-up time was from 2 months to 16 months, with an average of 7.8 months. One patient (WHO Ⅲ) without chemotherapy presented with tumor progression 6.5 months later. The other four cases showed tumor stable on MRI. Conclusions: Stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas showed satisfactory recent curative effect. Large case studies and long follow-up are needed for further evaluation.

[A case-control study: association between oral hygiene and oral cancer in non-smoking and non-drinking women].

Objective: To evaluate the influence of oral hygiene on risk of oral cancer in non-smoking and non-drinking women. Methods: From September 2010 to February 2016, 242 non-smoking and non-drinking female patients with pathologically confirmed oral cancer were recruited in a hospital of Fuzhou, and another 856 non-smoking and non-drinking healthy women from health examination center in the same hospital were selected as control group. Five oral hygiene related variables including the frequency of teeth brushing, number of teeth lost, poor prosthesis, regular dental visits and recurrent dental ulceration were used to develop oral hygiene index model. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI). The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictability of the oral hygiene index model. Multivariate logistic regression model was used to analyze the association between oral hygiene index and the incidence of oral cancer. Results: Teeth brushing <2 twice daily, teeth lost ≥5, poor prosthesis, no regular dental visits, recurrent dental ulceration were risk factors for the incidence of oral cancer in non-smoking and non-drinking women, the corresponding OR (95%CI) were 1.50 (1.08-2.09), 1.81 (1.15-2.85), 1.51 (1.03-2.23), 1.73 (1.15-2.59), 7.30 (4.00-13.30), respectively. The AUROC of the oral hygiene index model was 0.705 9, indicating a high predictability. Multivariate logistic regression showed that the oral hygiene index was associated with risk of oral cancer. The higher the score, the higher risk was observed. The corresponding OR (95%CI) of oral hygiene index scores (score 1, score 2, score 3, score 4-5) were 2.51 (0.84-7.53), 4.68 (1.59-13.71), 6.47 (2.18-19.25), 15.29 (5.08-45.99), respectively. Conclusion: Oral hygiene could influence the incidence of oral cancer in non-smoking and non-drinking women, and oral hygiene index has a certain significance in assessing the combined effects of oral hygiene.

[Pickled food, fish, seafood intakes and oral squamous cell carcinoma: a case-control study].

Objective: To investigate the effects between fish, seafood and pickled food intakes on oral squamous cell carcinoma (OSCC). Methods: A case-control study was carried out in Fujian area during September 2010 to December 2016, in which 604 newly diagnosed primary OSCC cases confirmed by pathological diagnosis were collected from hospital and 1 343 control subjects were enrolled from community and healthy hospital population. Demographic data, history of smoking drinking and tea drinking, oral hygiene status and dietary behaviors (fish, seafood and pickled food intakes) were collected by in-person interviews using a standard questionnaire.Using unconditional logistic regression to estimate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the effects of fish, seafood and pickled food intakes on OSCC. Analysis stratified by smoking, alcohol drinking and bad prosthesis to explore the possible difference in association between subgroups. Multiplicative interactions and additive interactions between fish and bad prosthesis, seafood and alcohol drinking, pickled food and bad prosthesis were assessed by unconditional logistic regression, relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). Results: The average age of case group and control group were separately (58.69±13.92) years old and (59.27±11.37) years old (χ(2)=4.75, P=0.191). The people whose fish and seafood intakes ≥3 times/week had the lower risk of OSCC, the adjusted OR (95%CI) values were 0.63 (0.52-0.77) and 0.51 (0.41-0.64); The stratified analysis indicated that the people having bad prosthesis had the lower risk of OSCC if they eating fish ≥3 times/week, and the adjusted OR (95%CI) values was 0.53 (0.39-0.71); the people having bad prosthesis had the higher risk of OSCC if they eating pickled food ≥3 times/week, the adjusted OR (95%CI) values was 1.37 (1.02-1.88). Regularly eating seafood can decrease the risk of OSCC for non-smokers, smokers, non-drinkers, drinkers, people without bad prosthesis and had bad prosthesis, the adjusted OR (95%CI) values were 0.49 (0.36-0.68), 0.52 (0.37-0.73), 0.41 (0.31-0.55), 0.77 (0.51-0.96), 0.49 (0.36-0.67), 0.59 (0.42-0.83). Crossover analysis showed fish and bad prosthesis exist multiplication interaction relationship (adjusted OR=0.66, 95%CI: 0.44-0.97) and additional interaction relationship (RERI=-0.81, 95%CI:-1.43--0.19; AP=-0.76, 95%CI:-1.35--0.17; S=0.08, 95%CI: 0.01-0.98); pickled food and bad prosthesis exist multiplication interaction relationship (adjusted OR=1.63, 95%CI: 1.06-2.51) and addition interaction relationship (RERI=0.65, 95%CI:0.08-1.22; AP=0.36, 95%CI:0.10-0.62; S=5.19, 95%CI:1.32-54.49). Conclusion: Reducing the consumption of pickled food, quitting smoking and limiting alcohol consumption, and regularly eating fish and seafood can prevent the occurrence of OSCC.

[Analysis methods and case analysis of effect modification (1): effect modification in epidemiology and traditional Meta-analysis].

This paper briefly introduces the definition, classification and significance of effect modification in epidemiological studies, summarizes the difference between effect modifier and confounders, and analyze the influence as well as the role of effect modification in epidemiological studies and Meta-analysis. In this paper, the possible scenarios of effect modification and related analysis strategy in Meta-analysis are indicated by graphics, aiming to arouse researchers' attention to effect modification. This paper also demonstrates how to identify and deal with effect modification in Meta-analysis through a study case of "Efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes", and shows the analysis process and interpretation of results of subgroup analysis and Meta-regression methods respectively. The advantages and disadvantages of these two methods are summarized to provide reference for the method selection of future research.

[Analysis methods and case analysis of effect modification (2): effect modification in network Meta-analysis].

This paper briefly introduces the characteristics, research significance, and global reporting status of effect modification in network Meta-analysis, demonstrates the heterogeneity caused by effect modification in network Meta-analysis, and emphasizes the importance of exploring effect modification in network Meta-analysis. This paper also summarizes the normalized description and analysis strategies of effect modification in network Meta-analysis. Finally, by the case of "comparison of efficacy of three new hypoglycemic drugs in reducing body weight in type 2 diabetes patients", this paper demonstrates the realization of subgroup analysis and network Meta-regression in exploring effect modification, summarizes the advantages and disadvantages of the two methods, to provide references for future researchers.

[Analysis methods and case analysis of effect modification (3): effect modification in individual patient data Meta-analysis].

This paper briefly introduces the unique advantages, overall analysis ideas and existing analysis methods of individual patient data Meta-analysis in terms of effect modification. In addition to Meta-regression and subgroup analysis, this paper also introduces the analysis methods based on part of individual patient data integrated with aggregated data and summarizes the current reporting of the above mentioned methods. In addition, the application and results interpretation of the above mentioned methods in individual patient data Meta-analysis are presented in this paper by taking "Effects of sodium-glucose cotransporter 2 inhibitors on SBP in patients with type 2 diabetes" as an example and by introducing their advantages and limitations.

First Report of Seedling Blight of Watermelon Caused by Acidovorax citrulli Transmitted from Rootstock of Pumpkin in China.

Bacterial fruit blotch (BFB) is a devastating disease caused by Acidovorax citrulli, which was first observed in the United States in 1988 (3). A. citrulli can cause severe infection on a wide range of cucurbits, including watermelon, cantaloupe, and pumpkin. Cotyledon symptoms are brown, angular, necrotic spots or large necrotic lesions. The disease is seedborne, so seeds usually serve as the primary inoculum source for BFB outbreaks (2). In July 2012, seedling blight was observed by local farmers from Anhui province in China on watermelon seedlings grafted to pumpkin rootstocks; lesions were morphologically similar to those caused by A. citrulli. Presence of A. citrulli was detected in symptomatic samples by using species-specific primers BX-L1/BX-S-R2 (1). The seed company claimed seeds of watermelon (cv. Changfeng) were certified free of bacterial fruit blotch, but pumpkin seeds (cv. Kangkuxianfeng-1) had not been tested for A. citrulli. For investigating the inoculum source, the remaining seeds of watermelon (cv. Changfeng) and pumpkin (cv. Kangkuxianfeng-1) for seedling production were collected from the farmer and processed for pathogen extraction as described by Walcott and Gitaitis (2). Two microliters of seed wash was used as template for PCR using primers BX-L1/BX-S-R2 (1). The experiment was conducted three times. A 279-bp DNA fragment was consistently amplified by PCR from seed wash of pumpkin seeds, but not from the seed wash of watermelon seeds. Three Acidovorax-like strains (A1, A2, and A3) were isolated from pumpkin seed wash using TWZ semi-selective medium (0.5% peptone, 0.025% CaCl2, 1% Tween-80, 50 mg/liter berberine, 50 mg/liter cycloheximide, 50 mg/liter 2,3,5-triphenyltetrazolium chloride). PCR was performed on the 16S rDNA gene from isolate strain A1, A2, and A3 (1,492 bp; GenBank Accession Nos. JX875533, JX875534, and JX875535) with primers rp1/fd2 (4), and PCR products were sequenced. Results of sequence analysis showed the sequences of strains A1, A2, and A3 were 99% identical to that of the type strain of A. citrulli AAC00-1 (NC_008752). Pathogencity was confirmed by injection of pumpkin cotyledons with bacterial suspensions of each isolate. Collected pumpkin seeds (n = 100 seeds) and watermelon seeds (n = 100 seeds) were planted in plastic pots containing sterilized field soil at room temperature to detect A. citrulli by a wet chamber growing out test. Eight days later, brown, angular, necrotic spots or wilt developed in pumpkin seedlings, but no symptoms were noted on the watermelon seedlings. To our knowledge, this is the first report of A. citrulli causing watermelon seedling blight transmitted from pumpkin seeds by grafting in China. References: (1) O. Bahar et al. Plant Pathol. 57:754, 2008. (2) R. R. Walcott and R. D. Gitaitis. Plant Dis. 84:470, 2000. (3) G. C. Wall et al. Phytopathology 78:1605, 1988. (4) W. G. Weisburg et al. J. Bacteriol. 173:697, 1991.

[Methods for controlling time-varying confounding in pharmaco-epidemiological studies: a systematic reveiw].

Objective: To systematically review the application of methods for controlling time-varying confounding in pharmaco-epidemiological studies. Methods: PubMed, Embase, CNKI, and Wanfang were searched for pharmaco-epidemiological studies involving time-varying confounding on June 15th, 2020. The basic characteristics, drug exposure and outcome, time-varying confounders and the application of methods to control these confounders were analyzed. Results: A total of 298 articles were included. An increasing trend was observed in numbers of studies dealing with time-varying confounding in pharmaco-epidemiological studies in recent years. A total of 106 (35.6%) studies involved the safety or effectiveness of medication use in HIV/AIDS patients and 92 of them involved antiretroviral drugs. The most common outcome was mortality, while the most commonly concerned time-dependent confounders were laboratory examination results (179, 60.1%), comorbidities (136, 45.6%), and co-used medications (108, 36.2%). Marginal structure model (MSM) and inverse probability of treatment weighting (IPTW) were the most commonly used methods to control time-varying confounding factors (244, 81.9%). Compared with the results after properly controlling time-varying confounding, traditional methods adjusting only baseline confounders resulted in substantial bias (median 18.2%, interquartile range, 7.4%-40.8%). As for basic assumptions needed for causal methods controlling time-varying confounding, 28.9% and 64.8% of the included studies examined or discussed the assumptions of positivity and no unmeasured confounders, respectively. Conclusions: At present, most of the fields of drug therapy for chronic diseases still pay insufficient attention to time-varying confoundings. Information collected in routine medical practice, such as laboratory tests, comorbidities, and co-used drugs, was the most commonly concerned time-varying confounder. MSM and IPTW were the most commonly applied methods for dealing with time-varying confounding.